PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1187859)

Clipboard (0)
None

Related Articles

1.  Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study 
PLoS Medicine  2010;7(9):e1000336.
In a retrospective cohort study, Gabriel Chodick and colleagues find a significant association between persistence with statin therapy and reduced risk of developing rheumatoid arthritis, but only a modest decrease in risk of osteoarthritis.
Background
The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA.
Methods and Findings
The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins.
A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 person-years) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of <20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52–0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81–0.88) compared to nonadherent patients.
Conclusions
The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The role of statins in the management of diseases that have an inflammatory component is unclear. There is some evidence that statins may have anti-inflammatory and immunumodulatory properties, demonstrated by reducing the level of C-reactive protein that may play an important role in chronic inflammatory diseases, such as rheumatoid arthritis—a chronic condition that is a major cause of disability. Some small studies have suggested a modest effect of statins in decreasing disease activity in patients with rheumatoid arthritis, but a recent larger study involving over 30,000 patients with rheumatoid arthritis showed no beneficial effect. Furthermore, it has been suggested that statins may have a role in the primary prevention of rheumatoid arthritis, but so far there has been no solid evidence base to support this hypothesis. Before statins can potentially be included in the treatment options for rheumatoid arthritis, or possibly prescribed for the prevention of this condition, there needs to be a much stronger evidence base, such as larger studies with longer follow-up periods, which clearly demonstrates any significant clinical benefits of statin use.
Why Was This Study Done?
This large study (more than 200,000 patients) with a long follow-up period (average of 10 years) was conducted to discover whether there was any kind of association between persistent use of statins and the onset of rheumatoid arthritis.
What Did the Researchers Do and Find?
The researchers conducted a retrospective cohort study among the members of Maccabi Healthcare Services (a health maintenance organization [HMO]) in Israel, which has 1.8-million enrollees and covers every section of the Israeli population, to identify statin users who were at least 18 years of age and did not have RA or a related disease at study entry. The cohort covered the period 1998–2007 and included members who were continuously enrolled in the HMO from 1995 to 1998. The researchers then analyzed the incidence of newly diagnosed rheumatoid arthritis, recording the date of first diagnostic codes (International Classification of Diseases, 9th revision [ICD-9]) associated with rheumatoid arthritis during the study follow-up period. To assess any potential effects of “healthy adherer” bias (good adherence to medication in patients with a chronic illness may be more likely to lead to better health and improved survival), the researchers also examined any possible association between persistent statin use and the development of osteoarthritis, a common degenerative joint disease that is unlikely to be affected by statin use.
During the study follow-up period, there were 2,578 incident cases of rheumatoid arthritis and 17,878 incident cases of osteoarthritis. The crude incidence density rate of rheumatoid arthritis among patients who did not persistently take statins was 51% higher than that of patients who used statins for at least 80% of the follow-up period. Furthermore, patients who persistently used statins had a risk ratio of 0.58 for rheumatoid arthritis compared with patients who did not persistently use statins. In the osteoarthritis cohort analysis, high persistence with statin use was associated with a modest decrement in risk ratio (0.85) compared to patients who did not persist with statins.
What Do These Findings Mean?
This study suggests that there is an association between persistence with statin therapy and reduced risk of developing rheumatoid arthritis. Although the researchers took into account the possibility of healthy adherer bias (by comparing results with the osteoarthritis cohort), this study has other limitations, such as the retrospective design, and the nonrandomization of statin use, which could affect the interpretation of the results. However, the observed associations were greater than those that would be expected from methodological biases alone. Larger, systematic, controlled, prospective studies with high efficacy statins, particularly in younger adults who are at increased risk for rheumatoid arthritis, are needed to confirm these findings and to clarify the exact nature of the biological relationship between adherence to statin therapy and the incidence of rheumatoid arthritis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000336.
Arthritis Research UK provides a wide range of information on arthritis research
The American College of Rheumatology provides information on rheumatology research
Patient information on rheumatoid arthritis is available at Patient UK
Extensive information about statins is available at statin answers
doi:10.1371/journal.pmed.1000336
PMCID: PMC2935457  PMID: 20838658
2.  Is statin discontinuation an option in patients who have had a stroke? 
SYNOPSIS
BACKGROUND
There is clear evidence that long-term statin therapy can prevent the recurrence of vascular events, but in clinical practice, many patients discontinue statin therapy.
OBJECTIVE
To evaluate the effect of statin interruption on clinical outcome in patients discharged after an acute ischemic stroke.
DESIGN AND INTERVENTION
The present study was conducted at an Italian community hospital and enrolled consecutive stroke patients who were discharged from January 2000 to June 2005. Inclusion criteria were absence of any major concurrent illness, absence of any clinical and laboratory evidence of coronary heart disease (CHD) or of any other major cardiac affect or cardiac embolism, and discharge on statin therapy. After exclusions, 631 patients (51% male; mean ± SD age 70.2 ± 7.6 years) were enrolled. All participants were followed up for 12 months. Adherence to prescribed medications was evaluated by telephone interview at 1, 6 and 12 months after discharge. Switching from one cardiovascular agent to another of the same class was considered adherence to the prescribed therapy. Univariate and multivariate Cox proportionalhazards regression analyses were performed to identify risk factors for occurrence of the primary end point, and to identify clinical and demographic variables associated with statin therapy discontinuation during the follow-up period.
OUTCOME MEASURES
The primary end point was death from any cause within 12 months of discharge.
RESULTS
At discharge, 409 (77.6%) patients received a prescription for atorvastatin and 222 (22.4%) patients received a prescription for simvastatin. During the follow-up period, 246 (38.9%) patients discontinued statin therapy; the discontinuation rates were similar for both statins (P=0.544). Seventy-one (28.8%) patients stated mild adverse effects—such as dyspepsia, fatigue, headache and myalgia—as the reason for statin interruption. No instance of major adverse event was reported. In the remaining 175 (71.2%) cases, neither the patient nor the primary care physician could provide any specific medical reason for statin discontinuation. Multivariate analysis identified increasing age (hazard ratio [HR] 1.006 per year, 95% CI 1.004-1.009; P= 0.01) and female sex (HR 1.07, 95% CI 1.03-1.11; P= 0.02) as risk factors for statin discontinuation. By contrast, patients with diabetes were more likely to continue statin therapy (HR 0.86, 95% CI 0.79-0.91; P=0.03). A total of 116 patients died within 1 year of discharge. Ninety-two (79.3%) of these patients had discontinued statin therapy compared with 154 (29.9%) patients who survived (P=0.0001), and statin interruption was identified as an independent predictor of 12-month all-cause mortality (HR 2.78, 95% CI 1.96-3.72; P=0.003). Other independent predictors of death within the first year after the stroke event were increased age, obesity, diabetes, stroke severity on admission, and antiplatelet therapy discontinuation.
CONCLUSION
A considerable proportion of patients with acute ischemic stroke are at increased risk of death within the first year after the index event because they discontinue statin therapy, often without a specific medical reason.
doi:10.1038/ncpneuro0687
PMCID: PMC2615565  PMID: 18059384
coronary heart disease; death; statins; stroke; treatment discontinuation
3.  Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study 
PLoS Medicine  2012;9(12):e1001361.
In a modeling study conducted by Myriam Hunink and colleagues, a population-based cohort from Rotterdam is used to predict the possible lifetime benefits of statin therapy, on a personalized basis.
Background
Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks.
Methods and Findings
A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk.
Conclusions
We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Cardiovascular disease (CVD) affects the heart and/or the blood vessels and is a major cause of illness and death worldwide. In the US, for example, coronary heart disease—a CVD in which narrowing of the heart's blood vessels by fatty deposits slows the blood supply to the heart and may eventually cause a heart attack—is the leading cause of death, and stroke—a CVD in which the brain's blood supply is interrupted—is the fourth leading cause of death. Established risk factors for CVD include smoking, high blood pressure, obesity, and high blood levels of a fat called low-density lipoprotein (“bad cholesterol”). Because many of these risk factors can be modified by lifestyle changes and by drugs, CVD can be prevented. Thus, physicians can assess a healthy individual's risk of developing CVD using a CVD prediction model (equations that take into account the CVD risk factors to which the individual is exposed) and can then recommend lifestyle changes and medications to reduce that individual's CVD risk.
Why Was This Study Done?
Current guidelines recommend that asymptomatic (healthy) individuals whose likely CVD risk is high should be encouraged to take statins—cholesterol-lowering drugs—as a preventative measure. Statins help to prevent CVD in healthy people with a high predicted risk of CVD, but, like all medicines, they have some unwanted side effects, so it is important that physicians can communicate both the benefits and drawbacks of statins to their patients in a way that allows them to make an informed decision about taking these drugs. Telling a patient that statins will reduce his or her short-term risk of CVD is not always helpful—patients really need to know the potential lifetime benefits of statin therapy. That is, they need to know how much longer they might live if they take statins. Here, the researchers use a mathematical model to predict the personalized lifetime benefits (increased total and CVD-free life expectancy) of statin therapy for individuals without a history of CVD.
What Did the Researchers Do and Find?
The researchers used the Rotterdam Ischemic Heart Disease & Stroke Computer Simulation (RISC) model, which simulates the life courses of individuals through six health states, from well through to CVD or non-CVD death, to estimate lifetime outcomes with and without statin therapy in a population of healthy elderly individuals. They then used these outcomes and information on baseline risk factors to develop a web-based calculator suitable for personalized prediction of the lifetime benefits of statins in routine clinical practice. The model estimated that statin therapy increases average life expectancy in the study population by 0.3 years and average CVD-free life expectancy by 0.7 years. The gains in total and CVD-free life expectancy associated with statin therapy increased with blood pressure, unfavorable cholesterol levels, and body mass index (an indicator of body fat) but decreased with age. Notably, the web-based calculator predicted that some individuals with a low ten-year CVD risk might achieve a similar or larger gain in CVD-free life expectancy with statin therapy than some individuals with a high ten-year risk. So, for example, both a 55-year-old non-smoking woman with a ten-year CVD mortality risk of 2% (a two in a hundred chance of dying of CVD within ten years) and a 65-year-old male smoker with a ten-year CVD mortality risk of 15% might both gain one year of CVD-free life expectancy with statin therapy.
What Do These Findings Mean?
These findings suggest that statin therapy can lead on average to small gains in total life expectancy and slightly larger gains in CVD-free life expectancy among healthy individuals, and show that life expectancy benefits can be predicted using an individual's risk factor profile. The accuracy and generalizability of these findings is limited by the assumptions included in the model (in particular, the model did not allow for the known side effects of statin therapy) and by the data fed into it—importantly, the risk prediction model needs to be validated using an independent dataset. If future research confirms the findings of this study, the researchers' web-based calculator could provide complementary information to the currently recommended ten-year CVD mortality risk assessment. Whether communication of personalized outcomes will ultimately result in better clinical outcomes remains to be seen, however, because patients may be less likely to choose statin therapy when provided with more information about its likely benefits.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001361.
The web-based calculator for personalized prediction of lifetime benefits with statin therapy is available (after agreement to software license)
The American Heart Association provides information about many types of cardiovascular disease for patients, carers, and professionals, including information about drug therapy for cholesterol and a heart attack risk calculator
The UK National Health Service Choices website provides information about cardiovascular disease and about statins
Information is available from the British Heart Foundation on heart disease and keeping the heart healthy; information is also available on statins, including personal stories about deciding to take statins
The US National Heart Lung and Blood Institute provides information on a wide range of cardiovascular diseases
The European Society of Cardiology's cardiovascular disease risk assessment model (SCORE) is available
MedlinePlus provides links to many other sources of information on heart diseases, vascular diseases, stroke, and statins (in English and Spanish)
doi:10.1371/journal.pmed.1001361
PMCID: PMC3531501  PMID: 23300388
4.  Statins do not prevent acute organ failure in ventilated ICU patients: single-centre retrospective cohort study 
Critical Care  2011;15(1):R74.
Introduction
Observational studies suggest statin therapy reduces incident sepsis, but few studies have examined the impact on new organ failure. We tested the hypothesis that statin therapy, administered for standard clinical indications to ventilated intensive care unit patients, prevents acute organ failure without harming the liver.
Methods
We performed a retrospective, single-centre cohort study in a tertiary mixed medical/surgical intensive care unit. Mechanically ventilated patients without nonrespiratory organ failure within 24 hours after admission were assessed (during the first 15 days) for new acute organ failure (defined as Sequential Organ Failure Assessment (SOFA) score 3 or 4), liver failure (defined as new hepatic SOFA ≥3, or a 1.5 times increase of bilirubin from baseline to a value ≥20 mmol/l), and alanine transferase (ALT) > 165 IU/l. The effect of statin administration was explored in generalised linear mixed models.
Results
A total of 1,397 patients were included. Two hundred and nineteen patients received a median (interquartile range) of three (two, eight) statin doses. Patients receiving statins were older (67.4 vs. 55.5 years, P < 0.0001), less likely female (25.1% vs. 37.9%, P = 0.0003) and sicker (Acute Physiology and Chronic Health Evaluation (APACHE) II score 20.3 vs. 17.8, P < 0.0001). Considering outcome events at least 1 day after statin administration, statin patients were equally likely to develop acute organ failure (28.4% vs. 22.3%, P = 0.29) and hepatic failure (9.5% vs. 7.6%, P = 0.34), but were more likely to experience an ALT increase to > 165 IU/l ((11.2% vs. 4.8%, P = 0.0005). Multivariable analysis showed that APACHE II score (odds ratio (OR) = 1.05 per point; 95% confidence interval (CI) = 1.03 to 1.07) and APACHE II admission category (P < 0.0001), but not statin administration (OR = 1.21; 95% CI = 0.92 to 1.62), were significantly associated with acute organ failure occurring on or after the day of first statin administration. Statin administration was not associated with liver impairment (OR = 1.08; 95% CI = 0.66 to 1.77) but was associated with a rise in ALT > 165 IU/l (OR = 2.25; 95% CI = 1.32 to 3.84), along with APACHE II score (P = 0.016) and admission ALT (P = 0.0001).
Conclusions
Concurrent statin therapy does not appear to protect against the development of new acute organ failure in critically ill, ventilated patients. The lack of effect may be due to residual confounding, a relatively low number of doses received, or an absence of true effect. Randomised controlled trials are needed to confirm a protective effect.
doi:10.1186/cc10063
PMCID: PMC3222007  PMID: 21356051
5.  Effect of Statins on Venous Thromboembolic Events: A Meta-analysis of Published and Unpublished Evidence from Randomised Controlled Trials 
PLoS Medicine  2012;9(9):e1001310.
A systematic review and meta-analysis conducted by Kazem Rahimi and colleagues re-evaluates the hypothesis, generated in previous studies, that statins may reduce the risk of venous thromboembolic events. Their meta-analysis does not support the previous findings.
Background
It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins.
Methods and Findings
We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out.
Please see later in the article for the Editors' Summary.
Conclusions
The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out.
Editors' Summary
Background
Blood normally flows smoothly throughout the human body, supplying its organs and tissues with oxygen and nutrients. But, when an injury occurs, proteins called clotting factors make the blood gel (coagulate) at the injury site. The resultant blood clot (thrombus) plugs the wound and prevents blood loss. Occasionally, however, a thrombus forms inside an uninjured blood vessel and partly or completely blocks the blood flow. A clot inside one of the veins (vessels that take blood towards the heart) deep within the body is called a deep vein thrombosis (DVT). Symptoms of DVT (which usually occurs in the leg) include pain, swelling, and redness in the affected limb. DVT is treated with heparin and warfarin, two anticoagulant drugs that stop the blood clot growing. If left untreated, part of the clot (an embolus) can break off and travel to the lungs, where it can cause a pulmonary embolism (PE), a life-threatening condition characterized by chest pain, breathlessness, coughing, and dizziness. Little is known about how to prevent DVTs and PEs but risk factors for these venous thromboembolic events include having an inherited blood clotting disorder, oral contraceptive use, having surgery, and prolonged inactivity (on long-haul plane flights, for example).
Why Was This Study Done?
In 2009, a secondary (add-on) analysis of data from a randomized controlled trial (RCT, a study that randomly assigns individuals to receive different treatments and compares the outcomes associated with each treatment) called the JUPITER trial reported that rosuvastatin—a cholesterol-lowering drug (statin)—halved the risk of venous thromboembolic events among apparently healthy adults. The JUPITER trial was initiated to test whether statins reduce the risk of strokes, heart attacks, and other cardiovascular diseases (conditions that involve the heart and the blood vessels) among adults with raised levels of a predictor for these diseases called C-reactive protein; statins reduce the levels of this protein as well as those of cholesterol. Because fewer than 100 of the participants in the JUPITER trial developed a DVT or PE, the reduction in the risk of a venous thromboembolic event among the participants who took rosuvastatin could have happened by chance. In this systematic review and meta-analysis of 29 RCTs of statins that collected information on many more venous thromboembolic events, the researchers test the hypothesis that statins substantially reduce the risk of such events. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis is a statistical approach that combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 22 RCTs (105,759 participants) that compared the effects of statins with control (dummy) tablets and seven (40,594 participants) that compared an intensive statin regimen with a standard regimen. They then obtained largely unpublished information about the venous thromboembolic events that occurred during these trials (about 1,000 DVTs and PEs) from the original investigators. In the trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events. Thus, although events occurred in 465 participants who were given statins (0.9% of the participants) and in 521 participants who were given control tablets (1% of the participants), this difference in outcomes was not statistically significant—it could have happened by chance. Exclusion of the JUPITER trial results from the meta-analysis did not alter this finding. The researchers also found no evidence that intensive statin therapy reduced the risk of venous thromboembolic events compared to standard therapy.
What Do These Findings Mean?
The findings of this meta-analysis do not support the suggestion that statins, either at the standard dose or at higher doses, reduce the risk of venous thromboembolic events substantially among healthy adults. It is possible that the effect of statins has been underestimated in this meta-analysis because of missing data or because of some other source of bias. Furthermore, because the total number of events in this meta-analysis is still relatively modest, these findings do not rule out the possibility that statins may reduce the risk of venous thromboembolic events by up to about one-fifth in some or all individuals. Additional large RCTs are now needed to investigate whether statin treatment does in fact reduce the risk of venous thromboembolic events in adults and, if it does, whether all statins have a similar effect and whether statin treatment is beneficial in everyone or only in specific subgroups of people.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001310.
This study is further discussed in a PLOS Medicine Perspective by Frits Rosendaal
The US National Heart Lung and Blood Institute provides information on deep vein thrombosis (including an animation about how DVT causes pulmonary embolisms), and information on pulmonary embolism
The UK National Health Service Choices website has information on deep vein thrombosis, including personal stories, on pulmonary embolism, and on statins; a Behind the Headlines article describes the JUPITER trial and its implications
The non-profit organization US National Blood Clot Alliance provides detailed information about deep vein thrombosis and pulmonary embolism for patients and professionals and includes a selection of personal stories about these conditions
MedlinePlus has links to further information about deep vein thrombosis, pulmonary embolism, and statins (in English and Spanish)
doi:10.1371/journal.pmed.1001310
PMCID: PMC3445446  PMID: 23028261
6.  Statins in the Treatment of Chronic Heart Failure: A Systematic Review 
PLoS Medicine  2006;3(8):e333.
Background
The efficacy of statin therapy in patients with established chronic heart failure (CHF) is a subject of much debate.
Methods and Findings
We conducted three systematic literature searches to assess the evidence supporting the prescription of statins in CHF. First, we investigated the participation of CHF patients in randomized placebo-controlled clinical trials designed to evaluate the efficacy of statins in reducing major cardiovascular events and mortality. Second, we assessed the association between serum cholesterol and outcome in CHF. Finally, we evaluated the ability of statin treatment to modify surrogate endpoint parameters in CHF.
Using validated search strategies, we systematically searched PubMed for our three queries. In addition, we searched the reference lists from eligible studies, used the “see related articles” feature for key publications in PubMed, consulted the Cochrane Library, and searched the ISI Web of Knowledge for papers citing key publications.
Search 1 resulted in the retrieval of 47 placebo-controlled clinical statin trials involving more than 100,000 patients. CHF patients had, however, been systematically excluded from these trials. Search 2 resulted in the retrieval of eight studies assessing the relationship between cholesterol levels and outcome in CHF patients. Lower serum cholesterol was consistently associated with increased mortality. Search 3 resulted in the retrieval of 18 studies on the efficacy of statin treatment in CHF. On the whole, these studies reported favorable outcomes for almost all surrogate endpoints.
Conclusions
Since CHF patients have been systematically excluded from randomized, controlled clinical cholesterol-lowering trials, the effect of statin therapy in these patients remains to be established. Currently, two large, randomized, placebo-controlled statin trials are under way to evaluate the efficacy of statin treatment in terms of reducing clinical endpoints in CHF patients in particular.
A systematic review found that patients with heart failure have been excluded from randomised controlled trials on the use of statins. Evidence from other studies on the effectiveness of statins for patients with heart failure is weak and conflicting.
Editors' Summary
Background.
When medical researchers test a drug—or some other treatment—for a particular medical condition, they often decide not to include in their study anyone who has, in addition to the disease they are interested in, certain other health problems. This is because including patients with two or more conditions can complicate the analysis of the results and make it hard to reach firm conclusions. However, excluding patients in this way can result in uncertainty as to whether treatments are effective for anyone who suffers from the disease in question, or just for people like those who took part in the research.
A great deal of research has been conducted with drugs known as statins, which lower cholesterol levels in the blood. (A raised level of cholesterol is known to be a major risk factor for cardiovascular disease, which causes heart attacks and strokes.) As a result of this research, statins have been accepted as effective and safe. They are now, in consequence, among the most commonly prescribed medicines. Heart failure, however, is not the same thing as a heart attack. It is the name given to the condition where the muscles of the heart have become weakened, most often as a result of aging, and the heart becomes gradually less efficient at pumping blood around the body. (Some people with heart failure live for many years, but 70% of those with the condition die within ten years.) It is common for people with cardiovascular disease also to have heart failure. Nevertheless, some researchers who have studied the effects of statins have made the decision not to include in their studies any patients with cardiovascular disease who, in addition, have heart failure.
Why Was This Study Done?
The researchers in this study were aware that patients with heart failure have often been excluded from statin trials. They felt it was important to assess the available evidence supporting the prescription of statins for such patients. Specifically, they wanted to find out the following: how often have patients with heart failure been included in statin trials, what evidence is available as to whether it is beneficial for patients with heart failure to have low cholesterol, and what evidence is there that prescribing statins helps these patients?
What Did the Researchers Do and Find?
They did not do any new work involving patients. Instead, they did a very thorough search for all relevant studies of good quality that had already been published and they reviewed the results. “Randomized clinical trials” (RCTs) are the most reliable type of medical research. The researchers found there had been 47 such trials (involving over 100,000 patients) on the use of statins for treating cardiovascular disease, but all these trials had excluded heart failure patients. They found eight studies (which were not RCTs) looking at cholesterol levels and heart failure. These studies found, perhaps surprisingly, that death rates were higher in those patients with heart failure who had low cholesterol. However, they also found 18 studies (again not RCTs) on the use of statins in patients with heart failure. These 18 studies seemed to suggest that statins were of benefit to the patients who received them.
What Do These Findings Mean?
The evidence for or against prescribing statins for people with heart failure is limited, conflicting, and unclear. Further research involving RTCs is necessary. (Two such trials are known to be in progress.)
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030333.
General information about statins is available from the Web site of Patient UK
The American Heart Association Web site is a good source of information about all types of heart disease, including heart attacks and heart failure
For a definition of randomized controlled trials see Wikipedia, a free online encyclopedia that anyone can edit
More detailed information about the quality of evidence from medical research may be found in the James Lind Library
doi:10.1371/journal.pmed.0030333
PMCID: PMC1551909  PMID: 16933967
7.  A cluster randomized trial to assess the impact of opinion leader endorsed evidence summaries on improving quality of prescribing for patients with chronic cardiovascular disease: rationale and design [ISRCTN26365328] 
Background
Although much has been written about the influence of local opinion leaders on clinical practice, there have been few controlled studies of their effect, and almost none have attempted to change prescribing in the community for chronic conditions such as heart failure (HF) or ischemic heart disease (IHD). These two conditions are common and there is very good evidence about how to best prevent morbidity and mortality – and good evidence that quality of care is, in general, suboptimal. Practice audits have demonstrated that about one-half of eligible HF patients are prescribed ACE inhibitors (with fewer still reaching appropriate target doses) and less than one-third of patients with established IHD are prescribed statins (with many fewer reaching recommended cholesterol targets). It is apparent that interventions to improve quality of prescribing are urgently needed. We hypothesized that an intervention that consisted of patient-specific one-page evidence summaries, generated and then endorsed by local opinion leaders, would be able to change prescribing practices of community-based primary care physicians.
Methods (study design)
A pragmatic single-centre cluster randomized controlled trial comparing an opinion leader-based intervention to usual care for patients with HF or IHD. Randomization will be clustered at the level of the primary care physician; as the design effect is anticipated to be negligible, the unit of analysis will be the patient. Patients with HF or IHD (not receiving ACE inhibitors or statins, respectively) will be recruited from community pharmacies and allocated to intervention or usual care based on the randomization status of their primary care physician. The primary outcome is improvement in prescription of proven efficacious therapies for HF (ACE inhibitors) or IHD (statins) within 6 months of the intervention.
Conclusion
If the methods used in this intervention are found to improve prescribing practices, similar interventions could be designed for other chronic conditions dealt with in the outpatient setting.
doi:10.1186/1471-2261-5-17
PMCID: PMC1175844  PMID: 15982421
8.  Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others 
PLoS Medicine  2007;4(6):e184.
Background
Published pharmaceutical industry–sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drug over placebo. Little is known about potential biases in drug–drug comparisons. This study examined associations between research funding source, study design characteristics aimed at reducing bias, and other factors that potentially influence results and conclusions in randomized controlled trials (RCTs) of statin–drug comparisons.
Methods and Findings
This is a cross-sectional study of 192 published RCTs comparing a statin drug to another statin drug or non-statin drug. Data on concealment of allocation, selection bias, blinding, sample size, disclosed funding source, financial ties of authors, results for primary outcomes, and author conclusions were extracted by two coders (weighted kappa 0.80 to 0.97). Univariate and multivariate logistic regression identified associations between independent variables and favorable results and conclusions. Of the RCTs, 50% (95/192) were funded by industry, and 37% (70/192) did not disclose any funding source. Looking at the totality of available evidence, we found that almost all studies (98%, 189/192) used only surrogate outcome measures. Moreover, study design weaknesses common to published statin–drug comparisons included inadequate blinding, lack of concealment of allocation, poor follow-up, and lack of intention-to-treat analyses. In multivariate analysis of the full sample, trials with adequate blinding were less likely to report results favoring the test drug, and sample size was associated with favorable conclusions when controlling for other factors. In multivariate analysis of industry-funded RCTs, funding from the test drug company was associated with results (odds ratio = 20.16 [95% confidence interval 4.37–92.98], p < 0.001) and conclusions (odds ratio = 34.55 [95% confidence interval 7.09–168.4], p < 0.001) that favor the test drug when controlling for other factors. Studies with adequate blinding were less likely to report statistically significant results favoring the test drug.
Conclusions
RCTs of head-to-head comparisons of statins with other drugs are more likely to report results and conclusions favoring the sponsor's product compared to the comparator drug. This bias in drug–drug comparison trials should be considered when making decisions regarding drug choice.
Lisa Bero and colleagues found published trials comparing one statin with another were more likely to report results and conclusions favoring the sponsor's product than the comparison drug.
Editors' Summary
Background.
Randomized controlled trials are generally considered to be the most reliable type of experimental study for evaluating the effectiveness of different treatments. Randomization involves the assignment of participants in the trial to different treatment groups by the play of chance. Properly done, this procedure means that the different groups are comparable at outset, reducing the chance that outside factors could be responsible for treatment effects seen in the trial. When done properly, randomization also ensures that the clinicians recruiting participants into the trial cannot know the treatment group to which a patient will end up being assigned. However, despite these advantages, a large number of factors can still result in bias creeping in. Bias comes about when the findings of research appear to differ in some systematic way from the true result. Other research studies have suggested that funding is a source of bias; studies sponsored by drug companies seem to more often favor the sponsor's drug than trials not sponsored by drug companies
Why Was This Study Done?
The researchers wanted to more precisely understand the impact of different possible sources of bias in the findings of randomized controlled trials. In particular, they wanted to study the outcomes of “head-to-head” drug comparison studies for one particular class of drugs, the statins. Drugs in this class are commonly prescribed to reduce the levels of cholesterol in blood amongst people who are at risk of heart and other types of disease. This drug class is a good example for studying the role of bias in drug–drug comparison trials, because these trials are extensively used in decision making by health-policy makers.
What Did the Researchers Do and Find?
This research study was based on searching PubMed, a biomedical literature database, with the aim of finding all randomized controlled trials of statins carried out between January 1999 and May 2005 (reference lists also were searched). Only trials which compared one statin to another statin or one statin to another type of drug were included. The researchers extracted the following information from each article: the study's source of funding, aspects of study design, the overall results, and the authors' conclusions. The results were categorized to show whether the findings were favorable to the test drug (the newer statin), inconclusive, or not favorable to the test drug. Aspects of each study's design were also categorized in relation to various features, such as how well the randomization was done (in particular, the degree to which the processes used would have prevented physicians from knowing which treatment a patient was likely to receive on enrollment); whether all participants enrolled in the trial were eventually analyzed; and whether investigators or participants knew what treatment an individual was receiving.
One hundred and ninety-two trials were included in this study, and of these, 95 declared drug company funding; 23 declared government or other nonprofit funding while 74 did not declare funding or were not funded. Trials that were properly blinded (where participants and investigators did not know what treatment an individual received) were less likely to have conclusions favoring the test drug. However, large trials were more likely to favor the test drug than smaller trials. When looking specifically at the trials funded by drug companies, the researchers found various factors that predicted whether a result or conclusion favored the test drug. These included the impact of the journal publishing the results; the size of the trial; and whether funding came from the maker of the test drug. However, properly blinded trials were less likely to produce results favoring the test drug. Even once all other factors were accounted for, the funding source for the study was still linked with results and conclusions that favored the maker of the test drug.
What Do These Findings Mean?
This study shows that the type of sponsorship available for randomized controlled trials of statins was strongly linked to the results and conclusions of those studies, even when other factors were taken into account. However, it is not clear from this study why sponsorship has such a strong link to the overall findings. There are many possible reasons why this might be. Some people have suggested that drug companies may deliberately choose lower dosages for the comparison drug when they carry out “head-to-head” trials; this tactic is likely to result in the company's product doing better in the trial. Others have suggested that trials which produce unfavorable results are not published, or that unfavorable outcomes are suppressed. Whatever the reasons for these findings, the implications are important, and suggest that the evidence base relating to statins may be substantially biased.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040184.
The James Lind Library has been created to help people understand fair tests of treatments in health care by illustrating how fair tests have developed over the centuries
The International Committee of Medical Journal Editors has provided guidance regarding sponsorship, authorship, and accountability
The CONSORT statement is a research tool that provides an evidence-based approach for reporting the results of randomized controlled trials
Good Publication Practice guidelines provide standards for responsible publication of research sponsored by pharmaceutical companies
Information from Wikipedia on Statins. Wikipedia is an internet encyclopedia anyone can edit
doi:10.1371/journal.pmed.0040184
PMCID: PMC1885451  PMID: 17550302
9.  Discontinuation of statin therapy in older people: does a cancer diagnosis make a difference? An observational cohort study using data linkage 
BMJ Open  2012;2(3):e000880.
Objective
The aim was to examine statin discontinuation rates in a cohort of elderly Australians with newly diagnosed cancer using population-based secondary health data.
Design
Observational cohort study.
Setting
New South Wales, the largest jurisdiction in Australia. The Pharmaceutical Benefits and Repatriation Pharmaceutical Benefits Schemes are national programmes subsidising prescription drugs to the Australian population and Australian Government Department of Veterans' Affairs clients.
Participants
The cohort comprised 1731 cancer patients aged ≥65 years with evidence of statin use in the 90 days prior to diagnosis. They were matched to 3462 non-cancer patients prescribed statins in the same period.
Main outcome measure
The authors compared statin discontinuation rates up to 4 years post-diagnosis and examined the factors associated with statin discontinuation.
Results
The proportion of cancer patients discontinuing statin therapy at 4 years (27%) was comparable to the comparison cohort; however, significantly higher proportions of the cancer cohort discontinued statins than the comparison cohort at 3, 6 and 12 months of follow-up (9.7% vs 7.4% at 12 months, respectively). More than 30% of cancer patients who died were dispensed statins within 30 days of death. Discontinuation of statin therapy in cancer patients was associated with regionalised and distant disease spread at diagnosis (p<0.001), older age (p=0.006), upper gastrointestinal organs and liver cancer (aHR 2.95, 95% CI 1.92 to 4.53) and cancer of the lung, bronchus and trachea (aHR 1.99, 95% CI 1.32 to 3.00) and poorer survival.
Conclusions
Medications should be rationalised at the time of a cancer diagnosis, especially in the setting of a poor prognosis. At least for some patients in our cohort, statin therapy may be inappropriately continued which adds unnecessarily to therapeutic burden.
Article summary
Article focus
There is limited clinical guidance on managing comorbid conditions after the diagnosis of life-threatening illness.
Some medications may be continued unnecessarily and may even cause harm after a cancer diagnosis.
The aim of this study is to examine the rates of statin discontinuation in a cohort of older cancer patients compared with their peers with no cancer diagnosis.
Key messages
In the setting of cancer, statins may be continued unnecessarily in some patients.
A high proportion of cancer patients are dispensed statins 30 days before death.
Reassessment of existing treatments is recommended after a cancer diagnosis so as to minimised therapeutic burden.
Strengths and limitations of this study
This is a large retrospective cohort study of elderly Australians using population data set linkage.
We were unable to establish if statin therapy had been reviewed subsequent to a cancer diagnosis nor the reasons for discontinuation.
doi:10.1136/bmjopen-2012-000880
PMCID: PMC3358623  PMID: 22614172
10.  The efficiency of cardiovascular risk assessment: do the right patients get statin treatment? 
Heart  2013;99(21):1597-1602.
Objective
To evaluate targeting of statin prescribing for primary prevention to those with high cardiovascular disease (CVD) risk.
Design
Two cohort studies including the general population and initiators of statins aged 35–74 years.
Setting
UK primary care records in the Clinical Practice Research Datalink.
Patients
3.8 million general population patients and 300 914 statin users.
Intervention
Statin prescribing.
Main outcome measures
Statin prescribing by CVD risk; observed 5-year CVD risks; variability between practices.
Results
Statin prescribing increased substantially over time to patients with high 10-year CVD risk (≥20%): 7.0% of these received a statin prior to 2007, and 30.4% in 2007 onwards. Prescribing to patients with low risk (<15%) also increased (from 1.9% to 5.0%). Only about half the patients initiating statin treatment were high risk according to CVD risk score. The 5-year CVD risks, as observed during statin treatment, reduced over calendar time (from 17.0% to 7.1%). There was a large variation between general practices in the percentage of high-risk patients prescribed a statin in 2007 onwards, ranging from 8.2% to 61.5%. For low-risk patients, these varied from 2.1% to 29.1%.
Conclusions
There appeared to be substantive overuse in low CVD risk and underuse in high CVD risk (600 000 and 850 000 patients, respectively, in the UK since 2007). There is wide variation between practices in statin prescribing to patients at high CVD risk. There is a clear need for randomised trials for the best strategy to target statin treatment and manage CVD risk for primary prevention.
doi:10.1136/heartjnl-2013-303698
PMCID: PMC3812879  PMID: 23735939
11.  Glycaemic control in Australia and New Zealand before and after the NICE-SUGAR trial: a translational study 
Critical Care  2013;17(5):R215.
Introduction
There is no information on the uptake of Intensive Insulin Therapy (IIT) before the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and New Zealand (ANZ) and on the bi-national response to the trial, yet such data would provide important information on the evolution of ANZ practice in this field. We aimed to study ANZ glycaemic control before and after the publication of the results of the NICE-SUGAR trial.
Methods
We analysed glucose control in critically ill patients across Australia and New Zealand during a two-year period before and after the publication of the NICE-SUGAR study. We used the mean first day glucose (Glu1) (a validated surrogate of ICU glucose control) to define practice. The implementation of an IIT protocol was presumed if the median of Glu1 measurements was <6.44 mmol/L for a given ICU. Hypoglycaemia was categorised as severe (glucose ≤2.2 mmol/L) or moderate (glucose ≤3.9 mmol/L).
Results
We studied 49 ICUs and 176,505 patients. No ICU practiced IIT before or after NICE-SUGAR. Overall, Glu1 increased from 7.96 (2.95) mmol/L to 8.03 (2.92) mmol/L (P <0.0001) after NICE-SUGAR. Similar increases were noted in all patient subgroups studied (surgical, medical, insulin dependent diabetes mellitus, ICU stay >48/<48 hours). The rate of severe and moderate hypoglycaemia before and after NICE-SUGAR study were 0.59% vs. 0.55% (P =0.33) and 6.62% vs. 5.68% (P <0.0001), respectively. Both crude and adjusted mortalities declined over the study period.
Conclusions
IIT had not been adopted in ANZ before the NICE-SUGAR study and glycaemic control corresponded to that delivered in the control arm of NICE-SUGAR trial. There were only minor changes in practice after the trial toward looser glycaemic control. The rate of moderate hypoglycaemia and mortality decreased along with such changes.
doi:10.1186/cc13030
PMCID: PMC4056083  PMID: 24088368
12.  Is the high-risk strategy to prevent cardiovascular disease equitable? A pharmacoepidemiological cohort study 
BMC Public Health  2012;12:610.
Background
Statins are increasingly prescribed to prevent cardiovascular disease (CVD) in asymptomatic individuals. Yet, it is unknown whether those at higher CVD risk – i.e. individuals in lower socio-economic position (SEP) – are adequately reached by this high-risk strategy. We aimed to examine whether the Danish implementation of the strategy to prevent cardiovascular disease (CVD) by initiating statin (HMG-CoA reductase inhibitor) therapy in high-risk individuals is equitable across socioeconomic groups.
Methods
Design: Cohort study.
Setting and participants: Applying individual-level nationwide register information on socio-demographics, dispensed prescription drugs and hospital discharges, all Danish citizens aged 20+ without previous register-markers of CVD, diabetes or statin therapy were followed during 2002–2006 for first occurrence of myocardial infarction (MI) and a dispensed statin prescription (N = 3.3 mill).
Main outcome measures: Stratified by gender, 5-year age-groups and socioeconomic position (SEP), incidence of MI was applied as a proxy for statin need. Need-standardized statin incidence rates were calculated, applying MI incidence rate ratios (IRR) as need-weights to adjust for unequal needs across SEP.Horizontal equity in initiating statin therapy was tested by means of Poisson regression analysis. Applying the need-standardized statin parameters and the lowest SEP-group as reference, a need-standardized statin IRR > 1 translates into horizontal inequity favouring the higher SEP-groups.
Results
MI incidence decreased with increasing SEP without a parallel trend in incidence of statin therapy. According to the regression analyses, the need-standardized statin incidence increased in men aged 40–64 by 17%, IRR 1.17 (95% CI: 1.14-1.19) with each increase in income quintile. In women the proportion was 23%, IRR 1.23 (1.16-1.29). An analogous pattern was seen applying education as SEP indicator and among subjects aged 65–84.
Conclusion
The high-risk strategy to prevent CVD by initiating statin therapy seems to be inequitable, reaching primarily high-risk subjects in lower risk SEP-groups.
doi:10.1186/1471-2458-12-610
PMCID: PMC3444315  PMID: 22863326
Statins to prevent cardiovascular disease; The high-risk strategy; Socioeconomic gradient; Horizontal equity
13.  Effect of statin treatment on short term mortality after pneumonia episode: cohort study 
Objective To determine whether statins protect against all cause mortality after a diagnosis of pneumonia.
Design Cohort study using propensity score based method to control for differences between people prescribed and not prescribed statins.
Setting United Kingdom Health Improvement Network database, which contains electronic primary care medical records of more than six million patients.
Participants Every patient starting a statin between 1995 and 2006 (129 288) matched with up to five non-statin users (n=600 241); 9073 patients had a recorded diagnosis of pneumonia, of whom 1398 were using a statin.
Main outcome measure All cause mortality within six months of diagnosis of pneumonia.
Results Among users and non-users of statins with comparable propensity scores, 95/942 users and 686/3615 non-users died on the day that pneumonia was diagnosed. In the following six month period, 109/847 statin users died compared with 578/2927 non-users, giving an adjusted hazard ratio of 0.67 (0.49 to 0.91). If these observed benefits translated into clinical practice, 15 patients would need to be treated with a statin for six months after pneumonia to prevent one death.
Conclusions Compared with people who were not taking statins, the risk of dying in the six month period after pneumonia was substantially lower among people who were already established on long term statin treatment when the pneumonia occurred. Whether some or all of this protective effect would be obtained if statin treatment begins when a patient first develops pneumonia is not known. However, given that statins are cheap, safe, and well tolerated, a clinical trial in which people with pneumonia are randomised to a short period of statin treatment is warranted.
doi:10.1136/bmj.d1642
PMCID: PMC3071610  PMID: 21471172
14.  Statins Impair Antitumor Effects of Rituximab by Inducing Conformational Changes of CD20 
PLoS Medicine  2008;5(3):e64.
Background
Rituximab is used in the treatment of CD20+ B cell lymphomas and other B cell lymphoproliferative disorders. Its clinical efficacy might be further improved by combinations with other drugs such as statins that inhibit cholesterol synthesis and show promising antilymphoma effects. The objective of this study was to evaluate the influence of statins on rituximab-induced killing of B cell lymphomas.
Methods and Findings
Complement-dependent cytotoxicity (CDC) was assessed by MTT and Alamar blue assays as well as trypan blue staining, and antibody-dependent cellular cytotoxicity (ADCC) was assessed by a 51Cr release assay. Statins were found to significantly decrease rituximab-mediated CDC and ADCC of B cell lymphoma cells. Incubation of B cell lymphoma cells with statins decreased CD20 immunostaining in flow cytometry studies but did not affect total cellular levels of CD20 as measured with RT-PCR and Western blotting. Similar effects are exerted by other cholesterol-depleting agents (methyl-β-cyclodextrin and berberine), but not filipin III, indicating that the presence of plasma membrane cholesterol and not lipid rafts is required for rituximab-mediated CDC. Immunofluorescence microscopy using double staining with monoclonal antibodies (mAbs) directed against a conformational epitope and a linear cytoplasmic epitope revealed that CD20 is present in the plasma membrane in comparable amounts in control and statin-treated cells. Atomic force microscopy and limited proteolysis indicated that statins, through cholesterol depletion, induce conformational changes in CD20 that result in impaired binding of anti-CD20 mAb. An in vivo reduction of cholesterol induced by short-term treatment of five patients with hypercholesterolemia with atorvastatin resulted in reduced anti-CD20 binding to freshly isolated B cells.
Conclusions
Statins were shown to interfere with both detection of CD20 and antilymphoma activity of rituximab. These studies have significant clinical implications, as impaired binding of mAbs to conformational epitopes of CD20 elicited by statins could delay diagnosis, postpone effective treatment, or impair anti-lymphoma activity of rituximab.
Jakub Golab and colleagues found that statins significantly decrease rituximab-mediated complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity against B cell lymphoma cells.
Editors' Summary
Background.
Lymphomas are common cancers of the lymphatic system, the tissues and organs that produce and store the white blood cells (lymphocytes) that fight infections. In healthy people, the cells in the lymph nodes (collections of lymphocytes in the armpit, groin, and neck) and other lymphatic organs divide to form new cells only when the body needs them. Lymphomas form when a T or B lymphocyte starts to divide uncontrollably. The first sign of lymphoma is often a painless swelling in the armpit, groin, or neck caused by lymphocyte overgrowth in a lymph node. Eventually, the abnormal (malignant) lymphocytes, which provide no protection against infectious diseases, spread throughout the body. Treatments for lymphoma include chemotherapy (drugs that kill rapidly dividing cells) and radiotherapy. In addition, a drug called rituximab was recently developed for the treatment of some types of B cell lymphoma. Rituximab is a monoclonal antibody, a laboratory-produced protein. It binds to a protein called CD20 that is present on the surface of both normal and malignant B lymphocytes and induces cell killing through processes called “complement-dependent cytotoxity” (CDC) and “antibody-dependent cellular cytotoxity” (ADCC).
Why Was This Study Done?
Although rituximab lengthens the lives of patients with some types of B cell lymphoma, it is not a cure—the lymphoma usually recurs. Researchers are trying to increase the effectiveness of rituximab by combining it with other anticancer agents. One group of drugs that might be combined with rituximab is the “statins,” drugs that reduce the risk of heart disease by lowering the level of cholesterol (a type of fat) in the blood. In laboratory experiments, statins kill some cancer cells, in part by altering the fat composition of their outer (plasma) membrane. In addition, some population-based studies suggest that statin treatment might slightly decrease the risk of developing some kinds of cancer, including lymphoma. Statins are already undergoing clinical evaluation in combination with chemotherapy for the treatment of lymphoma, but in this study, the researchers investigate the influence of statins on rituximab-induced killing of B cell lymphomas.
What Did the Researchers Do and Find?
When the researchers tested the ability of rituximab and statin combinations to kill B cell lymphoma cells growing in dishes, they found that statins decreased rituximab-dependent CDC and ADCC of these cells. Statin treatment, they report, did not alter the total amount of CD20 made by the lymphoma cells or the amount of CD20 in their plasma membranes, but it did reduce the binding of another anti-CDC20 monoclonal antibody to the cells. Because both this antibody and rituximab bind to a specific three-dimensional structure in CD20 (a “conformational epitope”), the researchers hypothesized that statins might alter rituximab-induced killing by affecting the shape of the CD20 molecule on the lymphoma cell surface. To test this idea, they used two techniques—atomic force microscopy and limited proteolysis. The data obtained using both approaches confirmed that statins induce shape changes in CD20. Finally, the researchers took B cells from five patients who had taken statins for a short time and showed that this treatment had reduced the amount of anti-CD20 monoclonal antibody able to bind to these cells.
What Do These Findings Mean?
These findings indicate that statins change the shape of the CD20 molecules on the surface of normal and malignant B lymphocytes, probably by changing the amount of cholesterol in the cell membrane. This effect of statins has several clinical implications, which means that cancer specialists should check whether patients with known or suspected B cell lymphoma are taking statins to treat high cholesterol. First, the impaired binding of monoclonal antibodies to conformational epitopes of CD20 in patients being treated with statins might delay the diagnosis of B cell lymphomas (CD20 binding to lymphocytes is used during the diagnosis of lymphomas). Second, some patients with B cell lymphoma may receive an incorrect diagnosis and may not be offered rituximab. Finally, because statins impair the anti-lymphoma activity of rituximab, a possibility that needs to be investigated in clinical studies, cancer specialists should check that patients with B cell lymphoma are not taking statins before prescribing rituximab.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050064.
The MedlinePlus has an encyclopedia page on lymphoma and a list of links to other sources of information on lymphoma (in English and Spanish)
The US National Cancer Institute provides information about lymphoma and about statins and cancer prevention (in English and Spanish)
The UK charity Cancerbackup provides information for patients and caregivers on different types of B-cell lymphoma and on rituximab
The US Leukemia and Lymphoma Society also provides information for patients and caregivers about lymphoma
doi:10.1371/journal.pmed.0050064
PMCID: PMC2270297  PMID: 18366248
15.  Evaluating an implementation strategy in cardiovascular prevention to improve prescribing of statins in Germany: an intention to treat analysis 
BMC Public Health  2013;13:623.
Background
The prescription of statins is an evidence-based treatment to reduce the risk of cardiovascular events in patients with elevated cardiovascular risk or with a cardiovascular disorder (CVD). In spite of this, many of these patients do not receive statins.
Methods
We evaluated the impact of a brief educational intervention in cardiovascular prevention in primary care physicians’ prescribing behaviour regarding statins beyond their participation in a randomised controlled trial (RCT). For this, prescribing data of all patients > 35 years who were counselled before and after the study period were analysed (each n > 75000). Outcome measure was prescription of Hydroxymethylglutaryl-CoA Reductase Inhibitors (statins) corresponding to patients’ overall risk for CVD. Appropriateness of prescribing was examined according to different risk groups based on the Anatomical Therapeutic Chemical Classification System (ATC codes).
Results
There was no consistent association between group allocation and statin prescription controlling for risk status in each risk group before and after study participation. However, we found a change to more significant drug configurations predicting the prescription of statins in the intervention group, which can be regarded as a small intervention effect.
Conclusion
Our results suggest that an active implementation of a brief evidence-based educational intervention does not lead to prescription modifications in everyday practice. Physician’s prescribing behaviour is affected by an established health care system, which is not easy to change.
Trial registration
ISRCTN71348772
doi:10.1186/1471-2458-13-623
PMCID: PMC3716622  PMID: 23819600
Evaluation studies; Intention to treat analysis; Cardiovascular diseases; Drug prescriptions; Hydroxymethylglutaryl-CoA Reductase Inhibitors
16.  The Effect of Alternative Summary Statistics for Communicating Risk Reduction on Decisions about Taking Statins: A Randomized Trial 
PLoS Medicine  2009;6(8):e1000134.
Carling and colleagues carry out a trial evaluating different methods of communicating information to people regarding the risks and benefits of taking statins. They suggest that natural frequencies are likely to be the most appropriate summary statistic for presenting the effects of treatment.
Background
While different ways of presenting treatment effects can affect health care decisions, little is known about which presentations best help people make decisions consistent with their own values. We compared six summary statistics for communicating coronary heart disease (CHD) risk reduction with statins: relative risk reduction and five absolute summary measures—absolute risk reduction, number needed to treat, event rates, tablets needed to take, and natural frequencies.
Methods and Findings
We conducted a randomized trial to determine which presentation resulted in choices most consistent with participants' values. We recruited adult volunteers who participated through an interactive Web site. Participants rated the relative importance of outcomes using visual analogue scales (VAS). We then randomized participants to one of the six summary statistics and asked them to choose whether to take statins based on this information. We calculated a relative importance score (RIS) by subtracting the VAS scores for the downsides of taking statins from the VAS score for CHD. We used logistic regression to determine the association between participants' RIS and their choice. 2,978 participants completed the study. Relative risk reduction resulted in a 21% higher probability of choosing to take statins over all values of RIS compared to the absolute summary statistics. This corresponds to a number needed to treat (NNT) of 5; i.e., for every five participants shown the relative risk reduction one additional participant chose to take statins, compared to the other summary statistics. There were no significant differences among the absolute summary statistics in the association between RIS and participants' decisions whether to take statins. Natural frequencies were best understood (86% reported they understood them well or very well), and participants were most satisfied with this information.
Conclusions
Presenting the benefits of taking statins as a relative risk reduction increases the likelihood of people accepting treatment compared to presenting absolute summary statistics, independent of the relative importance they attach to the consequences. Natural frequencies may be the most suitable summary statistic for presenting treatment effects, based on self-reported preference, understanding of and satisfaction with the information, and confidence in the decision.
Clinical Trials Registration
ISRCTN85194921
Please see later in the article for the Editors' Summary
Editors' Summary
Background
People often have to make decisions about their health care. Ideally, all the health care decisions that a person makes should be those best suited to his or her personal circumstances and expectations. Take, for example, someone with a high amount of cholesterol (a type of fat) in his or her blood. Because this condition increases the chances of developing potentially fatal coronary heart disease (CHD), such a person will often be advised by his or her doctor to take statins to reduce blood cholesterol levels. However, the person needs to consider both the benefits and downsides of this course of action. Can he or she afford to pay for statins, if their health care system requires him or her to? Does the person want to take a pill every day that might cause some side effects? That is, the person has to consider his or her “values”—the relative desirability of all the possible outcomes of taking statins—before deciding whether to follow his or her doctor's advice.
Why Was This Study Done?
It is well known that how information is presented to patients about treatment options and their consequences affects the choices that they make. For example, patients who are told that a drug will halve their chances of developing a disease (a 50% relative risk reduction) are more likely to decide to take that drug than those who are told it will reduce their absolute (actual) risk of developing the disease from 4% to 2%. Less is known, however, about which presentations of treatment effects best help people to make decisions that are consistent with their own values. In 2002, therefore, a series of internet-based randomized trials (studies in which participants are randomly allocated to different “treatment” groups) called the Health Information Project: Presentation Online (HIPPO) was initiated. Here, the researchers describe HIPPO 2, a trial that investigates how alternative summary statistics for communicating the reduction of CHD risk with statins affect people's decisions to take statins.
What Did the Researchers Do and Find?
Nearly 3,000 adults in Norway and North America rated the relative importance to them of CHD risk reduction, the cost of statins, and the need to take a daily pill through an interactive Web site. The researchers used these data to calculate a “relative importance score” (RIS), an indicator of each participant's values. Each participant then decided whether or not to take statins after being shown one of six summary statistics about the effect of statins on CHD risk (relative risk reduction and five indicators of absolute risk reduction). The presentation of the effect of statins as a relative risk reduction resulted in more people deciding to take statins over the whole RIS range than any of the absolute summary statistics. For every five participants shown the relative risk reduction statistic, an extra participant chose to take statins compared to the other summary statistics. When asked to compare the six summary statistics, the statistic that most people preferred and understood best was the “natural frequency,” an absolute summary statistic that gave the number of people likely to develop CHD with and without statin treatment.
What Do These Findings Mean?
Although these findings may not be generalizable to other populations or to other medical decisions, they provide new insights into how the presentation of information can affect the choices people make about health care. Specifically, these findings indicate that the presentation of the reduced risk of getting CHD as a result of taking stains as a relative amount is more likely to persuade people to take statins than several absolute summary statistics. They also suggest that the persuasive effect of the relative risk reduction summary statistic is not affected by the relative importance attached to the consequences of taking statins by individuals. That is, people shown the relative risk reduction statistic may be more likely to start statins to reduce their CHD risk (or a drug that reduces the risk of developing another disease) whatever their personal values than people shown absolute summary statistics. Finally, the findings on participant preferences suggest that natural frequencies may be the best summary statistic to include in tools designed to help people make decisions about their healthcare.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000134.
A PLoS Medicine Editorial discusses this trial and the results of another HIPPO trial that are presented in a separate PLoS Medicine Research Article by Carling and colleagues; details of a pilot HIPPO trial are also available
The Foundation for Informed Medical Decision Making (a US-based non-profit organization) provides information on many aspects of medical decision making
The Dartmouth-Hitchcock Medical Center provides information to help people make health care decisions through its Center for Shared Decision Making
The Ottawa Hospital Research Institute provides also information on patient decision aids, including an inventory of decision aids available on the Web (in English and French)
MedlinePlus provides links to information and advice about statins and about coronary heart disease (in English and Spanish)
doi:10.1371/journal.pmed.1000134
PMCID: PMC2724738  PMID: 19707575
17.  Efficacy of Short-Term High-Dose Statin in Preventing Contrast-Induced Nephropathy: A Meta-Analysis of Seven Randomized Controlled Trials 
PLoS ONE  2012;7(4):e34450.
Background
A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of shor-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy.
Methods
We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2–5 days after contrast administration and need for dialysis.
Results
Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR = 0.51, 95% CI 0.34–0.76, p = 0.001; I2 = 0%). The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05–2.10, p = 0.24; I2 = 0%). The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD −0.64, 95% CI: −1.57 to 0.29, P = 0.18, I2 = 97%).
Conclusions
Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention.
doi:10.1371/journal.pone.0034450
PMCID: PMC3325242  PMID: 22511942
18.  Statin Prescribing Patterns in a Cohort of Cancer Patients with Poor Prognosis 
Journal of Palliative Medicine  2013;16(4):412-418.
Abstract
Background
There are no evidence-based recommendations for statin continuation or discontinuation near the end of life. However, some expert opinion recommends continuing statins prescribed for secondary versus primary prevention of cardiovascular disease.
Objectives
Our aim was to explore statin prescribing patterns in a longitudinal cohort of individuals with life-limiting illness, and to evaluate differences in these patterns based on secondary versus primary prevention of cardiovascular disease.
Design and setting
This study was a retrospective cohort analysis of 539 persons in an integrated, not-for-profit health maintenance organization (HMO) setting who were receiving statins at diagnosis of a cancer with 0% to 25% predicted 5-year survival. Of the cohort patients, 343 were taking statins for secondary prevention and 196 for primary prevention of cardiovascular disease. Measurements included number and timing of statin refills between diagnosis and date of death, disenrollment, or the end of the observation period.
Results
Four hundred and ninety-six cohort members died within the observation period. Fifty-eight percent of the secondary prevention and 62% of the primary prevention group had at least one statin refill after diagnosis. There were no significant differences between groups for number of days between diagnosis and last refill, or between last refill and death. Two deaths were attributable to cardiovascular causes in each group.
Conclusions
Our retrospective cohort analysis of persons with incident poor-prognosis cancer describes diminished, but persistent statin refills after diagnosis. Neither timing of statin discontinuation nor cardiovascular mortality differed by prescribing indication. There may be an opportunity to reevaluate medication burden in persons taking statins for primary prevention, and it is unclear whether continuing statins prescribed for secondary prevention affects cardiovascular outcomes.
doi:10.1089/jpm.2012.0158
PMCID: PMC3612279  PMID: 23305190
19.  National Trends in Statin Use by Coronary Heart Disease Risk Category 
PLoS Medicine  2005;2(5):e123.
Background
Only limited research tracks United States trends in the use of statins recorded during outpatient visits, particularly use by patients at moderate to high cardiovascular risk.
Methods and Findings
Data collected between 1992 and 2002 in two federally administered surveys provided national estimates of statin use among ambulatory patients, stratified by coronary heart disease risk based on risk factor counting and clinical diagnoses. Statin use grew from 47% of all lipid-lowering medications in 1992 to 87% in 2002, with atorvastatin being the leading medication in 2002. Statin use by patients with hyperlipidemia, as recorded by the number of patient visits, increased significantly from 9% of patient visits in 1992 to 49% in 2000 but then declined to 36% in 2002. Absolute increases in the rate of statin use were greatest for high-risk patients, from 4% of patient visits in 1992 to 19% in 2002. Use among moderate-risk patients increased from 2% of patient visits in 1992 to 14% in 1999 but showed no continued growth subsequently. In 2002, 1 y after the release of the Adult Treatment Panel III recommendations, treatment gaps in statin use were detected for more than 50% of outpatient visits by moderate- and high-risk patients with reported hyperlipidemia. Lower statin use was independently associated with younger patient age, female gender, African American race (versus non-Hispanic white), and non-cardiologist care.
Conclusion
Despite notable improvements in the past decade, clinical practice fails to institute recommended statin therapy during many ambulatory visits of patients at moderate-to-high cardiovascular risk. Innovative approaches are needed to promote appropriate, more aggressive statin use for eligible patients.
The prescribing of statins shows great variation among different types of patients, with many who would benefit receiving neither lifestyle counseling nor appropriate drugs.
doi:10.1371/journal.pmed.0020123
PMCID: PMC1140942  PMID: 15916463
20.  Use of the Joint British Society cardiovascular risk calculator before initiating statins for primary prevention in hospital medicine: experience from a large university teaching hospital 
Introduction:
Statin therapy is a well established treatment for hyperlipidemia. However, little is known about prescribing of statins for primary prevention in the real world, and even less about what happens to patients requiring primary prevention who are seen in a secondary care setting. The purpose of this research was to investigate the appropriateness of statin prescriptions by using the Joint British Society cardiovascular disease (JBS CVD) risk score for primary prevention in a large secondary care center.
Methods:
We retrospectively analyzed 500 consecutive patients in whom a statin prescription was initiated over a four-month period. We excluded patients who met secondary prevention criteria. We used the JBS CVD risk prediction chart to calculate 10-year composite risk. We also studied which statins were prescribed and their starting doses.
Results:
Of 500 patients consecutively started on statins in secondary care, 51 patients (10.2%) were treated for primary prevention. Of these, seven (14%) patients had a 10-year composite cardiovascular event risk of more than 20% (high-risk category), and were hence receiving appropriate therapy. Three main statins were prescribed for primary prevention, ie, atorvastatin (22 patients, 43%), simvastatin (25 patients, 49%), and pravastatin (four patients, 8%). The statins prescribed were initiated mainly at the 40 mg dose.
Conclusions:
Statin prescribing in secondary care for primary prevention is limited to about 10% of initiations. There is some overprescribing, because 86% of these patients did not require statins when risk-stratified appropriately. The majority of the prescriptions were for simvastatin 40 mg and atorvastatin 40 mg.
doi:10.2147/IJGM.S14589
PMCID: PMC3008291  PMID: 21189835
statins; primary prevention; hypercholesterolemia; cardiovascular disease; retrospective
21.  Atherosclerosis, cholesterol, nutrition, and statins – a critical review 
Atherosclerosis, which causes approximately half of all deaths of adults over age 60 in industrialized nations, is a pandemic among inappropriately nourished and/or physically hypoactive children, adolescents, and adults world wide. Although nowadays statins are widely prescribed to middle age and elderly adults with high blood lipid levels as pharmacological prevention for the late complications of atherosclerosis, from a critical point of view statins seem not to solve the problem, especially when compared with certain natural ingredients of our nutrition like micronutrients as alternative strategy. Statin ingestion is associated with lowering of serum cholesterol and low-density lipoprotein concentrations; some prospective studies have shown statistical associations with subsequent modest reduction of mortality from cardiovascular disease. However, specific biochemical pathways and pharmacological roles of statins in prevention of atherosclerosis, if any, are unknown. Moreover, there have been no systematic cost-benefit analyses of life-style prophylaxis versus statin prophylaxis versus combined life-style plus statin prophylaxis versus neither life-style nor statin prophylaxis for clinically significant complications of cardiovascular diseases in the elderly. Further, in the trials of effectiveness statins were not compared with management of nutrition, which is the most appropriate alternative intervention. Such studies seem to be important, as the ever increasing world population, especially in developing countries, now demand expensive statins, which may be unaffordable for mitigating the pandemic. Studies of this kind are necessary to identify more precisely those patients for whom cardiovascular benefits will outweigh the risks and costs of the statin treatment in comparison with nutritional interventions.
Against the background of the current pathogenetic concept of atherogenesis some of its possible risk factors, particularly the roles of cholesterol and homocysteine, and the effects of statins versus nutritional (micronutrients) interventions in prevention and treatment of the disease are discussed. The prevailing opinion that serum cholesterol as a mediator of the disease is increased by eating saturated fats and decreased by eating polyunsaturated fats is being challenged. Evidently, the beneficial effects of statins in atherosclerosis are not mainly due to its cholesterol lowering effect, rather than to its “pleiotropic effects”. Other pathogenetic factors in atherosclerosis are involved, like inflammatory and immunologic processes, that can be modulated by statins as well as by other drugs or by the Mediterranean-style nutrition and by micronutrients (folate, B-vitamins).
PMCID: PMC2703237  PMID: 19675712
atherosclerosis; nutrition; micronutrients; statins; homocysteine; lipid-hypothesis; cholesterol; Mediterranean-style nutrition; B-vitamins; folate; Atorvastatin; Simvastatin
22.  Cholesterol treatment with statins: Who is left out and who makes it to goal? 
Background
Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education) are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C) therapy goals are not known. We examined socio-demographic factors associated with a) eligibility for statin therapy among those not on statins, and b) achievement of statin therapy goals.
Methods
Adults (21-79 years) participating in the United States (US) National Health and Nutrition Examination Surveys, 1999-2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III) on Treatment of High Cholesterol guidelines.
Results
Among 6,043 participants not taking statins, 10.4% were eligible. Adjusted predictors of statin eligibility among statin non-users were being older, male, poorer, and less educated. Hispanics were less likely to be eligible but not using statins, an effect that became non-significant with adjustment for language usually spoken at home. Among 537 persons taking statins, 81% were at LDL-C goal. Adjusted predictors of goal failure among statin users were being male and poorer. These risks were not attenuated by adjustment for healthcare access or utilization.
Conclusion
Among person's not taking statins, the socio-economically disadvantaged are more likely to be eligible and among those on statins, the socio-economically disadvantaged are less likely to achieve statin treatment goals. Further study is needed to identify specific amenable patient and/or physician factors that contribute to these disparities.
doi:10.1186/1472-6963-10-68
PMCID: PMC2846927  PMID: 20236527
23.  Optimizing secondary prevention: Statin prescribing across East and West London in accordance with NICE guidelines 
JRSM Short Reports  2011;2(7):63.
Objectives
Statins are a well-known primary and secondary prevention drug for cardiovascular disease and NICE guidelines have been issued to identify key indicators for their use. An audit looking into statin prescribing for medical inpatients was carried out in two geographically distinct London hospitals.
Design
A prospective inpatient audit of medical prescription charts was performed. Blood results were reviewed for the inpatients during their admission to identify any contraindications for statin usage (rhabdomyolysis). The medical notes were also reviewed for patient refusal of statin therapy.
Setting
The study was carried out at two distinct hospitals in London. Whipps Cross University Hospital (WCUH) and Chelsea & Westminster Hospital (CWH) are located in East London and West London, respectively. Acute medical, surgical, obstetrics and gynaecology, paediatric and palliative wards were excluded.
Participants
A total of 309 inpatient medical notes and prescription chart data were collected from WCUH (n = 211) and CWH (n = 98).
Main outcome measures
High percentage of hospitalized patients are not prescribed statins despite clear clinical indications for their use. Regardless of geographical and socioeconomic factors between hospitals, statin prescribing remains suboptimal.
Results
The patient demographics in both hospitals were very similar; the mean age at WCUH was 78 ± 15 1SD while at CWH the mean age was 74 ± 15 1SD. The results showed that approximately one-third of patients (30% at WCUH and 33% at CWH) had at least one indication for statin therapy according to NICE guidelines and yet they were not prescribed a statin. Ten percent of patients at WCUH and 13% of patients at CWH had ischaemic heart disease (IHD) and yet were not prescribed statins.
Conclusion
Statin prescription is often overlooked in secondary care with patients being discharged without the appropriate assessment (NICE guidelines), which subsequently means repeat prescriptions are not provided by the GP. This study is the first to show that this problem is not due to resources or geography, but is inherent within the NHS system. Consequently, a revised prescription chart checking system has been suggested for pharmacists and junior doctors.
doi:10.1258/shorts.2011.011027
PMCID: PMC3147237  PMID: 21847445
24.  Statin therapy as prevention against development of acute respiratory distress syndrome: An observational study* 
Critical care medicine  2012;40(5):1470-1477.
Objectives
The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (“statins”) have anti-inflammatory properties and are associated with improved outcomes in critically ill patients. We investigated whether previous statin therapy affects outcomes in patients at risk for acute respiratory distress syndrome.
Design
Patients were followed-up for the primary outcome of acute respiratory distress syndrome and secondary outcomes of intensive care unit and 60-day mortality, organ dysfunction, and ventilator-free days in a secondary analysis of a prospective cohort study. Receipt of statin therapy was recorded. Propensity score matching was used to adjust for confounding by indication.
Setting
Intensive care units at a tertiary care academic medical center.
Patients
Critically ill patients (2,743) with acute respiratory distress syndrome risk factors.
Interventions
None.
Measurements and Main Results
Acute respiratory distress syndrome developed in 738 (26%) patients; 413 patients (15%) received a statin within 24 hrs of intensive care unit admission. Those who had received a statin within 24 hrs had a lower rate of development of acute respiratory distress syndrome (odds ratio 0.56; 95% confidence interval 0.43–0.73; p < .0001). After multivariate adjustment for potential confounders, this association remained significant (odds ratio 0.69; 95% confidence interval 0.51–0.92; p = .01). However, after propensity score matching, the association was not statistically significant (odds ratio 0.79; 95% confidence interval 0.57–1.10; p = .16). Statin use was not associated with reduced acute respiratory distress syndrome mortality, organ dysfunction, or ventilator-free days. Results of the study were presented in accordance with STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.
Conclusions
Statin therapy at the time of intensive care unit admission was not associated with a lower rate of development of acute respiratory distress syndrome after matching for patient propensity to receive statins. Statin therapy was not associated with improvements in acute respiratory distress syndrome mortality, organ failure, or days free from mechanical ventilation.
doi:10.1097/CCM.0b013e3182416d7a
PMCID: PMC3939937  PMID: 22430234
ALI/ARDS; critical illness; statin
25.  Association between statin therapy and outcomes in critically ill patients: a nested cohort study 
Background
The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.
Methods
This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.
Results
Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.
Conclusion
Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.
doi:10.1186/1472-6904-11-12
PMCID: PMC3199769  PMID: 21819615

Results 1-25 (1187859)