PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (45)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
1.  Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes 
Background
Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes.
Methods
In this double-blind, controlled, cross-over trial 50 patients (without clinical signs of microvascular alterations) with type-2 diabetes (mean duration of 4 years) were randomized to receive placebo or 5 mg saxagliptin for 6 weeks. Retinal arteriolar structure and retinal capillary flow (RCF) at baseline and during flicker-light exposure was assessed by scanning laser Doppler flowmetry. Central hemodynamics were assessed by pulse wave analysis.
Results
Postprandial blood glucose (9.27 ± 0.4 versus 10.1 ± 0.4 mmol/L; p = 0.001) and HbA1c (6.84 ± 0.15 (51 ± 1.6) versus 7.10 ± 0.17% (54 ± 1.9 mmol/mol); p < 0.001) were significantly reduced with saxagliptin treatment compared to placebo. RCF was significantly reduced after treatment with saxagliptin (288 ± 13.2 versus 314 ± 14.1 AU; p = 0.033). This was most pronounced in a subgroup of patients (n = 32) with a fall in postprandial blood glucose (280 ± 12.1 versus 314 ± 16.6 AU; p = 0.011). No significant changes in RCF were seen during flicker-light exposure between placebo and saxagliptin, but the vasodilatory capacity increased two-fold with saxagliptin treatment. Central augmentation pressure tended to be lower after treatment with saxagliptin (p = 0.094), and central systolic blood pressure was significantly reduced (119 ± 2.3 versus 124 ± 2.3 mmHg; p = 0.038).
Conclusions
Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes.
Trial registration
The study was registered at (ID: NCT01319357).
doi:10.1186/1475-2840-13-19
PMCID: PMC3897922  PMID: 24423149
Saxagliptin; DPP-4 inhibitor; Type-2 diabetes; Retinal blood flow; Central hemodynamics
2.  Results of the Dyslipidemia International Study (DYSIS)-Middle East: Clinical Perspective on the Prevalence and Characteristics of Lipid Abnormalities in the Setting of Chronic Statin Treatment 
PLoS ONE  2014;9(1):e84350.
Background
Therapeutic intervention with low-density lipoprotein cholesterol-lowering agents known as statins has been demonstrated to reduce cardiovascular risk. However, many patients on statin treatment have persistent dyslipidemia and remain at a high risk of cardiovascular disease. Therefore, the objective of this study was to assess the frequency of lipid abnormalities in patients receiving chronic statin treatment.
Methods
As part of an international, cross-sectional, observational study, DYSIS-Middle East enrolled 2,182 patients in the United Arab Emirates (UAE), Saudi Arabia, Lebanon and Jordan. All patients were over 45 years of age and had been on statin treatment for at least three months. Data on demographics, lipid parameters and cardiovascular risk profile were recorded. Cardiovascular risk was defined according the guidelines of the European Society of Cardiology.
Results
The majority of patients (82.6%) were classified as being at very high risk of cardiovascular events, and 61.8% of all patients did not attain LDL-C target levels. Low high-density lipoprotein cholesterol levels and elevated triglyceride levels were noted in 55.5% and 48.5% of patients, respectively. Multivariate logistical regression modeling indicated that factors independently associated with LDL-C levels not being at goal were lifestyle choices, diabetes mellitus, ischemic heart disease, and blood pressure ≥ 140/90 mmHg.
Conclusions
Almost two-thirds of statin-treated patients in the United Arab Emirates, Saudi Arabia, Lebanon and Jordan had inadequately controlled lipid levels. More comprehensive surveillance, awareness and treatment regimens, as well as modification of lifestyle choices, is necessary to halt the rise in cardiovascular disease-related mortality.
doi:10.1371/journal.pone.0084350
PMCID: PMC3882235  PMID: 24400085
3.  Efficacy and safety of insulin glargine added to a fixed-dose combination of metformin and a dipeptidyl peptidase-4 inhibitor: results of the GOLD observational study 
Background
For patients with type 2 diabetes who are uncontrolled on a combination of two oral antidiabetic agents, addition of the long-acting basal insulin glargine is a well established treatment option. However, data on the efficacy and safety of a combination of metformin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin glargine are limited in real-world settings. Therefore, the aim of this study was to analyze blood glucose control, rates of hypoglycemia and body weight in a large cohort of patients with type 2 diabetes treated with this combination therapy in real practice.
Methods
This noninterventional, multicenter, prospective, observational trial with a follow-up of 20 weeks enrolled insulin-naïve patients who had been on a stable fixed dose of metformin and a DPP-4 inhibitor for at least 3 months, and had a glycosylated hemoglobin (HbA1c) between 7.5% and 10%. Patients were selected at the investigators’ discretion for initiation of insulin glargine at baseline. A total of 1,483 patients were included, of whom 1,262 were considered to be the efficacy set. Primary efficacy parameters were HbA1c and fasting plasma glucose. Secondary outcome measures included achievement of glycemic targets, body weight, rates of hypoglycemia, and other safety parameters, as well as resource consumption.
Results
Upon initiation of insulin glargine, mean HbA1c decreased from 8.51% to 7.36% (−1.15%±0.91%; 95% confidence interval [CI] −1.20 to −1.10). An HbA1c level <6.5% was achieved in 8.2% of patients and a level <7.0% in 31.5%. Mean fasting plasma glucose decreased from 174±47 mg/dL to 127±31 mg/dL (−47.3±44.1 mg/dL; 95% CI −49.8 to −44.8). In 11.9% of patients, a fasting plasma glucose level <100 mg/dL was achieved. Bodyweight decreased on average by 0.98±3.90 kg (95% CI 1.19–0.76). Hypoglycemia (blood glucose ≤70 mg/dL) was observed in 29 patients (2.30%), of whom six (0.48%) had nocturnal hypoglycemia and four (0.32%) had documented severe events (blood glucose <56 mg/dL).
Conclusion
The results of this observational study show that insulin glargine, when added to a fixed-dose combination of metformin and a DPP-4 inhibitor, resulted in a significant and clinically relevant improvement of glycemic control. Importantly, this intervention did not interfere with the action of the DPP-4 inhibitors, resulting in neutral effects on weight and low rates of hypoglycemia. We conclude that this treatment intensification approach may be useful, efficient, and safe in daily clinical practice for patients with type 2 diabetes.
doi:10.2147/VHRM.S54362
PMCID: PMC3833837  PMID: 24259985
diabetes; dipeptidyl dipeptidase-4 inhibitors; metformin; insulin glargine
4.  Prevalence of dyslipidaemia in statin-treated patients in South Africa: results of the DYSlipidaemia International Study (DYSIS) 
Cardiovascular Journal of Africa  2013;24(8):330-338.
Introduction and objectives
Cardiovascular disease (CVD) is the leading cause of mortality worldwide and increased levels of low-density lipoprotein cholesterol (LDL-C) are an important modifiable risk factor. Statins lower LDL-C levels and have been shown to reduce CVD risk. Despite the widespread availability of statins, many patients do not reach the lipid targets recommended by guidelines. We evaluated lipid goal attainment in statin-treated patients in South Africa and analysed variables contributing to poor goal attainment as part of the DYSlipidaemia International Study (DYSIS).
Methods
This cross-sectional, observational study enrolled 1 029 consecutive South African patients consulting officebased physicians. Patients were at least 45 years old, had to be treated with a stable dose of statins for at least three months and had been fasting for 12 hours. We evaluated lipid goal attainment and examined variables associated with residual dyslipidaemia [abnormal levels of LDL-C, highdensity lipoprotein cholesterol (HDL-C) and/or triglycerides (TG)].
Results
We found that 50.3% of the patients overall did not achieve target LDL-C levels and 73.5% of patients were at very high cardiovascular risk. In addition, 33.7% had low levels of HDL-C, while 45.3% had elevated TG levels despite statin therapy. Asian and mixed-ancestry patients but not black (vs Caucasian ethnicity), as well as obese individuals in South Africa were more likely to still have dyslipidaemia involving all three lipid fractions.
Conclusions
We observed that many patients in South Africa experienced persistent dyslipidaemia despite statin treatment, supporting the concept that there is a need for more intensive statin therapy or the development of novel treatment strategies. Measures aimed at combating obesity and other lifestyle-related risk factors are also vital for effectively controlling dyslipidaemia and reducing the burden of CVD.
doi:10.5830/CVJA-2013-071
PMCID: PMC3821092  PMID: 24240385
cardiovascular disease (CVD); dyslipidaemia; lipid abnormalities; statins; low-density lipoprotein cholesterol (LDL-C)
5.  Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review 
Background
Hypoglycaemia has been associated with increased cardiovascular (CV) risk and mortality in a number of recent multicentre trials, but the mechanistic links driving this association remain ill defined. This review aims to summarize the available data on how hypoglycaemia may affect CV risk in patients with diabetes.
Methods
This was a systematic review of available mechanistic and clinical studies on the relationship between hypoglycaemia and cardiovascular risk. Study outcomes were compiled from relevant articles, and factors contributing to hypoglycaemia-mediated CVD and its complications are discussed.
Results
Six recent comprehensive clinical trials have reinforced the critical importance of understanding the link between hypoglycaemia and the CV system. In addition, 88 studies have indicated that hypoglycaemia mechanistically contributes to CV risk by increasing thrombotic tendency, causing abnormal cardiac repolarization, inducing inflammation, and contributing to the development of atherosclerosis. These hypoglycaemia-associated risk factors are conducive to events such as unstable angina, non-fatal and fatal myocardial infarction, sudden death, and stroke in patients with diabetes.
Conclusions
Emerging data suggest that there is an impact of hypoglycaemia on CV function and mechanistic link is multifactorial. Further research will be needed to ascertain the full impact of hypoglycaemia on the CV system and its complications.
doi:10.1186/1475-2840-12-135
PMCID: PMC3849493  PMID: 24053606
Hypoglycaemia; Cardiovascular risk; Arrhythmia; Continuous glucose monitoring; Randomized controlled trials
6.  Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice 
Background
The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ) as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control.
Methods
In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs.
Results
The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19), and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001), but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients, blood pressure was normalized (<140/90 mmHg). No noteworthy differences in baseline characteristics or baseline blood pressure were found between patients with an activity level (sum of weekly energy costs) above or below the median of 9,460.6. A higher versus lower physical activity score had no impact on blood pressure reduction.
Conclusion
Our data confirm randomized trial data concerning safe and efficient blood pressure reduction using a fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent of physical activity level.
doi:10.2147/VHRM.S49118
PMCID: PMC3769201  PMID: 24039432
blood pressure; antihypertensive agents; administration; dosage; physical activity
7.  EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy – rationale and design of the EARLY hypertension registry 
Background
Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions.
Methods/Design
The “Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy” (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013.
Conclusions
The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice.
doi:10.1186/1471-2261-13-46
PMCID: PMC3706336  PMID: 23819631
Azilsartan; Ramipril; ACE-Inhibitors; Non-Interventional; Blood Pressure; Follow-up; Ambulatory Blood Pressure Measurement; Central Systolic Blood Pressure
8.  The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes 
Metformin is, if not contraindicated and if tolerated, usually preferred over other antidiabetic drugs for the first line treatment of type-2 diabetes. The particular decision on which antidiabetic agent to use is based on variables such as efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia, risk, and patient preferences. However, there is no guidance how to consider these in the selection of antidiabetic drug treatment. In this work, we aimed to summarize available evidence and tried to give pragmatic treatment recommendations from a clinical practice perspective.
There are clear contraindications for some drugs in those with impaired renal and liver function and precautions in those with heart failure for the use of metformin (NYHA III-IV) and glitazones. On the other hand, GLP-1 analogs, DPP-4 inhibitors and acarbose are generally less critical and can be used in the majority of patients. We identified the following gaps with respect to the selection of antidiabetic drug treatment in patients with co-morbid disease conditions: 1) Guidelines fail to give advice on the use of specific antidiabetic drugs in patients with co-morbidity. 2) The literature is deficient in studies documenting antidiabetic drug use in patients with severely impaired renal function, diabetic retinopathy, cerebrovascular disease and systolic heart failure. 3) Further there are no specific data on patients with multiple of these co-morbid disease conditions. We postulate that differential use of antidiabetic drugs in patients with co-morbid disease constellations will help to reduce treatment related complications and might improve prognosis.
doi:10.1186/1475-2840-12-62
PMCID: PMC3664601  PMID: 23574917
9.  Co-morbidity but not dysglycaemia reduces quality of life in patients with type-2 diabetes treated with oral mono- or dual combination therapy – an analysis of the DiaRegis registry 
Background
Type-2 diabetes mellitus has a major impact on health related quality of life (HRQoL). We aimed to identify patient and treatment related variables having a major impact.
Methods
DiaRegis is a prospective diabetes registry. The EQ-5D was used to describe differences in HRQoL at baseline. Odds ratios (OR) with 95% confidence intervals (CI) were determined from univariable regression analysis. For the identification of independent predictors of a low score on the EQ-5D, multivariable unconditional logistic regression analysis was performed.
Results
A total of 2,760 patients were available for the present analysis (46.7% female, median age 66.2 years). Patients had considerable co-morbidity (18.3% coronary artery disease, 10.6% heart failure, 5.9% PAD and 5.0% stroke/TIA). Baseline HbA1c was 7.4%, fasting- and postprandial plasma glucose 139 mg/dl and 183 mg/dl.
The median EQ-5D was 0.9 (interquartile range [IQR] 0.8–1.0). Independent predictors for a low EQ-5D were age > 66 years (OR 1.49; 95%CI 1.08–2.06), female gender (2.11; 1.55–2.86), hypertension (1.73; 1.03–2.93), peripheral neuropathy (1.62; 0.93–2.84) and clinically relevant depression (11.01; 3.97–30.50). There was no influence of dysglycaemia on the EQ-5D score.
Conclusion
The present study suggests, that co-morbidity but not average glycaemic control reduces health related quality of life in type 2 diabetes mellitus.
doi:10.1186/1475-2840-12-47
PMCID: PMC3606825  PMID: 23510200
10.  Achievement of recommended glucose and blood pressure targets in patients with type 2 diabetes and hypertension in clinical practice – study rationale and protocol of DIALOGUE 
Background
Patients with type 2 diabetes have 2–4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD.
Methods
DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1) individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE) and the rate of hospitalizations are the most important.
Conclusion
The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti-diabetic and anti-hypertensive drugs in clinical trials and their real world balance of effectiveness and safety.
doi:10.1186/1475-2840-11-148
PMCID: PMC3537604  PMID: 23216660
Type-2 diabetes; Hypertension; Efficacy; Effectiveness; Safety; Vildagliptin
11.  Incidence and predictors of hypoglycaemia in type 2 diabetes – an analysis of the prospective DiaRegis registry 
Background
Hypoglycaemia is a serious adverse effect of antidiabetic drug therapy. We aimed to determine incidence rates of hypoglycaemia in type-2 diabetic patients and identify predictors of hypoglycaemia when treatment is intensified.
Methods
DiaRegis is a prospective German registry that follows 3810 patients with type-2 diabetes referred for treatment intensification because of insufficient glycaemic control on one or two oral antidiabetic drugs.
Results
Out of a total of 3347 patients with data available for the present analysis 473 (14.1%) presented any severity hypoglycaemia over a follow-up of 12 months. 0.4% were hospitalized (mean of 1.3±0.6 episodes), 0.1% needed medical assistance (1.0±0.0), 0.8% needed any help (1.1±0.5) and 10.1% no help (3.4±3.7), and 8.0% had no specific symptoms (3.6±3.5). Patients with incident hypoglycaemia had longer diabetes duration, higher HbA1c and a more frequent smoking history; more had co-morbid disease conditions such as coronary artery disease, peripheral arterial disease, amputation, heart failure, peripheral neuropathy, diabetic retinopathy and clinically relevant depression at baseline. Multivariable adjusted positive predictors of incident hypoglycaemia over the follow-up were prior anamnestic hypoglycaemia, retinopathy, depression, insulin use and blood glucose self-measurement, but not sulfonylurea use as previously reported for anamnestic or recalled hypogylcaemia. On the contrary, glitazones, DPP-4 inhibitors and GLP-1 analogues were associated with a reduced risk of hypoglycaemia.
Conclusions
Hypoglycaemia is a frequent adverse effect in ambulatory patients when antidiabetic treatment is intensified. Particular attention is warranted in patients with prior episodes of hypoglycaemia, microvascular disease such as retinopathy and in patients receiving insulin. On the other hand glitazones, DPP-4 inhibitors and GLP-1 analogues are associated with a reduced risk.
doi:10.1186/1472-6823-12-23
PMCID: PMC3515411  PMID: 23075070
12.  Oral antidiabetic treatment in type-2 diabetes in the elderly: balancing the need for glucose control and the risk of hypoglycemia 
Background
We aimed at identifying variables predicting hypoglycemia in elderly type 2 diabetic patients and the relation to HbA1c values achieved.
Design
Prospective, observational registry in 3810 patients in primary care. Comparison of patients in different age tertiles: with an age < 60 (young, n=1,253), age 60 to < 70 (middle aged, n=1,184) to those ≥ 70 years (elderly, n=1,373). Odds Ratios (OR) with 95% confidence intervals (CI) were determined from univariable and multivariable regression analyses.
Results
Elderly patients had a later diabetes diagnosis, a longer diabetes duration, better glucose control and more frequent co-morbid disease conditions. Overall 10.7% of patients experienced any severity hypoglycemia within the last 12 months prior to inclusion. Higher rates of hypoglycemia were observed in the elderly than in the young after adjusting for differences in HbA1c, fasting and post-prandial blood glucose (OR 1.68; 95%CI 1.16-2.45). This was particularly true for hypoglycemic episodes without specific symptoms (OR 1.74; 95%CI 1.05-2.89). In a multivariate model stroke / transitory ischemic attack, the presence of heart failure, clinically relevant depression, sulfonylurea use and blood glucose self-measurement were associated with hypoglycemic events.
Conclusion
Elderly patients are at an increased risk of hypoglycemia even at comparable glycemic control. Therefore identified variables associated with hypoglycemia in the elderly such as heart failure, clinically relevant depression, the use of sulfonylurea help to optimize the balance between glucose control and low levels of hypoglycemia. Asymptomatic hypoglycemia should not be disregarded as irrelevant but considered as a sign of possible hypoglycemia associated autonomic failure.
doi:10.1186/1475-2840-11-122
PMCID: PMC3508810  PMID: 23039216
13.  Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation 
BMC Neurology  2012;12:102.
Background
Patients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU) is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study.
Methods
The INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation) registry is the first to provide large scale data on 1,167 patients with acute stroke (< 3 months) that survived the initial phase of high risk and were undergoing neurologic in-patient rehabilitation. MAU was determined by dipstick-testing and correlated to baseline clinical variables (stroke-origin, functional impairment, co-morbidity, ankle-brachial-index, intima-media-thickeness) as well as vascular events after one year of follow-up. Comparisons were made with the χ2 or Mann–Whitney-U Test. Relative risks (RR) with 95% confidence intervals (CI) were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR) using Cox proportional hazard regression.
Results
A substantial proportion of patients was MAU positive at baseline (33.1%). Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p < 0.0001), had a slightly higher body mass index (27.8 vs. 27.1 kg/m2; p = 0.03) and increased waist circumference (79.5 vs. 50.4% for women [p < 0.0001] and 46.8 vs. 43.2% for men [p = 0.04]) and twice as often had diabetes mellitus (41.8 vs. 20.1%; p < 0.0001). Patients with MAU had a similar NIH stroke scale score (median 3 vs. 3; p = 0.379) but had lower values on the Barthel Index (median 75 vs. 90; p < 0.001). They had higher rates of atrial fibrillation (RR 1.38; 95% CI 1.09-1.75), coronary artery disease (RR 1.54; 95% CI 1.18-2.00), heart failure (RR 1.70; 95% CI 1.10-2.60) symptomatic peripheral artery disease (RR 2.30; 95% CI 1.40-3.80) and atherosclerotic stroke etiology (53.7 vs. 35.4%; p < 0.0001). MAU was associated with an increased intima-media-thickness, decreased ankle-brachial-index and polyvascular disease (RR 1.56; 95%CI 1.31-1.99). The event rate after a median follow-up of 13 months was 6.7% for fatal or nonfatal stroke, 4.7% for death, and 10.9% for combined vascular events (stroke, MI, vascular death). The presence of MAU was predictive for vascular events during the following year (HR for total mortality 2.2; 95% CI 1.3-3.7; HR for cardiovascular events 2.3; 95% 1.2 - 4.4).
Conclusions
INSIGHT demonstrated a significant association between MAU and polyvascular disease and further supports previous findings that MAU predicts cardio-/cerebrovascular events in patients recovering from ischemic stroke. This biomarker may also be used in patients during neurologic in-patient rehabilitation, opening a window of opportunity for early intervention in this patient group at increased risk for recurrent events.
doi:10.1186/1471-2377-12-102
PMCID: PMC3517490  PMID: 23007013
14.  Diabetes prevalence and metabolic risk profile in an unselected population visiting pharmacies in Switzerland 
Background
Diabetes represents one of the major health challenges in Switzerland, and early diagnosis and treatment is mandatory to prevent or delay diabetes-related morbidity and mortality. For the purpose of identifying affected individuals, early screening in pharmacies is a valuable option. In this survey, we aimed to determine blood glucose and metabolic control in an unselected population of individuals visiting Swiss pharmacies.
Methods
The subjects responded to a short questionnaire and underwent a single capillary blood glucose test for screening purposes. They were classified as normal, indeterminate, impaired fasting glucose, and diabetes according to predefined blood glucose levels.
Results
A total of 3135 individuals (mean age 56 years) in 18 cantons were screened in November 2010; of these, 4.2% (95% confidence interval [CI] 3.5–4.9) had previously been diagnosed with diabetes. Diabetes was newly diagnosed in 1.9% (95% CI 1.5–2.4), and 11.5% (95% CI 10.4–12.6) had impaired fasting glucose. Subjects with impaired glucose control had an increased body mass index, a frequent family history of diabetes, hypertension, hypercholesterolemia, smoking, and a low level of physical activity. Prevalence of impaired glucose control was different between the French/Italian-speaking part of Switzerland (new diabetes 4.9%; impaired fasting glucose 12.7%) and the German-speaking part (new diabetes 1.9%; impaired fasting glucose 10.3%).
Conclusion
Our study shows a 6.1% prevalence of diabetes, of which about a third (1.9%) was previously undiagnosed, and 11.5% had impaired fasting glucose. Therefore, screening initiatives in pharmacies may be suitable for detecting people with undiagnosed diabetes.
doi:10.2147/VHRM.S35896
PMCID: PMC3459687  PMID: 23049259
diabetes; pharmacy; epidemiology; screening
15.  Improved survival of patients with coronary artery disease and low ejection fraction with ICD implantation versus conventional therapy in a real world survey 
BMC Research Notes  2012;5:382.
Background
Coronary artery disease (CAD) is associated with an increased risk for sudden cardiac death. Randomized controlled trials have shown that implantable cardioverter defibrillators (ICD) improve life expectancy unless they are implanted within the first days after an acute myocardial infarction and guidelines recommend their use. We aimed to validate that these results also apply to patients of a typical community hospital in Germany.
Methods
This was a retrospective analysis of patients undergoing coronary angiography in the Lippe-Detmold Hospital between 2003 and 2006. They had to have significant CAD and an ejection fraction (EF) ≤ 35% and no acute myocardial infarction within 28 days of implantation and no history of ventricular fibrillation.
Results
213 patients were included; 70 of which received an ICD. Patients with an ICD implantation were younger (64.8 ± 9.9 vs. 67.9 ± 9.8 years; p = 0.034), had single vessel CAD more frequently (22.9 vs. 11.2%; p = 0.025) and a lower EF (26.7 ± 6.3 vs. 29.1 ± 4.6%; p = 0.006). Hospital readmissions were comparable between the ICD and the control group (68.6 vs. 72.0%; p = 0.602). ICD therapy was associated with a considerable survival benefit compared to conventional therapy (HR 0.52; 95%CI 0.29-0.93; p = 0.027) in a Cox-Proportional Hazards Regression analysis.
Conclusions
Appreciating the potential limitations of retrospective studies, we found that ICD use was associated with improved survival in patients with significant CAD and an EF <= 35% typical for a large tertiary hospital.
doi:10.1186/1756-0500-5-382
PMCID: PMC3457837  PMID: 22840219
Implantable cardioverter defibrillator; Cohort study; Myocardial infarction
16.  A multi-center, prospective, open-label, 8-week study of certoparin for anticoagulation during maintenance hemodialysis – the membrane study 
BMC Nephrology  2012;13:50.
Background
Adequate anticoagulation is prerequisite for effective hemodialysis to prevent clotting in the extracorporeal circuit. We aimed providing first data on the efficacy and safety of the low-molecular-weight heparin certoparin in this setting.
Methods
Multicenter, open-label, 8-week trial. Patients received a single dose of 3,000 IU certoparin i.v. with additional titration steps of 600 IU and/or continuous infusion if necessary.
Results
120 patients were screened, 109 enrolled (median age 71; range 26–90 years) and 106 available for efficacy analyses. The percentage of unsatisfactory dialysis results at 8 weeks due to clotting or bleeding, was 1.9% (n = 2/106; 95% confidence interval [CI] 0.23–6.65%); no major bleeding. 1.9% had moderate/severe clotting in the lines/bubble catcher and 2.8% in the dialyser at week 8. 15.7 ± 14.3% of the dialysis filters’ visual surface area was showing redness. In subgroups of patients receiving median doses of 3000 ± 0, 3000 (2400–6000) and 4200 (3000–6600) IU, plasma aXa levels at baseline, 4 and 8 weeks were 0.24 [95%CI 0.21–0.27], 0.33 [0.27–0.40] and 0.38 [0.33–0.45] aXa IU/ml at 2 h. C48h was 0.01 [0.01–0.02] aXa IU at all visits. At baseline and 4 weeks AUC0-48h was 2.66 [2.19–3.24] and 3.66 [3.00–4.45] aXa IU*h/ml. In 3.0% of dialyses (n = 83/2724) prolonged fistula compression times were documented. Eight patients (7.34%) had at least one episode of minor bleeding. 4) 85.3% of patients had any adverse event, 9.2% were serious without suspected drug relation; and in 32 patients a drug-relation was suspected.
Conclusions
Certoparin appears effective and safe for anticoagulation in patients undergoing maintenance hemodialysis.
doi:10.1186/1471-2369-13-50
PMCID: PMC3508880  PMID: 22742742
17.  Comparison of 3,000 and 5,000 IU aXa/day certoparin in the prevention of deep-vein thrombosis after total hip replacement 
Thrombosis Journal  2012;10:10.
Background
The aim was to investigate, whether 5,000 IUaXa/day certoparin lowers the incidence of deep vein thrombosis (DVT) in patients undergoing elective hip replacement surgery vs. 3,000 IUaXa/day. Double-blind, multicenter, randomised trial in 500 patients. Primary endpoint: incidence of symptomatic or asymptomatic DVT (bilateral ascending venography).
Results
Mean age was 71 ± 10 years with a higher prevalence of previous DVT (8vs.4%) and pulmonary embolism (PE) (4vs.1%) in the high dose group. Mean duration of surgery was 82 ± 32 and 85 ± 36 min. DVT was detected in 28 (11.1%) of the low dose and 35 (14.1%) of the high dose group (p = n.s.). Combined distal-proximal DVT was observed in 5 (2%) and 4 (1.6%) patients respectively. No difference in bleeding events was found.
Conclusion
This trial confirms prior data showing that the conventional dosage of 3,000 IU aXa is effective and safe for the prevention of venous thromboembolic events after hip replacement surgery.
doi:10.1186/1477-9560-10-10
PMCID: PMC3441324  PMID: 22713698
18.  Barriers to cardiovascular risk prevention and management in Germany – an analysis of the EURIKA study 
Background and purpose
Despite the availability of risk engines to determine cardiovascular risk, risk factor control is suboptimal. Using EURIKA data we compared risk factor control in Germany with that of 11 other European countries (rest of Europe [ROE]) to identify differences and opportunities for improvement.
Methods
EURIKA was a multinational, cross-sectional study in 12 European countries including Germany from May 2009 to January 2010. Physicians’ attitudes to risk factor control based on the 2007 European guidelines on cardiovascular disease (CVD) prevention in a representative cohort of 7641 primary care outpatients aged ≥50 years with no CV disease and at least one major CV risk factor were determined.
Results
Compared to the ROE, German physicians were more frequently male (72.7% vs 62.6%), had a higher mean age (51.7 ± 8.4 vs 47.0 ± 9.7 years), faced higher patient loads (37.9% vs 16.5% had >199 patients/week), and involved other health sector professionals (dieticians, psychologists) less (31.8% vs 41.0% in the ROE). The European Society of Cardiology (ESC) guidelines on CVD prevention were more important for German physicians (60.6% vs 55.9%), while those who didn’t use them gave reasons for nonuse as too many (62.5% vs 46.2%), too confusing, unrealistic, or not applicable to their patients. Risk engines were used less (54.5% vs 70.7%), with perceived lack of time (65.5% vs 60.2%) a frequent reason for nonuse. Risk factor control in German patients was inadequate (control rates: hypertension 36.3%, dyslipidemia 30.4%, type 2 diabetes 40.6%, obesity 28.8%) but largely comparable to other ROE countries; however, physicians tended to overestimate control rates.
Conclusion
EURIKA provides comprehensive data on the status of primary prevention of CVD in clinical practice in Germany and reveals considerable potential for improving the primary prevention of CVD.
doi:10.2147/VHRM.S29915
PMCID: PMC3333468  PMID: 22536072
cardiovascular risk factor; primary care
19.  Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study 
Background
Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice.
Methods
Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group.
Results
A total of 2,011 patients were enrolled (mean age 69.1 ± 10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p < 0.05). Both treatments were equally effective in reducing BP (14.7 ± 18.0/8.5 ± 8.2 mmHg and 12.7 ± 18.1/7.0 ± 8.3 mmHg) at the 4 year follow-up (p < 0.001 vs. baseline; p = n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p = 0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p < 0.05; AE 26.6 vs. 25.6%; p = n.s).
Conclusions
Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.
doi:10.1186/1475-2840-11-1
PMCID: PMC3313888  PMID: 22230104
20.  Hypertension Control and Cardiometabolic Risk: A Regional Perspective 
Background. We investigated the association between blood pressure control and common cardiometabolic risk factors from a global and regional perspective. Methods. In the present analysis of a large cross-sectional i-SEARCH study, 17.092 outpatients receiving antihypertensive treatment were included in 26 countries. According to clinical guidelines for the management of arterial hypertension, patients were classified based on the level of seated systolic/diastolic blood pressure (SBP/DBP). Uncontrolled hypertension was defined as SBP/DBP ≥140/90 mmHg for non-diabetics, and ≥130/80 mmHg for diabetics. Results. Overall, mean age was 63.1 years, 52.8% were male, and mean BMI was 28.9 kg/m2. Mean SBP/DBP was 148.9/87.0 mmHg, and 76.3% of patients had uncontrolled hypertension. Diabetes was present in 29.1% with mean HbA1c of 6.8%. Mean LDL-cholesterol was 3.2 mmol/L, HDL-cholesterol 1.3 mmol/L, and triglycerides 1.8 mmol/L; 49.0% had hyperlipidemia. Patients with uncontrolled hypertension had a higher BMI (29.4 versus 28.6 kg/m2), LDL-cholesterol (3.4 versus 3.0 mmol/L), triglycerides (1.9 versus 1.7 mmol/L), and HbA1c (6.8 versus 6.7%) than those with controlled blood pressure (P < 0.0001 for all parameters). Conclusions. Among outpatients treated for arterial hypertension, three quarters had uncontrolled blood pressure. Elevated SBP/DBP and uncontrolled hypertension were associated with increasing BMI, LDL-cholesterol, triglycerides, and HbA1c, both globally and regionally.
doi:10.1155/2012/925046
PMCID: PMC3254169  PMID: 22242212
21.  Office and ambulatory blood pressure control with a fixed-dose combination of candesartan and hydrochlorothiazide in previously uncontrolled hypertensive patients: results of CHILI CU Soon 
Background
Fixed-dose combinations of candesartan 32 mg and hydrochlorothiazide (HCTZ) have been shown to be effective in clinical trials. Upon market entry we conducted a noninterventional study to document the safety and effectiveness of this fixed-dose combination in an unselected population in primary care and to compare blood pressure (BP) values obtained during office measurement (OBPM) with ambulatory blood pressure measurement (ABPM).
Methods
CHILI CU Soon was a prospective, noninterventional, noncontrolled, open-label, multicenter study with a follow-up of at least 10 weeks. High-risk patients aged ≥18 years with previously uncontrolled hypertension were started on candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ. OBPM and ABPM reduction and adverse events were documented.
Results
A total of 4131 patients (52.8% male) with a mean age of 63.0 ± 11.0 years were included. BP was 162.1 ± 14.8/94.7 ± 9.2 mmHg during office visits at baseline. After 10 weeks of candesartan 32 mg/12.5 mg or 25 mg HCTZ, mean BP had lowered to 131.7 ± 10.5/80.0 ± 6.6 mmHg (P < 0.0001 for both comparisons). BP reduction was comparable irrespective of prior or concomitant medication. In patients for whom physicians regarded an ABPM to be necessary (because of suspected noncontrol over 24 hours), ABP at baseline was 158.2/93.7 mmHg during the day and 141.8/85.2 mmHg during the night. At the last visit, BP had significantly reduced to 133.6/80.0 mmHg and 121.0/72.3 mmHg, respectively, resulting in 20.8% being normotensive over 24 hours (<130/80 mmHg). The correlation between OBPM and ABPM was good (r = 0.589 for systolic BP and r = 0.389 for diastolic BP during the day). Of those who were normotensive upon OBPM, 35.1% had high ABPM during the day, 49.3% were nondippers, and 3.4% were inverted dippers. Forty-nine adverse events (1.19%) were reported, of which seven (0.17%) were regarded as serious.
Conclusion
Candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ is safe and effective for further BP lowering irrespective of prior antihypertensive drug class not being able to control BP.
doi:10.2147/VHRM.S26887
PMCID: PMC3253769  PMID: 22241950
ambulatory blood pressure; office blood pressure; normalization; response
22.  Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY 
BMC Cancer  2011;11:316.
Background
Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.
Methods
Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.
Results
1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).
Conclusions
Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.
Trial Registration
clinicaltrials.gov, NCT00451412
doi:10.1186/1471-2407-11-316
PMCID: PMC3161035  PMID: 21791091
23.  Antidiabetic pharmacotherapy and anamnestic hypoglycemia in a large cohort of type 2 diabetic patients - an analysis of the DiaRegis registry 
Background
We aimed to identify predictors of anamnestic hypoglycaemia in type-2 diabetic patients on oral mono- or dual oral combination antidiabetic pharmacotherapy.
Methods
DiaRegis is a prospective registry in type-2 diabetic patients in primary care. Odds ratios (OR) with 95% confidence intervals were determined from univariate logistic regression. Using multivariate logistic regression analysis with stepwise backward selection at an alpha of 0.05 independent predictors of hypoglycaemia were determined.
Results
3,808 patients had data on hypoglycaemia available (median age 65.9 years, 46.6% female). 10.8% had at least one anamnestic hypoglycaemic episode within the previous 12 months. Patients with hypoglycaemia received more sulfonylureas (OR 2.16; 95%CI 1.75-2.67) and less metformin (OR 0.64; 95%CI 0.50-0.82). On top of metformin, patients with thiazolidine (OR 0.50; 95%CI 0.28-0.89) and DPP-4 inhibitor use (OR 0.34; 95%CI 0.16-0.70) had a decreased risk for hypoglycaemia while it was again increased with sulfonylureas (OR 2.08; 95%CI 1.44-2.99). Age < 65 years was an independent predictor of a reduced hypoglycaemia incidence (OR 0.76; 95%CI 0.59-0.96), low HbA1c (OR 1.68; 95%CI 1.31-2.14), stroke/TIA (OR 1.72; 95%CI 1.08-2.72), heart failure (OR 1.77; 95%CI 1.28-2.45), and the use of sulfonylureas (OR 2.58; 95%CI 2.03-3.29) were independent predictors of increased risk.
Conclusions
The results indicate that the risk of hypoglycaemia might be substantially reduced by carefully selecting antidiabetic pharmacotherapy in patients with type-2 diabets in primary care.
doi:10.1186/1475-2840-10-66
PMCID: PMC3162488  PMID: 21756359
24.  The Adverse Events and Hemodynamic Effects of Adenosine-Based Cardiac MRI 
Korean Journal of Radiology  2011;12(4):424-430.
Objective
We wanted to prospectively assess the adverse events and hemodynamic effects associated with an intravenous adenosine infusion in patients with suspected or known coronary artery disease and who were undergoing cardiac MRI.
Materials and Methods
One hundred and sixty-eight patients (64 ± 9 years) received adenosine (140 µg/kg/min) during cardiac MRI. Before and during the administration, the heart rate, systemic blood pressure, and oxygen saturation were monitored using a MRI-compatible system. We documented any signs and symptoms of potential adverse events.
Results
In total, 47 out of 168 patients (28%) experienced adverse effects, which were mostly mild or moderate. In 13 patients (8%), the adenosine infusion was discontinued due to intolerable dyspnea or chest pain. No high grade atrioventricular block, bronchospasm or other life-threatening adverse events occurred. The hemodynamic measurements showed a significant increase in the heart rate during adenosine infusion (69.3 ± 11.7 versus 82.4 ± 13.0 beats/min, respectively; p < 0.001). A significant but clinically irrelevant increase in oxygen saturation occurred during adenosine infusion (96 ± 1.9% versus 97 ± 1.3%, respectively; p < 0.001). The blood pressure did not significantly change during adenosine infusion (systolic: 142.8 ± 24.0 versus 140.9 ± 25.7 mmHg; diastolic: 80.2 ± 12.5 mmHg versus 78.9 ± 15.6, respectively).
Conclusion
This study confirms the safety of adenosine infusion during cardiac MRI. A considerable proportion of all patients will experience minor adverse effects and some patients will not tolerate adenosine infusion. However, all adverse events can be successfully managed by a radiologist. The increased heart rate during adenosine infusion highlights the need to individually adjust the settings according to the patient, e.g., the number of slices of myocardial perfusion imaging.
doi:10.3348/kjr.2011.12.4.424
PMCID: PMC3150669  PMID: 21852902
MRI; Adenosine; Coronary artery disease; Hemodynamics; Adverse events
25.  Candesartan cilexetil/hydrochlorothiazide combination treatment versus high-dose candesartan cilexetil monotherapy in patients with mild to moderate cardiovascular risk (CHILI Triple T) 
Background:
Candesartan cilexetil has been shown to effectively reduce blood pressure and cardiovascular risk. Whether it is advantageous to combine candesartan cilexetil with low-dose hydrochlorothiazide (HCTZ) or uptitrate it in cases of insufficient blood pressure control has not been fully investigated under routine clinical conditions.
Methods:
CHILI Triple T is a prospective, noninterventional, observational study. Patients with uncontrolled hypertension and added cardiovascular risk received a fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg (combination therapy group) or high-dose monotherapy with candesartan cilexetil 32 mg (high-dose monotherapy group).
Results:
A total of 4600 patients with a mean age of 63.1 ± 11.0 years, of which 44.7% were female, was included. The combination therapy group had 3337 patients, and the high-dose monotherapy group 1263 patients. Patients in both treatment groups were comparable with respect to age and gender, but patients receiving high-dose monotherapy had a slightly higher mean systolic blood pressure, more prior revascularizations, renal insufficiency, diabetic nephropathy, peripheral artery disease, and a lower ankle brachial index. The use of combination therapy resulted in a blood pressure reduction of −28.5 ± 13.8/−14.2 ± 9.4 mm Hg (P < 0.001 vs 160.2 ± 13.3/94.5 ± 8.2 mm Hg at baseline). The use of high-dose monotherapy reduced blood pressure by −29.73 ±15.3/−14.1 ± 9.6 mm Hg (P < 0.001 vs 162.4 ± 14.7/94.7 ±8.7 mm Hg at baseline). Differences in subgroups of patients defined by age, gender, body mass index, dyslipidemia, waist circumference, smoking, prior cardiovascular event, glomerular filtration rate, and microalbuminuria were minor, although partially significant. Tolerability was excellent, with only 28 out of 3358 patients (0.8%) in the combination therapy group and 15 out of 1273 patients (1.2%) in the high-dose monotherapy group experiencing any adverse event, of which one in each group was considered to be serious (<0.1%).
Conclusions:
Both the fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg and high-dose monotherapy with candesartan 32 mg were highly effective in lowering blood pressure in patients at increased cardiovascular risk. Tolerability was excellent. The choice of either strategy therefore largely depends on the principal aim: blood pressure reduction with pronounced volume restriction or pronounced additional end-organ protection.
doi:10.2147/VHRM.S17004
PMCID: PMC3049544  PMID: 21415922
essential hypertension; combination therapy; high-dose monotherapy; candesartan cilexetil; noninterventional study; diuretics; Phase IV

Results 1-25 (45)