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1.  Clinical Characteristics, Management, and Control of Permanent vs. Nonpermanent Atrial Fibrillation: Insights from the RealiseAF Survey 
PLoS ONE  2014;9(1):e86443.
Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.
Methods and Results
Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS2 score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS2 score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke.
Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart failure, adequate rate control is an important target for improving the management of permanent atrial fibrillation patients.
PMCID: PMC3908888  PMID: 24497948
2.  Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-Analysis 
Clopidogrel, one of the most commonly prescribed medications, is a pro-drug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes.
In patients treated with clopidogrel, to define the risk of major adverse cardiovascular outcomes among carriers of one (∼26% prevalence in whites) and carriers of two (∼2% prevalence in whites) reduced-function CYP2C19 variants.
Data Sources and Study Selection
A literature search was conducted (January 2000-August 2010) of the MEDLINE, Cochrane, and EMBASE databases. Genetic studies were included where clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and where clinical outcomes were ascertained.
Data Extraction
Investigators from nine studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and their 95% confidence intervals (CI) for specific cardiovascular outcomes by genotype.
Among 9685 patients [91.3% of whom underwent percutaneous coronary intervention (PCI) and 54.5% of whom had an acute coronary syndrome (ACS)], 863 experienced the composite endpoint of cardiovascular death, myocardial infarction, or stroke; 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were non-carriers, 26.3% had one, and 2.2% had two CYP2C19 reduced-function alleles. A significantly increased risk of the composite endpoint was evident in both carriers of one (HR 1.55, 95% CI 1.11-2.27, P=0.01) and two (HR 1.76, 95% CI 1.24-2.50, P=0.002) CYP2C19 reduced-function alleles. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of one (HR 2.67, 95% CI 1.69-4.22, P<0.0001) and two (HR 3.97, 95% CI 1.75-9.02, P=0.001) CYP2C19 reduced-function alleles.
Among patients treated with clopidogrel for PCI, carriage of even one reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis.
PMCID: PMC3048820  PMID: 20978260
3.  One-year costs associated with cardiovascular disease in Canada: Insights from the REduction of Atherothrombosis for Continued Health (REACH) registry 
The Canadian Journal of Cardiology  2010;26(8):e297-e305.
To provide a contemporary estimate of the economic burden of atherothrombosis in Canada, annual cardiovascular-related hospitalizations, medication use and associated costs across the entire spectrum of atherothrombotic disease were examined.
The REduction of Atherothrombosis for Continued Health (REACH) registry enrolled 1964 Canadian outpatients with coronary artery disease, cerebrovascular disease or peripheral arterial disease (PAD), or three or more cardiovascular risk factors. Baseline data on cardiovascular risk factors and associated medication use, and one-year follow-up data on cardiovascular events, hospitalizations, procedures and medication use were collected. Annual hospitalization and medication costs (Canadian dollars) were derived and compared among patients according to the presence of established atherothrombotic disease at baseline, specific arterial beds affected and the number of affected arterial beds.
Average annualized medication costs were $1,683, $1,523 and $1,776 for patients with zero, one, and two or three symptomatic arterial beds, respectively. Average annual hospitalization costs increased significantly with the number of beds affected ($380, $1,403 and $3,465, respectively; P<0.0001 for overall linear trend). Mean hospitalization costs for patients with any coronary artery disease, any cerebrovascular disease and any PAD were $1,743, $1,823 and $4,677, respectively. After adjusting for other clinical factors, PAD at baseline was independently associated with a significant increase in hospitalization costs.
Costs associated with vascular-related hospitalizations and interventions for Canadian patients increased with the number of affected arterial beds, and were particularly high for patients with PAD and/or polyvascular disease. These contemporary data provide insight into the economic burden associated with atherothrombotic disease in Canada, and highlight the need for increased preventive strategies to lessen the burden for patients and society.
PMCID: PMC2954538  PMID: 20931098
Cerebrovascular disease; Coronary disease; Costs; Hospitalization; Peripheral vascular disease
5.  Smoking, Clopidogrel, and Mortality in Patients with Established Cardiovascular Disease 
Circulation  2009;120(23):2337.
Smoking increases platelet aggregability, and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests. Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown.
Methods and Results
We evaluated the relationship between smoking status (current smoker (CS), former smoker (FS), and never smoker (NS)) and treatment with clopidogrel on the risk of all-cause, cardiovascular, and cancer mortality among the 12,152 participants from the CHARISMA trial with established cardiovascular disease. Current smoking was associated with an increase in all-cause (adjusted hazard ratio [HR] 2.58, [1.85–3.60]), cardiovascular (HR 2.26, [1.48–3.45]), and cancer mortality (HR 4.16, [2.46–7.03]) compared to NS. The impact of clopidogrel and mortality differed by smoking status (P for interaction = 0.018 for current smokers). Among CS, clopidogrel was associated with a reduction in all-cause mortality (HR 0.68, [0.49–0.94]); clopidogrel did not reduce all cause mortality among FS (HR 0.95, [0.75–1.19]) or NS (HR 1.14, [0.83–1.58]). A similar pattern was noted for cardiovascular mortality. As expected, no relationship was observed between clopidogrel and cancer mortality by smoking status. The risk of bleeding seemed to differ according to smoking status; randomized clopidogrel was associated with a significantly increased hazard of severe or moderate bleeding (HR 1.62, P=0.04) among CS, but a smaller and nonsignificant increase among NS (HR 1.31, P=0.15).
Clopidogrel therapy may be more effective, but with a greater bleeding risk in CS than in patients who are not smokers. Further studies are needed to investigate this possibility.
PMCID: PMC2814172  PMID: 19933933
Smoking; Clopidogrel; Mortality; Cardiovascular disease
6.  Causes of death in early MI survivors with persistent infarct artery occlusion: results from the Occluded Artery Trial (OAT) 
OAT randomised patients with an occluded infarct artery three to 28 days after myocardial infarction (MI). The study demonstrated that PCI did not reduce the occurrence of the primary composite endpoint of death, re-MI, and New York Heart Association class IV heart failure in comparison with patients assigned to optimal medical therapy alone (MED). In view of prior literature in similar cohorts showing fewer sudden cardiac deaths and less left ventricular (LV) remodelling, but excess re-MI with PCI, causes of death were analysed in more detail.
Methods and results
Stepwise Cox regression was used to examine baseline variables associated with causes of death. The immediate and primary cause of death did not differ between 1,101 PCI and 1,100 MED patients. One-year cardiovascular death rates were 3.8% for the PCI group, and 3.7% for the MED group, and 0.9% per year for the next four years in both groups. Five of six cases of cardiac rupture occurred in patients undergoing PCI.
In stable post-MI patients with occlusion of the infarct-related artery, PCI did not change the rate or cause of death. The observation that the majority of cardiac ruptures occurred in patients undergoing PCI deserves further investigation.
PMCID: PMC2893563  PMID: 20142183
Myocardial infarction; causes of death; percutaneous coronary intervention; cardiac rupture
7.  Coronary Intervention for Persistent Occlusion after Myocardial Infarction 
The New England journal of medicine  2006;355(23):2395-2407.
It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events.
We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure.
The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P = 0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P = 0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P = 0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization).
PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction. ( number, NCT00004562.)
PMCID: PMC1995554  PMID: 17105759

Results 1-7 (7)