Effects of Combined Aspirin and Clopidogrel Therapy on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

BACKGROUND: Aspirin and clopidogrel monotherapies are effective treatments for preventing vascular disease. However, new evidence has emerged regarding the use of combined aspirin and clopidogrel therapy to prevent cardiovascular events. We therefore performed a comprehensive systematic review and meta-analysis to evaluate the benefits and harms of combined aspirin and clopidogrel therapy on major cardiovascular outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings to identify studies to fit our analysis. Eligible studies were randomized controlled trials assessing the effect of combined aspirin and clopidogrel therapy compared with aspirin or clopidogrel monotherapy. We identified 7 trials providing data with a total of 48248 patients. These studies reported 5134 major cardiovascular events, 1626 myocardial infarctions, 1927 strokes, and 1147 major bleeding events. Overall, the addition of aspirin to clopidogrel therapy as compared to single drug therapy resulted in a 9% RR reduction (95%CI, 2 to 17) in major cardiovascular events, 14% RR reduction (95%CI, 3 to 24) in myocardial infarction, 16% RR reduction (95%CI, 1 to 28) in stroke, and 62% RR increase (95%CI, 26 to 108) in major bleeding events. We also present the data as ARR to explore net value as the reduction in cardiovascular events. Overall, we observed that combined therapy yielded 1.06% decrease (95%CI, 0.23% to 1.99%) in major cardiovascular events and 1.23% increase (95%CI, 0.52% to 2.14%) in major bleeding events. CONCLUSION/SIGNIFICANCE: Although the addition of aspirin to clopidogrel resulted in small relative reductions in major cardiovascular events, myocardial infarction, and stroke, it also resulted in a relative increase in major bleeding events. In absolute terms the benefits of combined therapy, a 1.06% reduction in major cardiovascular events, does not outweigh the harms, a 1.23% increase in major bleeding events

Do characteristics of practices and general practitioners influence the yield of diabetes screening in primary care? The ADDITION Netherlands study

Objective. To investigate whether the yield of population-based diabetes screening is influenced by characteristics of the general practitioner ( GP) and the practice. Design. Cross-sectional study. Setting. Seventy-nine general practices in the south-western region of the Netherlands. Subjects. From 2002 to 2004, 56 978 people were screened for diabetes. GPs completed a questionnaire containing items on the GP ( age, gender, employment, special interest in diabetes, providing insulin therapy) and the practice ( setting, location, number of patients from ethnic minority groups, specific diabetes clinic, involvement of practice assistant, practice nurse or diabetes nurse in diabetes care). Main outcome measures. The ratio screen-detected diabetic patients/known diabetic patients per practice ( SDM/KDM) and the number of detected diabetic patients per practice adjusted for practice size and age distribution ( SDM per standardized practice). Results. The yield of screening per practice varied widely. Higher age of the GP ( regression coefficient 0.20; 95% confidence interval, CI 0.07-0.34), urban location ( -4.60; 95% CI -6.41 to -2.78) and involvement of the practice assistant ( 2.27; 95% CI 0.49-4.06) were independently associated with SDM/KDM. Using the other outcome variable, results were similar. Additionally, cooperation with a diabetes nurse was associated with a lower yield. Conclusion. A lower yield of screening, reflecting a lower prevalence of undiagnosed diabetes, was found in practices of younger GPs and in urban practices. A lower yield was not associated with an appropriate practice organization regarding diabetes care nor with a specialty of the GP in diabetes. The wide variation in the yield of screening stresses the importance of a screening programme in each general practice

Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention.

In patients with manifestations of cardiovascular disease, acetylsalicylic acid (popularly known as aspirin) has been the mainstay of treatment for decades owing to its capacity to reduce the risk of ischaemic events. Accordingly, novel antithrombotic therapies have been traditionally tested on a background of acetylsalicylic acid therapy. Although the adjunctive use of such antithrombotic therapies can potentially further reduce the risk of ischaemic events, these agents are also inevitably associated with an increased risk of bleeding. However, acetylsalicylic acid also increases the risk of bleeding, challenging the paradigm that this agent should remain the cornerstone of antiplatelet treatment when alternative antithrombotic agents are also used. Many antithrombotic compounds are characterized by increased potency and consistent efficacy, which might lessen the need for concomitant acetylsalicylic acid. Accordingly, numerous investigations are testing the hypothesis that acetylsalicylic acid-sparing regimens based on newer antithrombotic agents might have an increased net benefit for individual patients owing to the reduction in bleeding risk, without a trade-off in efficacy. This Review summarizes the state of the art relating to antithrombotic approaches with and without acetylsalicylic acid for the prevention of cardiovascular disease and cardioembolic stroke. Discussion of the scientific rationale, from bench to bedside, for ongoing studies of acetylsalicylic acid-free pharmacological strategies is included