"Clopidogrel with Aspirin in High-Risk Patients with Atrial Fibrillation (ACTIVE A)". The New England Journal of Medicine. 2009. 360:2066-2078. PubMed•Full
Links to original sources: Wiki Journal Post Full Journal Article
Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading
Among patients with atrial fibrillation at increased stroke risk that are unsuitable for vitamin K antagonist therapy, does the addition of clopidogrel to aspirin reduce the risk of vascular events?
In patients with atrial fibrillation unsuitable for vitamin K antagonist therapy and at increased risk for stroke, adding clopidogrel to aspirin reduced the risk of major vascular events, particularly stroke, but increased the risk of major hemorrhage.
Atrial fibrillation increases the risk of stroke by fivefold, and adjusted-dose vitamin K antagonists (VKAs) and antiplatelet agents both reduce this risk, though VKAs are recommended for higher-risk patients. However, VKAs require regular monitoring and are unsuitable for many patients, who generally receive aspirin instead. The ACTIVE A trial evaluated the effect of adding clopidogrel to aspirin in atrial fibrillation patients at an increased risk for stroke for whom VKA therapy was unsuitable.
No specific guidelines were cited by the trial, but it was noted that VKAs are typically recommended for patients at a higher risk of stroke and aspirin for those at lower risk.
- Multicenter, double-blind, randomized, placebo-controlled trial - N=7,554 - Clopidogrel (n=3,772) vs placebo (n=3,782), plus aspirin for all patients - Median follow-up: 3.6 years - Analysis: Intention-to-treat - Primary outcome: Composite of stroke, myocardial infarction, non-CNS systemic embolism, or death from vascular causes
Inclusion Criteria: - Atrial fibrillation at enrollment or had at least two episodes in the previous 6 months - At least one risk factor for stroke (age ≥75, hypertension, previous stroke/TIA/systemic embolism, left ventricular ejection fraction <45%, peripheral artery disease, or age 55-74 plus diabetes or CAD)
Exclusion Criteria: - Required VKA or antiplatelet therapy, documented peptic ulcer disease within 6 months, history of intracerebral hemorrhage, significant thrombocytopenia, ongoing alcohol abuse
Baseline Characteristics - Mean age: 71 years - 58.2% male - Atrial fibrillation status: 63.7% permanent, 22.1% paroxysmal, 14.0% persistent - Mean CHADS2 score: 2.0
- Patients were randomly assigned to receive either 75 mg/day of clopidogrel or matching placebo, in addition to recommended aspirin dose (75-100 mg/day)
Primary Outcome - Primary composite outcome occurred in 832 patients receiving clopidogrel (6.8% per year) vs 924 patients receiving placebo (7.6% per year) [RR 0.89; 95% CI 0.81-0.98; P=0.01]
- Stroke: 296 patients with clopidogrel (2.4% per year) vs 408 placebo (3.3% per year) [RR 0.72; 95% CI 0.62-0.83; P<0.001] - Myocardial infarction: 90 patients with clopidogrel (0.7% per year) vs 115 placebo (0.9% per year) [RR 0.78; 95% CI 0.59-1.03; P=0.08] - Major bleeding: 251 patients with clopidogrel (2.0% per year) vs 162 placebo (1.3% per year) [RR 1.57; 95% CI 1.29-1.92; P<0.001]
- ACTIVE A used a relatively high dose of aspirin as the control, which may be associated with an increased risk of bleeding. - The trial has limited applicability to patients who are not at such a high risk of bleeding or who are capable of taking VKAs. Funding - Funded by grants from Sanofi-Aventis and Bristol-Myers Squibb - Authors disclosed various personal fees from these and other pharmaceutical companies
- The full text and details of the ACTIVE A trial are available on the NEJM website.