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ACTIVE A: Adding clopidogrel to aspirin does not affect mortality in AF
The rate of all-cause mortality, including vascular and nonvascular death, did not differ in patients with atrial fibrillation who were treated with aspirin plus clopidogrel or aspirin alone, according to results of the ACTIVE A study published in The American Journal of Cardiology.
Kanjana S. Perera, MBBS, investigator of the Stroke and Cognition Program at the Population Health Research Institute in Hamilton, Ontario; assistant professor in the division of neurology at McMaster University in Hamilton; and director of the inpatient acute stroke program at Hamilton Health Sciences, and colleagues analyzed data from 7,554 patients (mean age, 71 years; 58% men) with AF and at least one additional risk factor for stroke who were unsuitable for anticoagulation with warfarin. Patients were assigned to 75 mg per day of clopidogrel plus aspirin (n = 3,772) or aspirin monotherapy (n = 3,782).
Information that was reviewed included clinical characteristics, participant demographics, hypertension severity, CAD, BP and estimated glomerular filtration rate. Outcomes of interest were all-cause mortality, vascular death and nonvascular death. Patients were followed up for a median of 3.7 years.
During follow-up, 22% of patients died at an annualized mortality rate of 6.4% per year. Both treatment arms had similar mortality rates.
The groups did not differ in all-cause mortality, (HR = 0.99; 95% CI, 0.9-1.1), vascular death or nonvascular death.
BMI less than 25 kg/m2 (HR = 1.4; 95% CI, 1.3-1.6), Latin American ethnicity (HR = 1.5; 95% CI, 1.3-1.7) and increased resting heart rate (HR per 30 bpm = 1.3; 95% CI, 1.1-1.4) were independent predictors of all-cause mortality.
Other independent predictors included diabetes (HR = 1.4; 95% CI, 1.3-1.6), advancing age (HR per 10-year increase = 1.6; 95% CI, 1.5-1.7), peripheral artery disease (HR = 1.8; 95% CI, 1.4-2.2), previous stroke or transient ischemic attack (HR = 1.4; 95% CI, 1.3-1.6), CAD (HR = 1.2; 95% CI, 1.1-1.3), lower diastolic BP (HR per 20 mm Hg decrease = 1.3; 95% CI, 1.1-1.4), left ventricular systolic dysfunction (HR for moderate = 1.5; 95% CI, 1.2-1.7; HR for severe = 1.8; 95% CI, 1.5-2.2), HF (HR = 1.6; 95% CI, 1.4-1.8), reduced estimated glomerular filtration rate (HR for below 40 mL/min/1.73m2 = 1.6; 95% CI, 1.4-1.8) and a hemoglobin level less than 13 mg/dL (HR = 1.4; 95% CI, 1.2-1.5).
“The absolute reduction in fatal strokes by dual antiplatelet therapy (n = 23) was offset partially by an increase of fatal bleeding (n = 15),” Perera and colleagues wrote. “Even nonfatal serious bleeding, increased by dual antiplatelet therapy, initiates a series of events that are associated with later death, and this likely accounts for the null overall effect of dual antiplatelet therapy on mortality. Fatal stroke accounts for only a small fraction of total mortality in anticoagulated patients with AF.” – by Darlene Dobkowski
Disclosures: The main trial was funded by Bristol-Myers Squibb and Sanofi-Aventis. The authors report no relevant financial disclosures.