http://repub.eur.nl/res/aut/27689/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/22426/ 2009-04-01T00:00:00Z BACKGROUND AND PURPOSE: Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation. METHODS: This is an analysis of the Atrial Fibrillation Investigators database, which contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure. Outcomes included ischemic stroke, serious bleeding (intracranial hemorrhage or systemic bleeding requiring hospitalization, transfusion, or surgery), and cardiovascular events (ischemic stroke, myocardial infarction, systemic embolism, or vascular death). RESULTS: The analysis included 8932 patients and 17 685 years of observation from 12 trials. Patient age increased risk of ischemic stroke (adjusted hazard ratio per decade increase 1.45; 95% CI, 1.26 to 1.66), serious bleeding (1.61; 1.47 to 1.77), and cardiovascular events (1.43; 1.33 to 1.53). Compared with placebo, OAC and AP significantly reduced the risk of ischemic stroke (OAC, 0.36; 0.29 to 0.45; AP, 0.81; 0.72 to 0.90) and cardiovascular outcomes (OAC, 0.59; 0.52 to 0.66; AP, 0.81; 0.75 to 0.88), whereas OAC increased risk of serious bleeding (1.56; 1.03 to 2.37). The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome. Compared with placebo, the relative benefit of AP for preventing ischemic stroke decreased significantly as patients aged (P=0.01). CONCLUSIONS: As patients with atrial fibrillation age, the relative efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does not change for OAC. Because stroke risk increases with age, the absolute benefit of OAC increases as patients get older. http://repub.eur.nl/res/pub/22504/ 2002-11-01T00:00:00Z CONTEXT: Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. OBJECTIVE: To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). DESIGN: Pooled analysis of patient-level data from 6 published, randomized clinical trials. PATIENTS: A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. MAIN OUTCOME MEASURES: Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. RESULTS: Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. CONCLUSIONS: Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.