Andrew Dunn, MD
In patients with atrial fibrillation, do the effectiveness and safety of oral anticoagulant (OAC) and antiplatelet (AP) therapies for stroke prevention change with age?
Individual patient data meta-analysis of 12 randomized controlled trials (RCTs). 6 RCTs were placebo-controlled; 8 RCTs compared an OAC with an AP.
Outcome adjudication committee was blinded in 11 trials.
Mean 2 years.
8932 adults (mean age 72 y, 63% men) with nonvalvular atrial fibrillation. Patients with clinical indications for or against any of the active therapies were excluded.
Full-dose OACs (mainly warfarin sodium or 4-hydroxycoumarin) with lower target international normalized ratio (INR) of 1.5 to 2.8 and upper target INR of 2.7 to 4.2 (n = 3430); APs (mainly acetylsalicylic acid, 75 to 325 mg) with or without low-dose OACs (median INR < 1.5) (n = 3531); or placebo (n = 1971).
Ischemic stroke, serious bleeding, and cardiovascular events (ischemic stroke, myocardial infarction, systemic embolism, or vascular death). Intention-to-treat analysis.
Older age was associated with increased risk for all outcomes (Table). Independent of age and other covariates, both OACs and APs decreased risk for stroke and cardiovascular events compared with placebo; OACs, but not APs, increased risk for serious bleeding (Table). The treatment effect of OACs decreased slightly in older patients: The adjusted hazard ratio for ischemic stroke with OAC use was 0.22 (95% CI 0.11 to 0.41) at age 50 years and 0.53 (CI 0.35 to 0.81) at age 90 years (P for interaction 0.07). In contrast, the treatment effect of APs decreased considerably in older patients: The adjusted hazard ratio for ischemic stroke with AP use was 0.40 (CI 0.22 to 0.72) at age 50 years, gradually increasing until it exceeded 1 at about age 82 years and reaching 1.25 at age 90 years (P for interaction 0.01). Age did not influence the effect of treatment with either drug on serious bleeding or cardiovascular events.
In patients with atrial fibrillation, the effectiveness of antiplatelet therapy for stroke prevention decreased substantially with age, but that of oral anticoagulants did not. Relative risk for serious bleeding with oral anticoagulants was not affected by age.
Oral anticoagulant (OAC) and antiplatelet (AP) therapies for stroke prevention in patients with atrial fibrillation*
*CI defined in Glossary. Hazard ratios adjusted for age, treatment, sex, previous stroke or transient ischemic attack, diabetes, hypertension, heart failure, and year of study.
Dunn A. Oral anticoagulant therapy safely prevented stroke in older patients with atrial fibrillation. Ann Intern Med. ;151:JC1–4. doi: 10.7326/0003-4819-151-2-200907210-02004
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Published: Ann Intern Med. 2009;151(2):JC1-4.
Cardiology, Geriatric Medicine, Neurology, Prevention/Screening, Rhythm Disorders and Devices.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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