ADJUSTED-DOSE WARFARIN VERSUS LOW-INTENSITY, FIXED-DOSE WARFARIN PLUSASPIRIN FOR HIGH-RISK PATIENTS WITH ATRIAL-FIBRILLATION - STROKE PREVENTION IN ATRIAL-FIBRILLATION-III RANDOMIZED CLINICAL-TRIAL

Citation
Jl. Blackshear et al., ADJUSTED-DOSE WARFARIN VERSUS LOW-INTENSITY, FIXED-DOSE WARFARIN PLUSASPIRIN FOR HIGH-RISK PATIENTS WITH ATRIAL-FIBRILLATION - STROKE PREVENTION IN ATRIAL-FIBRILLATION-III RANDOMIZED CLINICAL-TRIAL, Lancet, 348(9028), 1996, pp. 633-638
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, General & Internal
Journal title
LancetACNP
ISSN journal
0140-6736
Volume
348
Issue
9028
Year of publication
1996
Pages
633 - 638
Database
ISI
SICI code
0140-6736(1996)348:9028<633:AWVLFW>2.0.ZU;2-Z
Abstract
Background Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). Howeve r, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of throm boembolism. Methods 1044 patients with AF and with at least one thromb oembolic risk factor (congestive heart failure or left ventricular fra ctional shortening less than or equal to 25%, previous thromboembolism , systolic blood pressure of more than 160 mm Hg at study enrolment, o r being a woman aged over 75 years) were randomly assigned either a co mbination of low-intensity, fixed-dose warfarin (international normali sed ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open -labelled. Findings The mean INR during follow-up of patients taking c ombination therapy (n=521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n=523). During followup, 54% of INRs in patie nts taking combination therapy were 1.2-1.5 and 34% were less than 1.2 . The trial was stopped after a mean follow-up of 1.1 years when the r ate of ischaemic stroke and systemic embolism (primary events) in pati ents given combination therapy (7.9% per year) was significantly highe r than in those given adjusted-dose warfarin (1.9% per year) at an int erim analysis (p<0.0001), an absolute reduction of 6.0% per year (95% CI 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p=0.0007) and of primary event or vascular death (11.8% vs 6.4%, p=0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Int erpretation Low-intensity, fixed-dose warfarin plus aspirin in this re gimen is insufficient for stroke prevention in patients with non-valvu lar AF at high-risk for thromboembolism; adjusted-dose warfarin (targe t INR 2.0-3.0) importantly reduces stroke for high-risk patients.