Stroke Prevention in Atrial Fibrillation Study. Final results.
TL;DR: Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation and patients with nonrheumatic atrialfibrillation who can safely take either aspirin or warfarIn should receive prophylactic antithrombotic therapy to reduce the risk of stroke.
Abstract: BACKGROUND Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.
METHODS AND MAIN RESULTS The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.
CONCLUSIONS Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.
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TL;DR: It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced in the detection, management, and management of diseases.
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It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced in the detection, management,
8,362 citations
TL;DR: This document summarizes current research, plans, and recommendations for future research, as well as providing a history of the field and some of the techniques used, currently in use, at the National Institutes of Health.
Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair
Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect
Nancy M. Albert, PhD, RN, FAHA
Biykem Bozkurt, MD, PhD, FACC, FAHA
Ralph G. Brindis, MD, MPH, MACC
Mark A. Creager, MD, FACC, FAHA[#][1]
Lesley H. Curtis, PhD, FAHA
David DeMets, PhD[#][1]
Robert A
6,967 citations
4,960 citations
TL;DR: An updated meta-analysis of all currently available randomized trials that extends observations about the efficacy and safety of antithrombotic therapies for preventing stroke in patients who have atrial fibrillation is presented.
Abstract: Hart and colleagues provide an update of a previous meta-analysis of antithrombotic agents for stroke prevention in patients with atrial fibrillation. The updated meta-analysis shows that, compared...
4,265 citations
TL;DR: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate- control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate -control strategy.
Abstract: Background There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. Methods We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. Results A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. Conclusions Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.
3,988 citations
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TL;DR: In this article, the product-limit (PL) estimator was proposed to estimate the proportion of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t).
Abstract: In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed. For random samples of size N the product-limit (PL) estimate can be defined as follows: L...
52,450 citations
TL;DR: The development of chronic atrial fibrillation was associated with a doubling of overall mortality and of mortality from cardiovascular disease and among the risk factors for cardiovascular disease, diabetes and electrocardiographic evidence of left ventricular hypertrophy were related to the occurrence of atrialfibrillation.
Abstract: In the Framingham Study 2325 men and 2866 women 30 to 62 years old at entry were followed biennially over 22 years for the development of chronic atrial fibrillation in relation to antecedent cardiovascular disease and risk factors. During surveillance, atrial fibrillation developed in 49 men and 49 women. The incidence rose sharply with age but did not differ significantly between the sexes. Overall, there was a 2.0 per cent chance that the disorder would develop in two decades. Atrial fibrillation usually followed the development of overt cardiovascular disease. Only 18 men and 12 women (31 per cent) had chronic atrial fibrillation in the absence of cardiovascular disease. Cardiac failure and rheumatic heart disease were the most powerful predictive precursors, with relative risks in excess of sixfold. Hypertensive cardiovascular disease was the most common antecedent disease, largely because of its frequency in the general population. Among the risk factors for cardiovascular disease, diabetes and electrocardiographic evidence of left ventricular hypertrophy were related to the occurrence of atrial fibrillation. The development of chronic atrial fibrillation was associated with a doubling of overall mortality and of mortality from cardiovascular disease.
2,381 citations
TL;DR: Controlled trials of anticoagulants or antiarrhythmic agents in persons with chronic AF may demonstrate if strokes can be prevented in this highly susceptible group.
Abstract: Chronic atrial fibrillation (AF) as a precursor of stroke was assessed over 24 years of follow-up of the general population sample at Framingham, Massachusetts. Persons with chronic established AF, with or without rheumatic heart disease (RHD), are at greatly increased risk of stroke, and the stroke is probably due to embolism. Chronic AF in the absence of RHD is associated with more than a fivefold increase in stroke indicence, while AF with RHD has a 17-fold increase. Stroke occurrence increased as duration of AF increased, with no evidence of a particularly vulnerable period. Chronic idiopathic AF is an important precursor of cerebral embolism. Controlled trials of anticoagulants or antiarrhythmic agents in persons with chronic AF may demonstrate if strokes can be prevented in this highly susceptible group.
1,452 citations
TL;DR: It is concluded that lone atrial fibrillation in patients under the age of 60 at diagnosis is associated with a very low risk of stroke, and routine anticoagulation may not be warranted.
Abstract: From 1950 to 1980, 3623 patients from Olmsted County, Minnesota, were found to have atrial fibrillation. Ninety-seven of these patients (2.7 percent), who were 60 years old or younger at diagnosis, had lone atrial fibrillation (atrial fibrillation in the absence of overt cardiovascular disease or precipitating illness), and their data were reviewed to determine the incidence of thromboemboli. Twenty of these patients (21 percent) had an isolated episode of atrial fibrillation, 56 (58 percent) had recurrent atrial fibrillation, and 21 (22 percent) had chronic atrial fibrillation. The total follow-up period was 1440 person-years, with a mean of 14.8 years per patient. The mean age at diagnosis was 44 years. Nineteen cardiovascular events occurred in 17 patients; 4 patients had strokes thought to be due to emboli from atrial fibrillation, and 4 had myocardial infarctions without overt evidence of previous coronary artery disease. The probability of survival at 15 years was 94 percent among the patients with lone atrial fibrillation. At 15 years, 1.3 percent of the patients had had a stroke on a cumulative actuarial basis. On an actuarial basis, there was no difference in survival or in survival free of stroke among the patients with the three types of lone atrial fibrillation (i.e., isolated, recurrent, and chronic). We conclude that lone atrial fibrillation in patients under the age of 60 at diagnosis is associated with a very low risk of stroke. This suggests that routine anticoagulation may not be warranted.
928 citations
TL;DR: Long-term therapy with warfarin has an important beneficial effect after myocardial infarction and can be recommended in the treatment of patients who survive the acute phase.
Abstract: Background and Methods. The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infarction has been highly controversial. We therefore randomly assigned 1214 patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) to treatment with warfarin (607 patients) or placebo (607 patients) for an average of 37 months (range, 24 to 63). Results. At the end of the treatment period, there had been 123 deaths in the placebo group and 94 in the warfarin group — a reduction in risk of 24 percent (95 percent confidence interval, 4 to 44 percent; P = 0.027). A total of 124 patients in the placebo group had reinfarctions, as compared with 82 in the warfarin group — a reduction of 34 percent (95 percent confidence interval, 19 to 54 percent; P = 0.0007). Furthermore, we observed a reduction of 55 percent (95 percent confidence interval, 30 to 77 percent) in the number of total cerebrovascular accidents in th...
607 citations