Stroke in women — from evidence to inequalities

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A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.

Paul Ridker, Nancy Cook, I-Min Lee … (2005)

Randomized trials have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women. We randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes). During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a nonsignificant reduction in risk with aspirin of 9 percent (relative risk, 0.91; 95 percent confidence interval, 0.80 to 1.03; P=0.13). With regard to individual end points, there was a 17 percent reduction in the risk of stroke in the aspirin group, as compared with the placebo group (relative risk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04), owing to a 24 percent reduction in the risk of ischemic stroke (relative risk, 0.76; 95 percent confidence interval, 0.63 to 0.93; P=0.009) and a nonsignificant increase in the risk of hemorrhagic stroke (relative risk, 1.24; 95 percent confidence interval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (relative risk, 1.02; 95 percent confidence interval, 0.84 to 1.25; P=0.83) or death from cardiovascular causes (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (relative risk, 1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older. In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point. Copyright 2005 Massachusetts Medical Society.

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Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group.

C. Belanger, Julie E Buring, C Hennekens … (1989)

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial designed to determine whether low-dose aspirin (325 mg every other day) decreases cardiovascular mortality and whether beta carotene reduces the incidence of cancer. The aspirin component was terminated earlier than scheduled, and the preliminary findings were published. We now present detailed analyses of the cardiovascular component for 22,071 participants, at an average follow-up time of 60.2 months. There was a 44 percent reduction in the risk of myocardial infarction (relative risk, 0.56; 95 percent confidence interval, 0.45 to 0.70; P less than 0.00001) in the aspirin group (254.8 per 100,000 per year as compared with 439.7 in the placebo group). A slightly increased risk of stroke among those taking aspirin was not statistically significant; this trend was observed primarily in the subgroup with hemorrhagic stroke (relative risk, 2.14; 95 percent confidence interval, 0.96 to 4.77; P = 0.06). No reduction in mortality from all cardiovascular causes was associated with aspirin (relative risk, 0.96; 95 percent confidence interval, 0.60 to 1.54). Further analyses showed that the reduction in the risk of myocardial infarction was apparent only among those who were 50 years of age and older. The benefit was present at all levels of cholesterol, but appeared greatest at low levels. The relative risk of ulcer in the aspirin group was 1.22 (169 in the aspirin group as compared with 138 in the placebo group; 95 percent confidence interval, 0.98 to 1.53; P = 0.08), and the relative risk of requiring a blood transfusion was 1.71. This trial of aspirin for the primary prevention of cardiovascular disease demonstrates a conclusive reduction in the risk of myocardial infarction, but the evidence concerning stroke and total cardiovascular deaths remains inconclusive because of the inadequate numbers of physicians with these end points.

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Sex differences in stroke epidemiology: a systematic review.

Peter Appelros, Birgitta Stegmayr, Andreas Terént (2009)

Epidemiological studies, mainly based on Western European surveys, have shown that stroke is more common in men than in women. In recent years, sex-specific data on stroke incidence, prevalence, subtypes, severity and case-fatality have become available from other parts of the world. The purpose of this article is to give a worldwide review on sex differences in stroke epidemiology. We searched PubMed, tables-of-contents, review articles, and reference lists for community-based studies including information on sex differences. In some areas, such as secular trends, ischemic subtypes and stroke severity, noncommunity-based studies were also reviewed. Male/female ratios were calculated. We found 98 articles that contained relevant sex-specific information, including 59 incidence studies from 19 countries and 5 continents. The mean age at first-ever stroke was 68.6 years among men, and 72.9 years among women. Male stroke incidence rate was 33% higher and stroke prevalence was 41% higher than the female, with large variations between age bands and between populations. The incidence rates of brain infarction and intracerebral hemorrhage were higher among men, whereas the rate of subarachnoidal hemorrhage was higher among women, although this difference was not statistically significant. Stroke tended to be more severe in women, with a 1-month case fatality of 24.7% compared with 19.7% for men. Worldwide, stroke is more common among men, but women are more severely ill. The mismatch between the sexes is larger than previously described.