Elsevier

The Lancet

Volume 357, Issue 9250, 13 January 2001, Pages 89-95
The Lancet

Articles
Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general Practice*

https://doi.org/10.1016/S0140-6736(00)03539-XGet rights and content

Summary

Background

In addition to the treatment of specific cardiovascular risk factors, intervention which interferes with the general mechanisms of atherosclerosis could further reduce the incidence of cardiovascular events. We aimed to investigate in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with one or more major cardiovascular risk factors.

Methods

We did a randomised controlled open 2·2 factorial trial to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in the prevention of cardiovascular events, in people with one or more of the following: hypertension, hypercholesterolaemia, diabetes, obesity, family history of premature myocardial infarction, or individuals who were elderly.

Findings

4495 people (2583 female, mean age 64·4 years) were included in the trial. After a mean follow-up of 3·6 years the trial was prematurely stopped on ethical grounds when newly available evidence from other trials on the benefit of aspirin in primary prevention was strictly consistent with the results of the second planned interim analysis. Aspirin lowered the frequency of all the endpoints, being significant for cardiovascular death (from 1·4 to 0·8%; relative risk 0·56 [95% CI 0·31–0·99]) and total cardiovascular events (from 8·2 to 6·3%; 0·77 [0·62–0·95]). Severe bleedings were more frequent in the aspirin group than the no-aspirin group (1·1% vs 0·3%; p<0·0008). Vitamin E showed no effect on any prespecified endpoint. Analyses were by intention-to-treat.

Interpretation

In women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin given in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile. The results on vitamin E's cardiovascular primary preventive efficacy are not conclusive per se, although our results are consistent with the negative results of other large published trials on secondary prevention.

Introduction

Although general practice is the natural context for primary cardiovascular prevention strategies, very rarely is this the setting of large randomised trials with protocols closely reproducing the conditions of routine care.1, 2, 3, 4

Following a collaboration in controlled and long-term observational studies5, 6, 7, 8, in 1993 a cooperative group for research in general practice planned a pragmatic trial to assess the efficacy of antiplatelet and/or antioxidant strategies in prevention of cardiovascular events in people with one or more cardiovascular risk factor but no history of cardiovascular diseases.9 These hypotheses were selected with the aim of interfering with the general mechanisms of atherosclerosis, in addition to the treatment of specific risk factors, with interventions on: the oxidative damage, claimed to be an early and permanently underlying disease-causing mechanism, with vitamin E, for which promising epidemiological evidence was not matched by controlled experimental data;10, 11 and thrombotic event, the final step of the atherosclerotic process, with aspirin, for which the evidence from healthy cohorts of UK and US medical doctors12, 13 had not been considered a sufficient basis for recommendation of its routine use in primary prevention.

Section snippets

Study design

The Primary Prevention Project (PPP) is a controlled, centrally randomised, open-label clinical trial designed to test whether chronic treatment with aspirin and vitamin E reduces the frequency of major fatal and non-fatal cardiovascular events, with no clinically relevant safety implications. Participants were both men and women aged 50 years or greater, with at least one of the major recognised cardiovascular risk factors.

Study population

Participants were screened for eligibility when they attended their

Participants and follow-up

Between 1994 and 1998, 4495 patients were recruited, 4258 (94·7%) by 315 general practitioners and 237 (5·3%) by 15 hospital hypertension units. Each general practitioner recruited an average of 14 patients (range 1–65).

Table 1 shows baseline characteristics of the population. Mean age was 64·4 (SD 7·6) years and 2583 (57·7%) of the population were women. Baseline characteristics were well balanced across the groups, with the exception of hypercholesterolaemia and mean cholesterol

Discussion

We set out to provide an assessment of antiplatelet and antioxidant agents as cardiovascular primary preventive strategies in the context of care where they are expected to be decided and practised, on people of both sexes identified as being at cardiovascular risk on the basis of at least one of the major recognised risk factors. Aspirin was beneficial with respect to all the planned endpoints, whereas the findings with vitamin E seemed to be negative.

The ethical constraints that led to

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