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Summary of the evidence: aspirin for the primary prevention of cardiovascular events |
Hayden M, Pignone M, Phillips C, Mulrow C |
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Authors' objectives To examine the benefits and harms of aspirin for the primary prevention of cardiovascular events in patients without a previous history of cardiovascular disease (CVD).
Searching MEDLINE was searched from 1966 to May 2001; the search terms were reported. The authors also reviewed the bibliographies of other relevant articles and systematic reviews, and sought advice from experts in the field.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) of at least one year in duration were eligible for inclusion. Three of the included studies used a placebo control; the others had no placebo control. The duration of therapy in the trials ranged from 3.6 to 6.8 years.
Specific interventions included in the reviewStudies that compared aspirin with placebo or no aspirin were eligible for inclusion. The included trials used aspirin at a dose of between 75 and 500 mg/day. Four of the included studies also gave participants additional therapies: one study gave beta-carotene to 50% of the participants, one study gave warfarin to its participants, one study gave felodipine with or without an angiotensin-converting enzyme inhibitor or beta-blocker to its participants, and one study gave vitamin E to its participants.
Participants included in the reviewStudies in which less than 10% of the participants had no previous history of CVD, including myocardial infarction (MI), stroke, angina, transient ischaemic attack or peripheral vascular disease, were eligible for inclusion. The actual participants included in the primary studies were male physicians (2 studies), men at high risk of heart disease (1 study), men and women with a diastolic blood-pressure of 100 to 115 mmHg (1 study), and men and women with more than one major risk factor for coronary heart disease (CHD; 1 study). The average age of the participants, as reported by 3 studies, ranged from 53 to 61.5 years.
Outcomes assessed in the reviewStudies that measured the outcomes of MI, stroke and mortality were eligible for inclusion. The authors also reviewed the harms of aspirin, in terms of haemorrhagic stroke or gastrointestinal bleeding. However, they included prior meta-analyses in this section of the review, which is beyond the scope of DARE, therefore this abstract focuses on the review of the benefits of aspirin therapy.
How were decisions on the relevance of primary studies made?Two reviewers independently reviewed the abstracts of articles to assess their relevance to the review. The same reviewers then examined the full articles and determined eligibility by consensus. Any disagreements were resolved by discussion among all reviewers, after review of the full text.
Assessment of study quality The quality of the included studies was assessed based on the methods of randomisation, blinding, intention-to-treat analysis, follow-up rates, and crossover of assigned interventions. The authors did not state how the papers were assessed for quality, or how many reviewers performed the quality assessment.
Data extraction In the abstract of the review, the authors stated that one reviewer extracted data from the primary studies and a second reviewer checked the accuracy of the data; any discrepancies were resolved by consensus. However, in an appendix to the review, the authors stated that two reviewers independently abstracted data from the included studies and any disagreements were resolved by consensus.
Unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the outcomes of individual trials. In some cases, where different methods of categorisation were reported, the authors of the primary studies had to be contacted to determine the actual numbers of certain events.
Methods of synthesis How were the studies combined?The studies were combined using the random-effects model of DerSimonian and Laird. The authors used their best estimates of the benefits of aspirin to model its impact on populations with different risk levels for CVD. The benefits were estimated using the ORs calculated from the meta-analyses. The estimates were based on 1,000 people receiving aspirin for 5 years, using 95% CIs from the meta-analyses.
How were differences between studies investigated?The authors used graphs of outcomes and the Mantel-Haenszel chi-squared test to assess heterogeneity. A subgroup analysis was performed using only trials considered to be of good quality. The authors also examined subgroups of women, the elderly, and patients with hypertension or diabetes.
Results of the review Five RCTs that examined the benefits of aspirin were included in the review. There were 53,043 participants in total, of which 11,414 were female.
Three studies of the benefits of aspirin were rated as good quality, while two were rated as fair quality.
Participants taking aspirin were statistically significantly less likely to have a MI or to die of CHD than those not taking aspirin (OR 0.72, 95% CI: 0.60, 0.87). However, there was significant heterogeneity between the study results (chi-squared 8.07, P=0.089) as one of the 5 studies found no difference in the rate of MI between the intervention and control groups. Aspirin also appeared to reduce the odds of CHD mortality (OR 0.87, 95% CI: 0.70, 1.09) and all-cause mortality (OR 0.93, 95% CI: 0.84, 1.02), although these results were not statistically significant. There was no difference in the total number of strokes between participants taking aspirin and those not taking aspirin (OR 1.02, 95% CI: 0.85, 1.23). These results were based on 5 RCTs.
In a subgroup analysis of the 3 good-quality studies, the reduction in total CHD events was slightly larger (OR 0.65, 95% CI: 0.56, 0.75), but other outcomes were similar to the main analysis.
Participants taking aspirin were statistically significantly more likely to suffer a major gastrointestinal bleed (OR 1.7, 95% CI: 1.4, 2.1) and also appeared to be more likely to suffer from haemorrhagic stroke (OR 1.4, 95% CI: 0.9, 2.0), but this result was not statistically significant. These latter two results were based on a published meta-analysis of the 5 RCTs.
For 1,000 patients with a 1% estimated risk of CHD events over 5 years, aspirin was estimated to prevent three MIs (range: 1 to 4), but cause one haemorrhagic stroke (range: 0 to 2) and three major gastrointestinal bleeding events (range: 2 to 4). For 1,000 patients with a 5% estimated risk of CHD events over 5 years, aspirin was estimated to prevent 14 MIs (range: 6 to 20) but cause one haemorrhagic stroke (range: 0 to 2) and three major gastrointestinal bleeding events (range: 2 to 4).
Authors' conclusions Aspirin can prevent MI but it increases the risk of gastrointestinal bleeding and appears to increase the risk of haemorrhagic stroke. The net benefit of aspirin is higher in patients at higher risk of CHD events.
CRD commentary The review question was clear in terms of the study design, participants, intervention and outcomes of interest. The search strategy was restricted to only one electronic database, but was followed up by reviewing bibliographies and contacting experts in the field. The authors also attempted to identify unpublished research and they do not appear to have applied language restrictions. Other relevant studies might have been identified if electronic databases such as EMBASE, Current Contents and grey literature databases had been searched. Attempts were made to minimise the introduction of reviewer bias and error when selecting studies for the review and abstracting their data. The studies were assessed for quality using appropriate criteria. The results of this quality assessment were used in a subgroup analysis that included only the good-quality studies.
Adequate details of the individual studies were presented and the methods used to combine the studies appear to have been appropriate. Apart from the restrictive search strategy used, this systematic review appears to have been well conducted and the authors' conclusions are supported.
Implications of the review for practice and research Practice: The authors stated that the decision about whether to use aspirin chemoprevention requires consideration of the patient's cardiovascular risk, as well as the patient's relative utility for the different clinical outcomes prevented by or caused by its use.
Research: The authors did not state any implications for further research.
Funding Agency for Healthcare Research and Quality, contract number 290-97-0011.
Bibliographic details Hayden M, Pignone M, Phillips C, Mulrow C. Summary of the evidence: aspirin for the primary prevention of cardiovascular events. Rockville, MD, USA: Agency for Health Care Policy and Research. 2002 Other publications of related interest 1. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:161-72. 2. U.S. Preventive Services Task Force. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med 2002;136:157-60. 3. Sox H. Disease prevention guidelines from the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:155-6.
Indexing Status Subject indexing assigned by CRD MeSH Aspirin /therapeutic use; Cardiovascular Diseases /prevention & Myocardial Infarction /prevention & Platelet Aggregation Inhibitors /therapeutic use; Primary Prevention; Stroke /prevention & control; control; control AccessionNumber 12002008093 Date bibliographic record published 28/02/2005 Date abstract record published 28/02/2005 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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