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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Effect of aspirin on mortality in the primary prevention of cardiovascular disease

N Raju, M Sobieraj-Teague, J Hirsh, M O'Donnell, and J Eikelboom.

Review published: 2011.

Link to full article: [Journal publisher]

CRD summary

This review concluded that aspirin prevented deaths, myocardial infarction and ischaemic stroke and increased hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease. This review was generally well conducted. However, the marginal effect detected in the pooled outcome particularly for all-cause mortality did not adequately support the authors' conclusions.

Authors' objectives

To assess the effect of aspirin on mortality in the primary prevention of cardiovascular disease.

Searching

MEDLINE, EMBASE, CINAHL and The Cochrane Library were searched from inception to May 2010. Search terms were reported. Reference lists of relevant publications were screened. A related article PubMed search was performed to identify additional relevant studies. National Institutes of Health Clinical Trials Registry was searched for unpublished studies. Experts in the field were contacted for additional relevant studies.

Study selection

Randomised controlled trials (RCTs) that compared any dose of aspirin with placebo or no aspirin treatment for prevention of cardiovascular disease in adult patients without a history of symptomatic cardiovascular disease were eligible for inclusion. Eligible studies had to report at least one of the outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and bleeding. Studies were excluded if they used aspirin in combination with a second antithrombotic agent.

In the included studies, the dosing regimen of aspirin ranged from 75mg/day to 500mg/day (most used 75mg/day to 100mg/day. The percentage of patients with hypertension ranged from 9% to 100%. The percentage of patients who were current smokers ranged from 11% to 41%. The percentage of patients with diabetes mellitus ranged from 2% to 100%. One study exclusively enrolled women and in the other studies the percentage of males ranged from 28% to 100%. Some studies included a small proportion of patients with a history of ischaemic heart disease, stroke or transient ischaemic attack. Where reported, patients' mean age in included studies ranged from 54.6 to 64.5 years. The included studies were published between 1988 and 2010.

Two reviewers independently assessed studies for inclusion, with any disagreements resolved by discussion or a third reviewer.

Assessment of study quality

The quality of included studies was assessed using criteria adapted from the Cochrane Methods Group Guidelines on Systematic Reviews of Interventions. These criteria included generation of the treatment allocation sequence, allocation concealment, blinding of participants, investigators and outcome assessors, completeness of follow-up, treatment compliance and intention-to-treat analysis.

Two reviewers independently performed study quality assessment.

Data extraction

Data were extracted on event rates to enable calculation of relative risks (RRs) with 95% confidence intervals (CIs).

Two reviewers independently performed data extraction.

Methods of synthesis

Pooled relative risks with 95% CIs were calculated using the DerSimonian-Laird random-effects model. The results obtained were compared with those obtained from a fixed-effect model. Statistical heterogeneity was assessed using X2 and I2. Potential sources of statistical heterogeneity were explored on trial populations, dose of aspirin, cointerventions, outcome definitions and trial quality. Sensitivity analyses excluded studies that used aspirin at a dose of greater than 150mg/day, studies published before 2000 and studies with a high risk of bias. Publication bias was assessed using the Begg's adjusted-rank correlation test.

Results of the review

Nine RCTs were included in the review (100,076 participants). Mean follow-up duration in the included studies ranged from 3.8 to 10.1 years. Six trials were double-blinded and three trials were open label. All trials reported the process of sequence generation and concealment of allocation. Blinding of outcome assessors was adequate in all studies. Loss to follow-up rates ranged from less than 1% to 7.6%. Treatment adherence ranged from 50% to 93%. All studies used an intention-to-treat analysis.

Compared with placebo/no aspirin treatment, aspirin was associated with a marginally significant reduction in all-cause mortality (RR 0.94, 95% CI 0.88 to 1.00; nine trials) and myocardial infarction (RR 0.83, 95% CI 0.69 to 1.00; nine trials). It was associated with a significant reduction in ischaemic stroke (RR 0.86, 95% CI 0.75 to 0.98; eight RCTs) and the composite of myocardial infarction, stroke and cardiovascular death (RR 0.88, 95% CI 0.83 to 0.94; nine RCTs), but did not reduce cardiovascular mortality (RR 0.96, 95% CI, 0.84 to1.09; nine trials). Aspirin significantly increased the risk of hemorrhagic stroke (RR 1.36, 95% CI 1.01 to 1.82; eight trials), major bleeding (RR 1.66, 95% CI 1.41 to 1.95; seven trials) and gastrointestinal bleeding (RR 1.37, 95% CI 1.15 to 1.62; eight trials).

Significant heterogeneity was observed in the outcomes of myocardial infarction (I2=71%) and gastrointestinal bleeding (I2=62%). Sensitivity analyses did not materially alter the results. There was no evidence of publication bias.

Authors' conclusions

Aspirin prevented deaths, myocardial infarction and ischaemic stroke and increased hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.

CRD commentary

This review's inclusion criteria were clear. Relevant databases were searched. Efforts were made to find published and unpublished studies, which minimised potential for publication bias. The authors did not report whether language restrictions were applied in the search, which made it difficult to assess the risk of language bias. Sufficient attempts were made to minimise reviewer biases and errors in the review process.

Appropriate criteria were used to assess study quality and study quality was taken into account in the analysis. Statistical heterogeneity was assessed and appropriate methods were used to pool the results. Potential sources of statistical heterogeneity were adequately explored.

This review was generally well conducted. However, the marginal effect detected in the pooled outcome particularly for all-cause mortality did not adequately support the authors' conclusions.

Implications of the review for practice and research

The authors did not state any implications for practice and research.

Funding

None stated.

Bibliographic details

Raju N, Sobieraj-Teague M, Hirsh J, O'Donnell M, Eikelboom J. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. American Journal of Medicine 2011; 124(7): 621-629. [PubMed: 21592450]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Aspirin /administration & dosage /adverse effects /pharmacology; Cardiovascular Agents /administration & dosage /adverse effects /pharmacology; Cause of Death; Female; Gastrointestinal Hemorrhage /chemically induced /epidemiology; Humans; Incidence; Male; Middle Aged; Myocardial Infarction /epidemiology /mortality /prevention & control; Primary Prevention /methods; Randomized Controlled Trials as Topic; Risk Assessment; Stroke /epidemiology /mortality /prevention & control

AccessionNumber

12011004166

Database entry date

20/03/2012

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.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 21592450

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