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

Low-dose aspirin and cancer mortality: a meta-analysis of randomized trials

EJ Mills, P Wu, M Alberton, S Kanters, A Lanas, and R Lester.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

The review concluded that non-vascular deaths, including cancer deaths, were reduced with low-dose aspirin in the short-term. The review was generally well conducted and the authors’ conclusions seem reasonable. However, the authors’ conclusions (as they recommend) should be considered alongside the risks of low-dose daily aspirin.

Authors' objectives

To determine whether low-dose aspirin reduced cancer mortality in the shorter term.

Searching

Ten databases including PubMed, Cochrane Central Register of Controlled Trails, and EMBASE were searched from inception to December 2011 for articles in any language. Search terms were reported. Reference lists of published systematic reviews were also searched.

Study selection

Randomised controlled trials (RCTs) of low-dose aspirin (75 to 325mg daily) alone in any population were eligible for inclusion. Trials had to report on non-cardiovascular disease or cancer mortality. Trials which used non-daily dosing were excluded, as were pharmacokinetic trials and trials reporting only surrogate markers of safety.

The included trials studied low-dose aspirin (38 to 325mg daily) in patients with a range of conditions, including cardiovascular disease, prostate biopsy, valve replacement, and diabetes. The control groups received no treatment or placebo. The proportion of cardiovascular heart disease ranged from 11 to 100% (where reported). The mean age of patients ranged from 53.2 to 79 years. Trials were published from 1988 to 2009.

Two reviewers independently undertook study selection.

Assessment of study quality

Trial quality was assessed using blinding, allocation concealment, randomisation, intention-to-treat analysis, and loss to follow-up greater than 20%.

Two reviewers independently undertook quality assessment.

Data extraction

Data were extracted on non-cardiovascular mortality and cancer mortality, and used to calculate relative risks (RRs) with 95% confidence intervals (CIs).

Two reviewers extracted the data into pre-piloted standardised forms.

Methods of synthesis

DerSimonian and Laird random-effects meta-analysis was used to calculate pooled relative risks and 95% confidence intervals. Ι² was used to assess statistical heterogeneity.

Meta-regression was used to determine the effects of duration and dose on effect sizes. Cumulative meta-analysis was used to estimate the period when the treatment becomes significant. Sequential analysis was conducted to determine the strength of the information.

Results of the review

Twenty-five trials (from 23 articles) were included in the review (82,868 patients); 11 trials specifically reported on cancer mortality (13, 568 patients in Table 1; 16,066 patients in text). All trials reported blinding status and intention-to treat. Twenty trials reported randomisation and sequence generation. Fifteen trials reported allocation concealment. Three trials had more than 20% losses to follow-up. The duration of follow-up ranged from one to 80 months.

Low-dose aspirin was associated with a statistically significantly lower risk on non-vascular mortality (RR 0.88, 95% CI 0.81 to 0.96; 24 trials; Ι²=0%) and cancer mortality (RR 0.77, 95% CI 0.63 to 0.95; 11 trials; Ι²=0%) compared with placebo or no treatment.

There was no significant difference in longer duration trials compared with shorter duration trials, or in trials with a higher dose compared with lower dose. Cumulative meta-regression indicated that significant effects were observed after an average of four years follow-up. Sequential analysis indicated that the optimal information size for nonvascular deaths was 33,586.

Authors' conclusions

Non-vascular deaths, including cancer deaths, were reduced with low-dose aspirin in the short-term.

CRD commentary

Inclusion criteria for the review were clearly defined. Several relevant databases were searched for articles in any language. Publication bias was not assessed, although the extensive search should have limited the risks. Attempts were made to reduce reviewer error and bias throughout the review.

Quality assessment of the included trials indicated that the quality of the evidence base was generally good. There were differences across the trials for patient characteristics. There were some discrepancies in the reporting of numbers of patients between the text and the tables. The authors noted that there was likely to be reporting bias for cancer mortality, as the trials were designed to assess cardiovascular disease outcomes. The authors also noted that the short duration of trials was likely to underestimate the effects of aspirin on cancer. Data were combined using suitable meta-analysis techniques. Statistical heterogeneity was reported.

The review was generally well conducted and the authors’ conclusions seem reasonable. However, the authors’ conclusions, as they recommend, should be considered alongside the risks of low-dose daily aspirin.

Implications of the review for practice and research

Practice: The authors stated that clinicians and pharmacists should be prepared to discuss the broad benefits and risk of aspirin beyond its traditional role in cardiovascular disease. The impact of widespread aspirin use on cancer mortality may have a large and important impact on public health.

Research: The authors stated that it was likely that longer-term trials would better determine the incidence of cancers than shorter-term trials. Individual patient data meta-analysis would enable subgroup analysis.

Funding

One author was supported through a Canada Research Chair.

Bibliographic details

Mills EJ, Wu P, Alberton M, Kanters S, Lanas A, Lester R. Low-dose aspirin and cancer mortality: a meta-analysis of randomized trials. American Journal of Medicine 2012; 125(6): 560-567. [PubMed: 22513195]

Indexing Status

Subject indexing assigned by NLM

MeSH

Anti-Inflammatory Agents, Non-Steroidal /administration & dosage; Aspirin /administration & dosage; Drug Administration Schedule; Humans; Neoplasms /mortality; Randomized Controlled Trials as Topic; Risk

AccessionNumber

12012027750

Database entry date

12/11/2012

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: 22513195