Sutcliffe, P. (Paul), Connock, M., Gurung, T., Freeman, Karoline, Johnson, Samantha Ann, Kandala, Ngianga-Bakwin, Grove, Amy L., Gurung, Binu, Morrow, Sarah, Stranges, Saverio and Clarke, Aileen (2013) Aspirin in primary prevention of cardiovascular disease and cancer : a systematic review of the balance of evidence from reviews of randomized trials. PLoS One, Volume 8 (Number 12). Article number e81970. doi:10.1371/journal.pone.0081970 ISSN 1932-6203.

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Abstract

Background:

Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses.

Methods and Findings:

Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82).

Conclusions:

Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Population, Evidence & Technologies (PET) > Warwick Evidence Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Aspirin, Cardiovascular system -- Diseases -- Treatment, Cardiovascular pharmacology, Cancer -- Treatment, Systematic reviews (Medical research)
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	2013
Dates:	Date Event 2013 Published
Volume:	Volume 8
Number:	Number 12
Page Range:	Article number e81970
DOI:	10.1371/journal.pone.0081970
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	26 December 2015
Date of first compliant Open Access:	26 December 2015
Funder:	National Institute for Health Research (Great Britain) (NIHR)
Grant number:	HTA11/130/02 (NIHR)

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