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Aspirin for Disease Prevention: Public Policy or Personal Choice?Aspirin for Disease Prevention FREE

Colin Baigent, BM BCh, MA, MSc
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 12 April 2016.


From University of Oxford, Oxford, United Kingdom.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0576.

Requests for Single Reprints: Colin Baigent, BM BCh, MA, MSc, Clinical Trial Service Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, United Kingdom; e-mail, colin.baigent@ndph.ox.ac.uk.


Ann Intern Med. 2016;164(12):846-847. doi:10.7326/M16-0576
© 2016 American College of Physicians
Text Size: A A A

12 42016.

In this week's Annals, the U.S. Preventive Services Task Force (USPSTF) outlines its updated recommendations on the use of aspirin for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) after a mammoth review of the evidence (1). The USPSTF recommends (B recommendation) low-dose aspirin in men and women aged 50 to 59 years who have a predicted risk for myocardial infarction (MI) or stroke of at least 10% over 10 years, who do not have an increased risk for bleeding, and who are willing to take aspirin for at least 10 years. For the analogous group aged 60 to 69 years, the recommendation for aspirin is “optional” (C recommendation). The group aged 50 to 59 years at increased risk for CVD is moderately large—25% of men and 4% of women (estimates based on National Health and Nutrition Examination Survey data) (2). However, the group aged 60 to 69 years would be much larger (77% and 22% of men and women, respectively).

To assess the value of the latest recommendations, it is worth considering what new evidence has emerged since those issued in 2009. In that year, the Antithrombotic Trialists' (ATT) Collaboration reported a collaborative meta-analysis of individual-patient data from 6 primary prevention trials of 95 000 persons, which included a detailed assessment of how the cardiovascular benefits and bleeding risks compared in different prognostic groups (3). The latest recommendations from the USPSTF consider 5 more primary prevention trials of about 25 000 persons, most of whom were at low risk for CVD. The relative risk estimates for nonfatal MI (22% reduction), stroke (no significant effect), mortality (no significant effect), and serious gastrointestinal bleeding (58% increase) were almost identical to those reported by the ATT. Perhaps not surprisingly, the ATT and USPSTF both find that aspirin yields small cardiovascular benefits (that is, a reduction in nonfatal MI) and small bleeding risks (serious gastrointestinal bleeding and, much less commonly, hemorrhagic stroke); further, both find that the net benefit (cardiovascular benefit − bleeding risk) is small—about 1 to 2 fewer events per 1000 person-years. The ATT analysis showed that the absolute risks for CVD and bleeding are positively correlated, so the net benefits of aspirin are likely to remain small even among persons with several risk factors for CVD. Given that these risk factors and bleeding overlap substantially, it seems unlikely that meta-analyses that include new trials, even the ongoing trials, will yield well-defined groups in which cardiovascular and bleeding risks are uncoupled.

Judgment about the value of aspirin is altered, however, by the emergence of new evidence since 2009 stating that daily aspirin might prevent CRC (and possibly other types of cancer) (4, 5). Long-term follow-up information from 8 trials of a daily aspirin regimen indicated that such treatment may reduce the risk for CRC incidence and mortality, with benefits emerging within about 5 to 10 years (4). But many uncertainties about the effects of aspirin on cancer remain. The largest primary prevention trials of aspirin assessed alternate-day regimens. Recent long-term follow-up results from the Women's Health Study (6) suggested that 100 mg of aspirin every other day reduced the risk for CRC, with benefits emerging after 10 years, but the results of further follow-up from the Physicians' Health Study (which previously reported no effect of 325 mg of aspirin every other day on CRC after 12-year follow-up) (7) are unknown. The magnitude of the effect of aspirin on particular types of cancer and on overall cancer risk, the chronicity of any effect, and how the absolute effects of aspirin vary among individuals still need to be determined reliably. Updated analyses of data from aspirin trials, including the Physicians' Health Study, are ongoing under the auspices of the NoVA (Nonvascular Outcomes on Aspirin) Collaboration (4).

Although the work of the NoVA Collaboration will provide substantial new information, we will probably have to wait for the completion and extended follow-up of some of the large ongoing trials before the effects of aspirin on cancer among persons at low risk for CVD are sufficiently well-understood to inform primary prevention practice (Table). Over the next few years, ongoing primary prevention trials of aspirin in persons with diabetes (ACCEPT-D [Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes] and ASCEND [A Study of Cardiovascular Events in Diabetes]), those at elevated cardiovascular risk (ARRIVE [Aspirin to Reduce Risk of Initial Vascular Events] and TIPS-3 [The International Polycap Study 3]), and those aged 70 years or older (ASPREE [ASPirin in Reducing Events in the Elderly]) will report their (within-trial) findings, with almost 4000 incident cases of cancer (about 10% of which are likely to be CRC) expected to occur in the within-trial phase. As a result, they will substantially increase the currently available information on any early reduction in cancer risk. Over the next decade, increasingly reliable estimation of the long-term effects on cancer after 5 years of aspirin use in different populations should be possible if those trials can obtain reliable posttrial follow-up of incident cases of cancer and cancer deaths.

Table Jump PlaceholderTable. Ongoing Randomized Trials of Aspirin Versus Placebo in Low-Risk Populations Providing Information on Cancer Outcomes 

The incidence rates of cancer in the completed trials will vary substantially depending on geographic location and the era in which they were done (because cancer rates have historically varied over time). In comparison, however, the proportional effects of a given aspirin regimen (for example, low-dose daily aspirin) should be relatively stable, so the absolute effects of aspirin on cancer will be estimable by applying the relevant statistics from a meta-analysis of the trials to contemporary rates in any given region. Future models might consider the possibility that aspirin would be best directed at healthy persons with above-average risk for cancer (for example, those who are overweight). It will also be important to incorporate contemporary estimates of event rates for CVD, which are decreasing in many regions, and rates of gastrointestinal bleeding, which are also decreasing (perhaps in part because of Helicobacter pylori eradication and greater use of proton-pump inhibitors).

In summary, as yet the evidence from trials does not seem to merit a general recommendation for lifelong aspirin use in any specific low-risk group. Therefore, we should not rush to judgment with inadequate data. Instead, we should encourage completion (and long-term follow-up) of the ongoing trials so that the quality of the evidence in future years provides a firm foundation for public policy.

References

Bibbins-Domingo K, U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016; 164:836-45.
 
Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, et al, American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129:S49-73.
PubMed
CrossRef
 
Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al, Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009; 373:1849-60.
PubMed
CrossRef
 
Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011; 377:31-41.
PubMed
CrossRef
 
Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012; 379:1602-12.
PubMed
CrossRef
 
Cook NR, Lee IM, Zhang SM, Moorthy MV, Buring JE. Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med. 2013; 159:77-85.
CrossRef
 
Stürmer T, Glynn RJ, Lee IM, Manson JE, Buring JE, Hennekens CH. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study. Ann Intern Med. 1998; 128:713-20.
CrossRef
 

Figures

Tables

Table Jump PlaceholderTable. Ongoing Randomized Trials of Aspirin Versus Placebo in Low-Risk Populations Providing Information on Cancer Outcomes 

References

Bibbins-Domingo K, U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016; 164:836-45.
 
Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, et al, American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129:S49-73.
PubMed
CrossRef
 
Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al, Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009; 373:1849-60.
PubMed
CrossRef
 
Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011; 377:31-41.
PubMed
CrossRef
 
Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012; 379:1602-12.
PubMed
CrossRef
 
Cook NR, Lee IM, Zhang SM, Moorthy MV, Buring JE. Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med. 2013; 159:77-85.
CrossRef
 
Stürmer T, Glynn RJ, Lee IM, Manson JE, Buring JE, Hennekens CH. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study. Ann Intern Med. 1998; 128:713-20.
CrossRef
 

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