Research Not Supportive of Taking Low-Dose Aspirin Solely for Cancer Prevention

For more than a century, the nonsteroidal anti-inflammatory drug (NSAID) aspirin has been a common household medication for alleviating fever and pain in adults. There are two common strengths of this drug: regular dose (325 milligram [mg], brand names include BAYER ASPIRIN,[1] ECOTRIN[2] and VAZALORE)[3] and low dose (ranging from 75 to 162.5 mg, brand names include BAYER LOW ASPIRIN,[4] DURLAZA[5] and ECOTRIN).[6] It also is sometimes found in combination drugs, such as those containing antacids and medications for allergies, colds or pain.

In recent decades, low-dose aspirin has been promoted for preventing cardiovascular disease (including angina, heart attack and stroke) and various types of cancer (particularly colorectal cancer).

In the July 2020 issue of Worst Pills, Best Pills News, we presented recent evidence demonstrating that — consistent with the approved use of low-dose aspirin by the Food and Drug Administration (FDA) — the benefits of regular use of the drug outweigh its risks only for preventing another heart attack or stroke in patients who have already experienced a heart attack or stroke, have other evidence of cardiovascular disease, or have a history of a coronary artery bypass operation or related procedure (secondary prevention).[7],[8] In contrast, the benefits of regular low-dose aspirin use do not outweigh its risks for preventing a first heart attack or stroke in patients without cardiovascular disease (primary prevention).

In this article, we discuss key evidence supporting the conclusion that low-dose aspirin should not be used for the sole purpose of preventing any type of cancer, an indication for which the drug is not approved by the FDA.

Colorectal cancer

Most recent studies that assessed possible cancer-prevention benefits of aspirin have focused on colorectal cancer.

Although a 2016 federally funded systematic review of clinical trials in which aspirin was taken to prevent cardiovascular disease concluded the drug is effective for reducing the rate of colorectal cancer, this benefit did not occur until after ten years of regular use of the drug.[9] Specifically, the review estimated that based on evidence from four clinical trials, aspirin is associated with an approximately 20% reduction in colorectal cancer risk over an approximately 20-year period of regular aspirin use.

However, the review did not find conclusive evidence that aspirin reduced deaths due to colorectal cancer. Further, it did not weigh aspirin’s benefits against the risks of potentially serious adverse effects from such prolonged use of the drug. Notably, the main adverse effect of aspirin is major bleeding, including bleeding from the gastrointestinal tract or other sites (such as the nose) and, less commonly but more dangerously, bleeding in the brain.[10]

In fact, a 2015 analysis of long-term follow-up data from more than 27,900 subjects aged 45 or older enrolled in the Women’s Health Study — a randomized placebo-controlled trial of alternate-day (every-other-day) low-dose aspirin use —— found that the drug had a modest decrease in 15-year risk of colorectal cancer.[11] However, for the majority of women, this benefit was offset by an increased risk of major gastrointestinal bleeding requiring hospitalization.

Although the analysis of the Women’s Health Study suggested that aspirin’s benefits may outweigh its risks for colorectal-cancer prevention in “select” women aged 65 or older, this finding was not confirmed by the August 2020 findings from ASPREE — a randomized placebo-controlled trial of daily low-dose aspirin involving more than 19,000 Australian and U.S. subjects aged 70 or older without cardiovascular disease.[12] The new findings showed that after a median five years of follow-up, subjects taking low-dose aspirin had a modestly greater risk of being diagnosed with advanced cancer and increased risk of dying from advanced colorectal cancer.

Additional evidence is pending from another trial called ARRIVE.[13],[14] This trial is tracking colorectal and other cancer outcomes in more than 12,500 subjects (men aged 55 years or older and women aged 60 years or older) without prior cardiovascular disease or diabetes but who had a moderate risk of cardiovascular disease, such as high cholesterol and current smoking. These subjects were randomized to receive either low-dose aspirin or placebo.

Other cancers

There is only limited evidence supporting the benefit of low-dose aspirin for reducing the risk of noncolorectal cancer, including breast, lung, pancreatic and ovarian cancer.[15]

In fact, the evidence showing that aspirin reduces these cancers and related death comes from a small set of studies conducted by a single investigative team.[16] Moreover, combined analyses from multiple studies, such as the aforementioned 2016 review,[17] do not support the use of aspirin to prevent noncolorectal cancer.

The analysis of the Women’s Health Study data found no benefit for aspirin use for preventing noncolorectal cancer after 15 years of follow-up.[18] For most women, the drug increased the risk of gastrointestinal bleeding.

Moreover, the ASPREE trial showed that aspirin users actually had more deaths from solid tumors (including breast, lung and prostate cancer as well as melanoma) than those taking a placebo.[19]

Finally, findings from a 2018 analysis of ASCEND — another large, randomized placebo-controlled trial of low-dose aspirin — found no significant differences between aspirin and placebo users in terms of gastrointestinal tract cancer or all cancers.[20] Over an average of seven years, this trial followed nearly 15,500 subjects aged 40 or older who had diabetes but did not have cardiovascular disease.

Other considerations

There is no agreement among researchers about the mechanism through which the drug supposedly reduces cancer risk.[21] Some researchers suggest that the decision to use aspirin for cancer prevention should be individualized according to age, sex and others patient factors.[22] Generally, even those who attribute cancer-prevention benefits to aspirin do not recommend its universal use for this purpose[23] in older adults until further research provides more robust evidence.

What You Can Do

Do not self-medicate with aspirin or any other drug to prevent cancer. Instead, talk to your doctor about your cancer risks and try to lower your chance of developing cancer by not smoking, limiting or avoiding alcohol intake, eating healthy foods and being physically active.[24] It also is important to undergo regular cancer screening exams. For example, colonoscopy can detect colorectal cancer in its earliest stages or can identify precancerous growths that can be removed before they develop into cancer. Do not start or stop taking aspirin on a regular basis without consulting your doctor first.
 

References

[1] Bayer HealthCare LLC. Label: aspirin (BAYER ASPIRIN). May 2017. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0c6ae05f-7634-34d1-e054-00144ff88e88&type=display. Accessed January 7, 2021.

[2] Medtech Products Inc. Label: regular-dose aspirin (ECOTRIN). February 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=36cb530b-25b2-4f62-a25d-aa04360815a8&type=display. Accessed January 7, 2020.

[3] PLx Pharma, Inc. Label: aspirin (VAZALORE). December 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203697Orig1s004lbl.pdf. Accessed January 7, 2021.

[4] Bayer HealthCare LLC. Label: aspirin (BAYER LOW-DOSE ASPIRIN). September 2017. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=075b103e-0bb4-4b7a-ac0e-5645bcbd0a07&type=display. Accessed January 7, 2021.

[5] New Haven Pharmaceuticals. Label: aspirin extended release (DURLAZA). September 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/200671s000lbl.pdf. Accessed January 7, 2021.

[6] Medtech Products Inc. Label: aspirin (ECOTRIN). April 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=222d187b-aae6-410b-baeb-b2bd42f5c676&type=display. Accessed January 7, 2021.

[7] Daily low-dose aspirin should not be used to prevent a first heart attack or stroke. Worst Pills, Best Pills News. July 2020. /newsletters/view/1344. Accessed January 7, 2021.

[8] Food and Drug Administration. Use of aspirin for primary prevention of heart attack and stroke. May 2, 2014. https://www.fda.gov/drugs/drug-information-consumers/use-aspirin-primary-prevention-heart-attack-and-stroke. Accessed January 7, 2021.

[9] Chubak J, Whitlock EP, Williams SB, et al. Aspirin for the prevention of cancer incidence and mortality: Systematic evidence reviews for the U.S. preventive services task force. Ann Intern Med. 2016;164(12):814-825.

[10] Spencer FA, Guyatt G, Tampi M, Golemiec B. Aspirin in the primary prevention of cardiovascular disease and cancer. UpToDate. Aug 31, 2020.

[11] van Kruijsdijk RCM, Visseren FLJ, Ridker PM, et al. Individualised prediction of alternate-day aspirin treatment effects on the combined risk of cancer, cardiovascular disease and gastrointestinal bleeding in healthy women. Heart. 2015;101(5):369-376.

[12] McNeil JJ, Gibbs P, Orchard SG, et al. Effect of aspirin on cancer incidence and mortality in older adults. J Natl Cancer Inst. 2020;djaa114(Aug 11). doi:10.1093/jnci/djaa114.

[13] Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018;392(10152):1036-1046.

[14] Hawk ET, Maresso KC. The ASPREE trial: An unanticipated stimulus for greater precision in prevention? J Natl Cancer Inst. 2020;113(3):djaa115.

[15] Spencer FA, Guyatt G, Tampi M, Golemiec B. Aspirin in the primary prevention of cardiovascular disease and cancer. UpToDate. Aug 31, 2020.

[16] Ibid.

[17] Chubak J, Whitlock EP, Williams SB, et al. Aspirin for the prevention of cancer incidence and mortality: Systematic evidence reviews for the U.S. preventive services task force. Ann Intern Med. 2016;164(12):814-825.

[18] van Kruijsdijk RCM, Visseren FLJ, Ridker PM, et al. Individualised prediction of alternate-day aspirin treatment effects on the combined risk of cancer, cardiovascular disease and gastrointestinal bleeding in healthy women. Heart. 2015;101(5):369-376.

[19] McNeil JJ, Gibbs P, Orchard SG, et al. Effect of aspirin on cancer incidence and mortality in older adults. J Natl Cancer Inst. 2020;djaa114(Aug 11). doi:10.1093/jnci/djaa114.

[20] Bowman L, Mafham M, Wallendszus K, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379(16):1529-1539.

[21] Sankaranarayanan R, Kumar DR, Altinoz MA, Bhat GJ. Mechanisms of colorectal cancer prevention by aspirin—a literature review and perspective on the role of cox-dependent and -independent pathways. Int J Mol Sci. 2020;21(23):9018.

[22] Perisettia A, Goyalb H, Thariana B, et al. Aspirin for prevention of colorectal cancer in the elderly: friend or foe? Ann Gastroenterol. 2021;34(1):1-11.

[23] Jiang Y, Su Z, Wang R, et al. Aspirin and risk of different cancers: an umbrella meta-analysis. Ann Transl Med. 2020;8(20):1333.

[24] National Institutes of Health, National Cancer Institute. Cancer prevention overview (PDQ)–health professional version. October 7, 2020. https://www.cancer.gov/about-cancer/causes-prevention/hp-prevention-overview-pdq. Accessed January 7, 2021.