Applied Evidence

Aspirin for primary prevention: USPSTF recommendations for CVD and colorectal cancer

J Fam Pract. 2019 April;68(3):146-151

References

1. FDA. Use of aspirin for primary prevention of heart attack and stroke. https://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm390574.htm. Accessed March 22, 2019.

2. Guirguis-Blake JM, Evans CV, Senger CA, et al. Aspirin for the primary prevention of cardiovascular events: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:804-813.

3. Whitlock EP, Burda BU, Williams SB, et al. Bleeding risks with aspirin use for primary prevention in adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:826-835.

4. 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;164:814-825.

5. Dehmer SP, Maciosek MV, Flottemesch TJ, et al. Aspirin for the primary prevention of cardiovascular disease and colorectal cancer: a decision analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:777-786.

6. Bibbins-Domingo K. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164:836-845.

7. Baigent C, Blackwell L, Colins R, et al; Antithrombotic Trialists (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participation data from randomised trials. Lancet. 2009:373:1849-1860.

8. Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014;312:2510-2520.

9. Rothwell PM, Cook NR, Gaziano JM, et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet. 2018;392:387-399.

10. Bowman L, Mafham M, Wallendszus K, et al; ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379:1529-1539.

11. McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379:1509-1518.

12. 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;392:1036-1046.

13. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illness, operations, and medications: case control results from Melbourne Colorectal Cancer Study. Cancer Res. 1988;48:4399-4404.

14. Sutcliffe P, Connock M, Gurung T, et al. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol Assess. 2013;17:1-253.

15. Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378:2081-2087.

16. Gamba CA, Swetter SM, Stefanick ML, et al. Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: the Women’s Health Initiative. Cancer. 2013;119:1562-1569.

17. Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.

18. Risch H, Lu L, Streicher SA, et al. Aspirin use and reduced risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2016;26:68-74.

19. McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379:1519-1528.

20. Hernández-Díaz S, Rodríguez LA. Incidence of serious upper gastrointestinal bleeding/perforation in the general population: review of epidemiologic studies. J Clin Epidemiol. 2002;55:157-163.

21. Guirguis-Blake JM, Evans CV, Senger CA, et al. Aspirin for the primary prevention of cardiovascular events: a systematic evidence review for the U.S. Preventive Services Task Force. Evidence Synthesis no 131. Rockville, MD: Agency for Healthcare Research and Quality; 2015. https://www.ncbi.nlm.nih.gov/books/NBK321623/. Accessed March 22, 2019.

22. De Berardis G, Lucisano G, D’Ettorre A, et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA. 2012;307:2286-2294.

23. Thorat MA, Cuzick J. Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population. Eur J Epidemiol. 2015;30:5-18.

24. Hernández-Díaz S, García Rodríguez LA. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med. 2006;4:22.

25. Huang ES, Strate LL, Ho WW, et al. Long term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. 2011:124;426-433.

26. Walker J, Robinson J, Stewart J, et al. Does enteric-coated aspirin result in a lower incidence of gastrointestinal complications compared to normal aspirin? Interact Cardiovasc Thorac Surg. 2007:6;519-522.

27. NIH. Aspirin dosing: a patient-centric trial assessing benefits and long-term effectiveness (ADAPTABLE). https://clinicaltrials.gov/ct2/show/NCT02697916. Accessed March 22, 2019.

28. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J. 2016;37:2315-2381.

29. ADA. Standards of medical care in diabetes – 2017. Diabetes Care. 2017;40(suppl 1). http://care.diabetesjournals.org/content/diacare/suppl/2016/12/15/40.Supplement_1.DC1/DC_40_S1_final.pdf. Accessed March 22, 2019.

30. Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl):e637S-e668S.

31. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. J Am Col Cardiol. 2019. doi: https://doi.org/10.1016/j.jacc.2019.03.010. Accessed March 22, 2019.

32. Mora S, Manson JE. Aspirin for primary prevention of atherosclerotic cardiovascular disease: advances in diagnosis and treatment. JAMA Intern Med. 2016;176:1195-1204.

One major limiting factor is that most data come from CVD prevention trials, and only a limited number of trials have focused specifically on cancer prevention. For the USPSTF, these data showed no statistically significant risk reduction in overall cancer mortality (RR = 0.96; 95% CI, 0.87-1.06) or in total cancer incidence (RR = 0.98; 95% CI, 0.93-1.04).⁴ Other ongoing trials may yield more definitive data.¹⁴

The particular interest in CRC was due to it being the first cancer found to be preventable with aspirin therapy. The USPSTF, while acknowledging the homogeneous nature of supporting studies, noted that their significant number and resulting evidence made CRC the only cancer warranting evaluation. Population studies have now shown more benefit than the few randomized control trials. The Women’s Health Study and the Physicians’ Health Study were both limited by their duration. But such studies conducted over a longer period revealed notable benefits in the second decade of use, with a statistically significant lower CRC incidence (RR = 0.60; 95% CI, 0.47-0.76). Additionally, CRC mortality at 20 years was decreased in patients taking aspirin regularly (RR = 0.67; 95% CI, 0.52-0.86).⁴ Multiple studies are in progress to better establish aspirin’s CRC benefit.

While not directly applicable to the general population, use of aspirin for patients with Lynch syndrome to prevent CRC has strong supporting evidence.¹⁵ Beyond CRC, there is nascent evidence from limited observational studies that aspirin may have a preventive effect on melanoma and ovarian and pancreatic cancers.^16-18 Further studies or compilations of data would be needed to draw more significant conclusions on other types of cancers. Larger studies would prove more difficult to do, given the smaller incidences of these cancers.

Interestingly, a recent study showed that for individuals 70 years and older, aspirin might increase the risk for all-cause mortality, primarily due to increased cancer mortality across all types.¹⁹ Although this result was unexpected, caution should be used when prescribing aspirin particularly for patients 70 or older with active cancer.

A look at the harms associated with aspirin use

Aspirin has long been known to cause clinically significant bleeding. Aspirin inhibits platelet-derived cyclooxygenase-1 (COX-1), a potent vasoconstrictor, and thereby decreases platelet aggregation, reducing thromboembolic potential and prolonging bleeding time. These effects can confer health benefits but also carry the potential for risks. A decision to initiate aspirin therapy for primary prevention relies on an understanding of the benefit-to-harm balance.

Continue to: Initial aspirin studies...