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.

Initial aspirin studies did not show a statistically significant increase in bleeding, likely due to too few events and inadequate powering. Subsequent meta-analyses from multiple evaluations have consistently shown bleeding to be a risk.^3,7 The risk for bleeding with aspirin has also been examined in multiple cohort studies, which has helped elucidate the risk in greater detail.

Gastrointestinal bleeding

Epidemiologic data show that among patients who do not use nonsteroidal anti-inflammatory drugs (NSAIDs), the rate of upper gastrointestinal (GI) complications is 1 case per 1000 patient-years.²⁰ Multiple studies have consistently shown that aspirin use increases the rate of significant upper GI bleeding over baseline risk (odds ratio [OR] = 1.54-1.58).^3,21,22 Interestingly, these increases seem not to be influenced by other factors, such as comorbidities that increase the risk for ASCVD. Analysis of cancer prevention studies showed similar epidemiologic trends, with aspirin use exceeding a baseline bleeding risk of 0.7 cases of upper GI complications per 1000 patient-years (OR = 1.31-1.73).²³

Other risk factors. Evaluation of risk factors for bleeding primarily comes from 2 studies.^3,7 Most data concern the impact of individual factors on significant GI bleeding, with fewer data available for evaluating risk for intracerebral hemorrhage (ICH). Initial analysis of individual prospective studies showed little or no correlation between risk for bleeding and such factors as gender, age, or history of hypertension or ASCVD.²¹ Subsequent analysis of meta-data and large cohorts did show statistically significant impact on rates of bleeding across several factors (TABLE 1^3,7).

Enteric coating on aspirin does appear to lower the rates of gastric mucosal injury.

Of note is a large heterogeneous cohort study conducted in Spain. Data showed significant increases in baseline risk for GI bleeding in older men with a history of GI bleeding and NSAID use. The absolute risk for GI bleed in this group was potentially as high as 150 cases per 1000 patient-years, well above the risk level assumed for the average patient.²⁴ A seemingly small OR of 1.5 could dramatically increase the absolute risk for bleeding in such patients, and it suggests that a generalized risk for bleeding probably shouldn’t be applied to all patients. Individuals may be better served by a baseline risk calculation reflecting multiple factors.

Intracerebral hemorrhage

Due to the comparatively uncommon nature of ICH, fewer data are available to support definitive conclusions about its increased risk with aspirin use. Aspirin use appeared to increase the risk for ICH with ratios between 1.27 and 1.32 in meta-analyses (measured as an OR or as an RR),^3,7,21 with an IRR of 1.54 in a cohort study.²² The only statistically significant factors suspected to increase the risk of ICH at baseline were smoking (RR = 2.18) and mean BP > 20 mm Hg over normal (OR = 2.18). Age, gender, and diabetes all showed a nonsignificant trend toward risk increase.⁷

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