TOOLS FOR PRACTICE

Acetylsalicylic acid for primary

prevention of cardiovascular events
Paul Fritsch MD Michael R. Kolber MD CCFP MSc

Clinical question • Cancer mortality, including colon cancer mortality,

Is acetylsalicylic acid (ASA) effective in reducing was either unchanged1,2 or increased with ASA.4
cardiovascular (CV) events in patients without pre- • Up to 47% of adults older than 45 use ASA, predomi-
existing CV disease (CVD)? nantly for primary CV prevention.6
• In secondary prevention, ASA benefits outweigh risks.7
Bottom line
Three recent large RCTs of moderate-risk, elderly, Implementation
and diabetic patients do not support the use of ASA Primary CVD prevention should focus on proven lifestyle
for primary prevention. The potential absolute bene- and pharmacologic therapies, rather than ASA. Smoking
fit of about 1% is offset by a similar increase in major cessation is most effective, reducing CVD by more
bleeding. All-cause and cancer mortality were either than 50%.8 Weekly exercise (150 minutes) can reduce
unchanged or increased with ASA. CV mortality by up to 37% compared with no exercise.9
Mediterranean diets can reduce CV events by about 25%,10
Evidence while statins reduce CV events by 25% to 35%, depending
There were 3 high-quality, placebo-controlled RCTs of on dose.11 Treating hypertension can reduce CV events by
100 mg per day of ASA. about 20% per 10 mm Hg reduction, depending on base-
• One followed 12 546 patients at moderate CV risk (10- line blood pressure.12 Reductions are relative and benefits
year risk of 10% to 20% [mean 17%]).1 Patients were depend on baseline risk. Practitioners should use calcula-
predominantly men (71%); mean age was 64 years. tors13 to estimate CV risk and benefit of interventions.
-After 5 years, there was no difference in composite Dr Fritsch is a family medicine resident at the University of Calgary in Alberta. Dr Kolber is
Professor with the PEER (Patients, Experience, Evidence, Research) Group in the Department of
CV events (4.3% vs 4.5% for placebo). The mortality Family Medicine at the University of Alberta in Edmonton.
rate was 2.6% in each arm. Competing interests
None declared
-M ajor gastrointestinal bleeds increased with ASA
The opinions expressed in Tools for Practice articles are those of the authors and do not necessar-
(0.3% vs 0.1% for placebo; number needed to harm ily mirror the perspective and policy of the Alberta College of Family Physicians.
[NNH] of 345). References
1. Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, et al. Use of aspirin
• One followed 15 480 patients with diabetes (94% had to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease
type 2) and a mean age of 63 years; 63% were men.2 (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018;392(10152):1036-46.
2. ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G,
-After 7.4 years, ASA patients had decreased com- et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med
2018;379(16):1529-39.
posite CV events (8.5% vs 9.6% for placebo; number 3. McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, et al. Effect of aspirin on
cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379(16):1509-18.
needed to treat of 91) and increased fatal or major 4. McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, et al. Effect of aspirin on all-cause
bleeding (4.1% vs 3.2% for placebo; NNH = 112). mortality in the healthy elderly. N Engl J Med 2018;379(16):1519-28.
5. Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular
-There was no difference in all-cause mortality or events and bleeding events: a systematic review and meta-analysis. JAMA 2019;321(3):277-87.
6. Williams CD, Chan AT, Elman MR, Kristensen AH, Miser WF, Pignone MP, et al. Aspirin use among
cancer incidence. adults in the US: results of a national survey. Am J Prev Med 2015;48(5):501-8.
7. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention
• Another followed 19 114 elderly patients (median age of vascular disease: collaborative meta-analysis of individual participant data from randomised
74 years) primarily from Australia.3,4 After 4.7 years (trial trials. Lancet 2009;373(9678):1849-60.
8. Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE. The effects of a smoking cessa-
stopped for futility), ASA patients had no difference in tion intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med 2005;142(4):233-9.
9. Zhao M, Veeranki SP, Li S, Steffen LM, Xi B. Beneficial associations of low and large doses of
composite CV events (3.5% vs 3.9% for placebo).3 leisure time physical activity with all-cause, cardiovascular disease and cancer mortality: a
national cohort study of 88,140 US adults. Br J Sports Med 2019 Mar 19. Epub ahead of print.
-There were increases in fatal or major bleeds (3.8% 10. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, ArÓs F, et al. Primary prevention of car-
vs 2.8% for placebo3; NNH = 98), all-cause mortality diovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.
N Engl J Med 2018;378(25):e34.
(5.9% vs 5.2% for placebo4; NNH = 143), and cancer 11. Allan GM, Lindblad AJ, Comeau A, Coppola J, Hudson B, Mannarino M, et al. Simplified lipid
guidelines. Prevention and management of cardiovascular disease in primary care. Can Fam
deaths (3.1% vs 2.3% for placebo4; NNH = 125). Physician 2015;61:857-67 (Eng), e439-50 (Fr).
12. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lower-
ing for prevention of cardiovascular disease and death: a systematic review and meta-analysis.
Context Lancet 2016;387(10022):957-67.
13. McCormack J, Pfiffner P. The absolute CVD risk/benefit calculator. Vancouver, BC: Best Science Medicine;
• A recent systematic review found similar results.5 2017. Available from: http://chd.bestsciencemedicine.com/calc2.html. Accessed 2019 Mar 31.

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing
medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated
by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to
[email protected]. Archived articles are available on the ACFP website: www.acfp.ca.

480 Canadian Family Physician | Le Médecin de famille canadien } Vol 65: JULY | JUILLET 2019