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Acetylsalicylic acid for primary prevention of cardiovascular events


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


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 toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Acetylsalicylic acid for primary

prevention of cardiovascular events

Paul Fritsch MD Michael R. Kolber MD CCFP MSc

Clinical question

Is acetylsalicylic acid (ASA) effective in reducing cardiovascular (CV) events in patients without pre- existing CV disease (CVD)?

Bottom line

Three recent large RCTs of moderate-risk, elderly, and diabetic patients do not support the use of ASA for primary prevention. The potential absolute bene- fit of about 1% is offset by a similar increase in major bleeding. All-cause and cancer mortality were either unchanged or increased with ASA.


There were 3 high-quality, placebo-controlled RCTs of 100 mg per day of ASA.

• One followed 12 546 patients at moderate CV risk (10- year risk of 10% to 20% [mean 17%]).


Patients were predominantly men (71%); mean age was 64 years.

- After 5 years, there was no difference in composite CV events (4.3% vs 4.5% for placebo). The mortality rate was 2.6% in each arm.

- Major gastrointestinal bleeds increased with ASA (0.3% vs 0.1% for placebo; number needed to harm [NNH] of 345).

• One followed 15 480 patients with diabetes (94% had type 2) and a mean age of 63 years; 63% were men.


- After 7.4 years, ASA patients had decreased com-

posite CV events (8.5% vs 9.6% for placebo; number needed to treat of 91) and increased fatal or major bleeding (4.1% vs 3.2% for placebo; NNH = 112).

- There was no difference in all-cause mortality or cancer incidence.

• Another followed 19 114 elderly patients (median age 74 years) primarily from Australia.


After 4.7 years (trial stopped for futility), ASA patients had no difference in composite CV events (3.5% vs 3.9% for placebo).


- There were increases in fatal or major bleeds (3.8%

vs 2.8% for placebo


; NNH = 98), all-cause mortality (5.9% vs 5.2% for placebo


; NNH = 143), and cancer deaths (3.1% vs 2.3% for placebo


; NNH = 125).


• A recent systematic review found similar results.


• Cancer mortality, including colon cancer mortality, was either unchanged


or increased with ASA.


• Up to 47% of adults older than 45 use ASA, predomi- nantly for primary CV prevention.


• In secondary prevention, ASA benefits outweigh risks.



Primary CVD prevention should focus on proven lifestyle and pharmacologic therapies, rather than ASA. Smoking cessation is most effective, reducing CVD by more than 50%.


Weekly exercise (150 minutes) can reduce CV mortality by up to 37% compared with no exercise.


Mediterranean diets can reduce CV events by about 25%,


while statins reduce CV events by 25% to 35%, depending on dose.


Treating hypertension can reduce CV events by about 20% per 10 mm Hg reduction, depending on base- line blood pressure.


Reductions are relative and benefits depend on baseline risk. Practitioners should use calcula- tors


to estimate CV risk and benefit of interventions.

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 Family Medicine at the University of Alberta in Edmonton.

Competing interests None declared

The opinions expressed in Tools for Practice articles are those of the authors and do not necessar- ily mirror the perspective and policy of the Alberta College of Family Physicians.


1. Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, 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):1036-46.

2. ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379(16):1529-39.

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.

4. McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, et al. Effect of aspirin on all-cause 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 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 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 of vascular disease: collaborative meta-analysis of individual participant data from randomised 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- 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 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.

10. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, ArÓs F, et al. Primary prevention of car- diovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.

N Engl J Med 2018;378(25):e34.

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 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.

Lancet 2016;387(10022):957-67.

13. McCormack J, Pfiffner P. The absolute CVD risk/benefit calculator. Vancouver, BC: Best Science Medicine;

2017. Available from: http://chd.bestsciencemedicine.com/calc2.html. Accessed 2019 Mar 31.


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