Tools for Practice


#231 Does an ASA a day really keep the doctor away?


CLINICAL QUESTION
Is ASA effective for reducing cardiovascular events in patients without pre-existing cardiovascular disease? 


BOTTOM LINE
Three recent large, randomized, controlled trials (RCTs) of moderate risk, elderly, and diabetic patients do not support use of ASA for primary prevention. The potential absolute benefit of ~1% (only found in one study) is offset by similar increase in major bleeding. All-cause and cancer mortality was either unchanged or increased with ASA. Routine use of ASA for primary cardiovascular prevention should be discouraged.



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EVIDENCE
Three large, high quality, placebo controlled RCTs of ASA 100 mg/day. 
  • ARRIVE: RCT of 12,546 patients at moderate cardiovascular risk [10-year risk 10-20% (mean 17%)].1 Predominantly males (70.5%), mean age 64 years. After 5 years: 
    • No difference in:  
      • Composite cardiovascular events: 4.3% versus 4.5% placebo. 
      • Mortality: 2.6% in each arm. 
    • Increased major gastrointestinal bleeds with ASA: (hemodynamic compromise or requiring transfusion) 0.3% versus 0.1% placebo; Number needed to harm (NNH)=345. 
  • ASCEND: RCT of 15,480 diabetics (94% type 2), mean age 63 years, 63% males.2After 7.4 years follow up, patients on ASA had: 
    • Decreased composite cardiovascular events: 8.5% versus 9.6% placebo, Number needed to treat (NNT)=91. 
    • Increased fatal or major (requiring hospitalization, transfusion or surgery) bleeds: 4.1% versus 3.2% placebo: NNH 112. 
    • No difference: all-cause mortality or cancer incidence. 
  • ASPREE: RCT of 19,114 elderly patients (median age 74 years) primarily from Australia.3,4After 4.7 years (trial stopped for futility), patients on ASA had:  
    • No difference in: 
      • Composite cardiovascular events: 3.5% versus 3.9% placebo.3 
    • Increased: 
      • Fatal or major bleeds: 3.8% versus 2.8% placebo;3 NNH 98. 
      • All-cause mortality: 5.9% versus 5.2% placebo;4NNH 143. 
      • Cancer deaths: 3.1% versus 2.3% placebo;4 NNH 125.  
Context: 
  • Systematic reviews published prior to and after these studies found similar results.5-7 
  • Cancer, including colon, was either unchanged1,2 or worse with ASA.4 
  • Guideline groups have different recommendations regarding ASA for primary cardiovascular prevention.8-10 
  • Up to 47% of adults over 45 years old use ASA; predominantly for primary cardiovascular prevention.11,12 
  • In secondary prevention (patients with established CVD), ASA benefits do outweigh risks.13 


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Author(s):

  • Michael R Kolber MD CCFP MSc
  • Paul Fritsch MD CCFP

1. Gaziano JM, Brotons C, Coppolecchia R, et al. Lancet. 2018; 392(10152):1036-46.

2. ASCEND Study Collaborative Group. N Engl J Med. 2018; 379(16):1529-39.

3. McNeil JJ, Wolfe R, Woods RL, et al. N Engl J Med. 2018; 379(16):1509-18.

4. McNeil JJ, Nelson MR, Woods RL, et al. N Engl J Med. 2018; 379(16):1519-28.

5. Guirguis-Blake JM, Evans CV, Senger CA, et al. Ann Intern Med. 2016; 164(12):804-13.

6. Whitlock EP, Burda BU, Williams SB, et al. Ann Intern Med. 2016; 164(12):826-35.

7. Zheng SL, Roddick AJ. JAMA 2019;321(3):277-287.

8. Bibbins-Domingo K. Ann Intern Med. 2016;164(12):836-45.

9. Bell AD, Roussin A, Cartier R, et al. Can J Cardiol. 2011; 27(3):S1-59.

10. Piepoli MF, Hoes AW, Agewall S, et al. Euro Heart J. 2016; 37(29):2315-81.

11. Kolber, MR. and Korownyk, C. Exp Opinion Pharm. 2014; 15(2):153-7.

12. Williams CD, Chan AT, Elman MR, et al. Am J Prev Med. 2015;48(5):501-8.

13. Antithrombotic Trialists' (ATT) Collaboration. Lancet 2009; 373: 1849-60

Authors do not have any conflicts of interest to declare.