The Future of Aspirin in Primary CVD Prevention

Veronica Hackethal, MD

What exactly is the role of aspirin in CVD prevention? Two notable studies from ESC 2018 and 3 ongoing studies sought to address that very question. 

The Future of Aspirin in Primary CVD Prevention: Results from ESC 2018 and Ongoing Trials. While aspirin's (ASA) role in cardiovascular disease (CVD) prevention has been established since the 1980s, many studies are still trying to fully address a persistent question: What role should aspirin have in cardiovascular disease prevention? Two notable studies presented in August at the European Society of Cardiology Congress 2018 sought more data to help answer the question. What did they find? And what issues do ongoing trials hope to clarify? Scroll through the quick slideshow above to get all the details.

Aspirin's Role in CVD Prevention. What role should ASA have in primary CVD prevention? Four outgoing trials seek to answer that very question, 2 of the studies with populations that have not been previously studied. 

ARRIVE Presented at ESC 2018.3 ARRIVE, a randomized, double-blind, placebo-controlled trial, is the first primary prevention trial in moderate CVD risk and included 12 546 patients aged ≥55 years (men) and ≥60 years (women). Patients were randomized to once-daily 100 mg ASA or placebo with the primary endpoint being a composite of first CV death, MI, unstable angina, stroke, or TIA. 

Risks of ASA Outweigh Benefits in Low CVD Risk.3 No significant difference in primary endpoint for ASA vs placebo: HR 0.96, 95% CI 0.81–1.13, p=0.6038. Risk of GI bleeding over 2 times higher with ASA vs placebo HR 2.11; 95% CI 1.36–3.28; p=0.0007. Results support evidence suggesting risks of ASA outweigh benefits in low CVD risk. The population was also more representative of low CVD risk. 

ASCEND Presented at ESC 2018.4 ASCEND, a RCT of 15 480 adults in the UK with diabetes and no known CVD randomized patients to once daily 100 mg ASA or placebo. The primary endpoint was the first serious vascular event (MI, stroke, TIA, death from vascular cause, excluding intracranial hemorrhage). 

No Added Overall Benefit of ASA.4 Risk of serious vascular events 12% lower with ASA vs placebo:  RR 0.88; 95% CI 0.79 to 0.97; P=0.01. Risk of major bleeding 29% higher with ASA vs placebo: RR 1.29; 95% CI, 1.09 to 1.52; P=0.003. Absolute benefits of ASA were counterbalanced by bleeding and there was no added overall benefit of ASA. 

Ongoing Primary Prevention Trials. ASPREE, the largest primary prevention trial in elderly without known CVD, is a double-blind, randomized placebo-controlled study with 19 114 participants in the US and Australia. Patients were randomized to daily 100 mg ASA or placebo for 5 years.5 ACCEPT-D is an open-label trial in Italy with a planned enrollment of 5170 participants aged ≥50 years with T1DM/T2DM and CVD on statins. Participants were randomized to ASA and simvastatin or simvastatin alone with a primary combined endpoint including CVD death, nonfatal MI, nonfatal stroke, and CV hospitalization.6

Ongoing Primary Prevention Trials. CARING, an open label, randomized, parallel-arm study with a planned enrollment of 3200 participants aged ≥50 years with T2DM or impaired fasting glucose. Participants were randomized to low-dose ASA upon awakening or bedtime. Primary outcomes include circadian effects of ASA on primary prevention of CV, cerebrovascular, fatal renal, and non-fatal CV events in those with T2DM/impaired fasting glucose.7 

Take Home Points:

  • Unclear if ASA should be used in low-moderate CVD risk
  • ARRIVE found risks of ASA outweigh benefits in low CVD risk
  • ARRIVE aimed to assess moderate CVD risk but population represented low CVD risk, leaving role of ASA in moderate CVD risk unclear
  • ASCEND found no added overall benefit of ASA in diabetes and no known CVD
  • Ongoing trials include ASPREE, ACCEPT-D, and CARING
  • Whether to use ASA in primary prevention may continue to be individual decision, based on risk vs benefit preferences

References: 

1. Steering Committee of the Physicians' Health Study Research Group. Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med. 1989;321:129-135.
2. USPSTF.  Final recommendation statement: Aspirin use to prevent cardiovascular disease and colorectal cancer: Preventive medication. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer. Published 2016. Accessed September, 13 2018.
3. 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.
4. ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018.
5. ASPREE. Scientific overview.  Accessed September, 13 2018 at: https://aspree.org/usa/researchers/aspree-scientific-summary/. 
6. De Berardis G, Sacco M, Evangelista V, et al. Aspirin and simvastatin combination for cardiovascular events prevention trial in diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. Trials. 2007;8:21.
7. Chronotherapy with low-dose aspirin for primary prevention of cardiovascular events in subjects with impaired fasting glucose or diabetes (CARING study). Accessed September, 13 2018 at: https://clinicaltrials.gov/ct2/show/nct00725127?term=chronotherapy+with+low-dose+aspirin+for+primary+prevention+%28caring%29&rank=1

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