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Will an aspirin a day keep MI away? New evidence, recommendations from the ACC/AHA
New guideline gives aspirin a downgrade.
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The use of aspirin for primary prevention became a hot topic after the publication of three landmark trials in 2018, which clarified the role of low-dose aspirin in primary CVD prevention. Although the European CVD prevention guidelines have drawn a line in the sand — not recommending aspirin in patients without CVD since 2016 — the U.S. guidelines have historically recommended use of aspirin based on CVD risk assessment. However, with the new publication of the 2019 American College of Cardiology/American Heart Association Guidelines on Primary Prevention of Cardiovascular Disease, simultaneously published and presented at the ACC Scientific Session in March, did the U.S. decide to follow the more stringent recommendations of the European guidelines?
The 2019 ACC/AHA guideline downgraded the recommendation for primary prevention with aspirin, instead supporting healthy life choices, such as tobacco cessation, physical activity and weight management. See Table 1 for comparison with other U.S. guidelines. In addition, the guideline supports prior U.S. recommendations pertaining to lipid, BP and glucose control, while promoting a recipe for more patient and physician shared decision-making.
Although the guidelines recommend frequent calculation of the 10-year atherosclerotic CVD risk using the Pooled Cohort Equations for adults aged 40 to 75 years, probably the greatest change in recommendations is to forgo the use of that result to create cut points or a risk threshold to determine whether or not aspirin is recommended. Instead, the guideline favors a more practical approach, providing a list of risk-enhancing factors (Table 2) to be used with the ASCVD risk assessment for guiding practitioners on the use of aspirin for primary prevention as well as giving the option of performing a coronary artery calcium scan. This strategy allows more patient individualization, including evaluation of risk factors such as family history of premature MI, poor lipid/glucose control, or elevation in CAC score. Physicians are empowered to tailor aspirin utilization based on individual patient and clinician preferences as well as bleeding risk.
Trials change thinking
Three landmark trials evaluating aspirin 100 mg per day vs. placebo in more than 47,000 patients followed for about 5 to 8 years set the tone for the major change in primary CVD prevention. In the ASPREE trial (n = 19,114; mean ASCVD risk not reported), patients aged 70 years or older (65 years or older if African-American or Hispanic-American) did no better on aspirin than placebo from a disability-free or CV event-free survival perspective; however, major hemorrhage occurred significantly more often in aspirin-treated participants than placebo-treated participants (8.6 per 1,000 person-years vs. 6.2 per 1,000 person-years; HR = 1.38; 95% CI, 1.18-1.62). The most frequent hemorrhagic events in the aspirin group were any intracranial bleeding (2.5 per 1,000 person-years) and any gastrointestinal (GI) bleeding (3.8 per 1,000 person-years).
In contrast, in the ASCEND trial (n = 15,480; 17% with 5-year vascular risk of 10% or more), patients with diabetes and free of CVD had an RR reduction in the primary outcome of vascular death, nonfatal MI, nonfatal stroke or transient ischemic attack of 12% with low-dose aspirin vs. placebo, with an increased RR of major bleeding by 29% (driven primarily by GI bleeding). The number needed to treat for patients with diabetes with no CV risk was 91 to prevent one composite vascular event over 7 years, whereas the number needed to harm was 112 for one major bleeding event in the same time period.
The ARRIVE trial (n = 12,546; mean 10-year ASCVD risk of 17%) assessed patients with intermediate CV risk. Again, this trial demonstrated no difference in major CV outcomes and a twofold increased risk for GI bleeding (0.97% vs. 0.46%; HR = 2.11; 95% CI, 1.36-3.28). In the per-protocol analysis, aspirin significantly reduced the risk for MI by 47%.
Most recently, a meta-analysis published in JAMA in January analyzed 13 trials of 164,225 participants who had no CVD and a follow-up of at least 12 months, including the three aforementioned studies. The primary CV outcome of the composite of CV mortality, nonfatal MI and nonfatal stroke was significantly reduced with aspirin compared with no aspirin with a number needed to treat of 265. However, aspirin use was associated with significantly increased risk for major bleeding with a number needed to harm of 210. When studies were analyzed grouped by low and high ASCVD risk, both groups showed a reduced primary CV outcome with increased major bleeding risk.
Niche usage
With the literature showing overall little benefit in comparison to the risk for major bleeding, the ACC/AHA gave an overall lower recommendation for aspirin but was still compelled to give consideration to a niche that might benefit from aspirin focusing in on adults aged 40 to 70 years without bleeding risk (recommendation class IIb). No recommendations for patients younger than 40 years were made due to insufficient evidence. The authors stressed that aspirin use could be tailored after discussion with the patient about their values for MI prevention vs. risk for serious bleeding and the ability to control other CVD risk factors. It was emphasized that there was no data supporting the use of aspirin doses higher than 100 mg compared with lower doses.
Additional recommendations include a class III (harm) for use of aspirin for primary CVD prevention in patients older than 70 years and patients of any age at high risk for bleeding (ie, history of prior GI bleeding, peptic ulcer disease, history of prior bleeding from other sites, age older than 70 years, thrombocytopenia, coagulopathy, chronic kidney disease, and medications that increase bleeding risk such as NSAIDs, corticosteroids and anticoagulants).
So, will these new guidelines be adopted? Patients themselves have strong beliefs on whether or not aspirin use is worth the risk. It is up to clinicians to explore both the benefits and risks with each patient. For patients with well-controlled ASCVD risk and no risk-enhancing factors, negative CAC score and no bleeding risk, the answer would seem to be aspirin use is not worth the risk.
- References:
- Arnett DK, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.03.009.
- ASCEND Study Collaborative Group. N Engl J Med. 2018;doi:10.1056/nejmoa1804988.
- Bibbins-Domingo K, et al. Ann Intern Med. 2016;doi:10.7326/M16-0577.
- Fox CS, et al. Circulation. 2015;doi:10.1161/CIR.0000000000000230.
- Gaziano JM, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)31924-X.
- Mahmoud AN, et al. Eur Heart J. 2019;doi:10.1093/eurheartj/ehy813.
- McNeil JJ, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1805819.
- McNeil JJ, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1800722.
- Piepoli MF, et al. Eur J Prev Cardiol. 2016;doi:10.1177/2047487316653709.
- Zheng SL, et al. JAMA. 2019;doi:10.1001/jama.2018.20578.
- For more information:
- Claudia Lopez, PharmD, BCPS, is pharmacy operations manager, Memorial Hospital West, Pembroke Pines, Florida.
- Leo F. Buckley III, PharmD, BCCP, is senior pharmacist in the department of pharmacy services at Brigham and Women’s Hospital.
- Ahmed Aldemerdash, BS, PharmD, BCPS, is assistant professor and director of fellowship programs at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, and cardiovascular pharmacotherapy consultant and director of the PGY1 pharmacy residency program at King Saud University.
- Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS (AQ Cardiology), is the Cardiology Today Pharmacology Consult column editor. She is professor and chair of the department of pharmacy practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University. She can be reached at sspinler@binghamton.edu.
Disclosures: The authors report no relevant financial disclosures.