The following are key points to remember from this editorial about the US Preventive Services Task Force (USPSTF) report on aspirin for primary prevention:

1. Aspirin therapy is not a one-size-fits-all therapy. It may offer benefit for some patients, while the risk–benefit ratio may not be favorable for others.
2. Early trials of aspirin use in primary prevention initially showed benefit for large populations of patients. This includes a reduction in myocardial infarction risk in the Physicians’ Health Study. Subsequent studies, including the Women’s Health Study, found no reduction in major cardiovascular disease (CVD) with primary prevention aspirin use. However, there was a reduction in stroke risk in the Women’s Health Study.
3. Early trials of primary prevention aspirin use did find small absolute increases in major bleeding risk.
4. Several guidelines and guidance documents, including the 2016 USPSTF, recommended use of primary prevention aspirin for patients aged 50-59 years at elevated CVD risk without bleeding (Grade B). The 2016 USPSTF recommended individual decision making for patients aged 60-69 years at elevated cardiovascular risk and no bleeding (Grade C) and made no recommendation for patients aged <50 or >69 years due to lack of evidence.
5. Over the past 30 years, large cardiovascular preventative efforts have greatly impacted public health. These include increasing use of statin medications and antihypertensive medications along with reductions in tobacco use.
6. In 2018, three key trials of primary prevention with aspirin were published. First, the ASPREE trial found that among healthy older patients (aged ≥65 years), use of low-dose daily aspirin was associated with increased risk for mortality (5.9% vs. 5.2% for placebo at median 4.7 years) and cancer mortality (3.1% vs. 2.3%). There were similar rates of major bleeding (0.3% in both groups). Second, the ASCEND trial in patients with diabetes found that use of daily low-dose aspirin reduced the risk of CVD events (8.5% vs. 9.6%, mean 7.4 years of follow-up) but was offset by increased major bleeding risk (4.1% vs. 3.2%). Third, the ARRIVE trial of middle-aged and older adults at intermediate risk for atherosclerotic cardiovascular disease (ASCVD) without diabetes found a nonsignificant reduction in ASCVD events (4.29% vs. 4.48%, median 5 years of follow-up) but a doubling of gastrointestinal bleeding (0.97% vs. 0.46%).
7. In reviewing the three key trials published in 2018, the rates of antihypertensive and statin medications were quite high, while tobacco use was relatively low. As such, there may be less opportunity for primary prevention aspirin to demonstrate benefit given better risk factor control.
8. In the more recent TIPS-3 trial (2020), patients at elevated risk for ASCVD were randomized to receive aspirin or placebo in addition to a polypill containing statin and antihypertensive medications. There was low baseline use of these two medications. This trial found a significant reduction in CVD events (4.1% vs. 5.8% over mean 4.6 years) among patients randomized to receive aspirin.
9. In 2019, the American College of Cardiology (ACC)/American Heart Association (AHA)/multispecialty guidelines recommended that aspirin was a class III (harm) medication for primary prevention in patients aged ≥70 years. They also reduced the recommendation strength (class IIb) for use in patients aged 40-70 years with a focus on individual decision making.
10. The 2021-2022 USPSTF recommendation changed its recommendation for primary prevention aspirin use. Specifically, it recommends individual decision making for patients aged 40-59 years at increased risk of CVD and discourages use for patients aged ≥60 years.

Clinical Topics: Dyslipidemia, Geriatric Cardiology, Prevention, Nonstatins, Novel Agents, Statins

Keywords: Antihypertensive Agents, Aspirin, Atherosclerosis, Cardiovascular Diseases, Diabetes Mellitus, Gastrointestinal Hemorrhage, Geriatrics, Heart Disease Risk Factors, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocardial Infarction, Neoplasms, Primary Prevention, Public Health, Risk Assessment, Risk Factors, Stroke, Tobacco Use

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