Low- and Regular-Dose Aspirin Equally Effective for Preventing Cardiovascular Disease, Trial Shows

The oral nonsteroidal anti-inflammatory drug aspirin can decrease the risk of blood clots by inhibiting platelets (clot-forming blood cells) and thereby reduce the risk of heart attack and other types of cardiovascular disease in certain patients. Mainly due to an increased bleeding risk, however, regular use of aspirin is not for everyone.

In the July 2020 issue of Worst Pills, Best Pills News, we discussed the current evidence supporting the benefits of long-term use of daily aspirin over its risks for the purpose of preventing a new cardiovascular event in patients with known atherosclerotic cardiovascular disease (such as those with a previous heart attack, stroke or other cardiovascular event or with a history of a coronary artery surgery or stent procedure) as long as they do not have an increased risk of bleeding.[1] This is called secondary prevention. In contrast, the benefits of daily aspirin use do not exceed the drug’s risks for preventing a first heart attack, stroke or other cardiovascular event (which is called primary prevention), particularly in individuals over the age of 60.

An important area of debate about long-term use of aspirin for secondary cardiovascular prevention is what aspirin dose best balances the drug’s benefits and risks.[2] Generally, two once-daily doses have been used: either adult (regular-dose) aspirin (300 to 325 milligrams [mg]) or low-dose (baby) aspirin (75 to 100 mg).

A new trial, called ADAPTABLE, provided a comparison of low- and regular-dose aspirin for secondary prevention of cardiovascular disease. Its findings were published in the May 27, 2021, issue of the New England Journal of Medicine.

The ADAPTABLE trial[3]

Funded by the Patient-Centered Outcomes Research Institute, a federally sponsored nonprofit organization, the ADAPTABLE trial was a large-scale yet relatively low-cost trial. Subjects for the trial were identified from electronic health records in 40 U.S. medical centers and in one health plan.

Overall, the trial researchers enrolled 15,076 subjects with preexisting atherosclerotic cardiovascular disease, defined as having any of the following: a prior heart attack; prior coronary revascularization procedure; confirmed 75% narrowing of one or more major coronary arteries; or history of chronic ischemic heart disease, coronary artery disease or other atherosclerotic cardiovascular disease. The median age of these subjects was 68 years, and 69% of them were men.

Using a web-based patient portal, the researchers randomly assigned subjects to take either 81-mg (low-dose) or 325-mg (regular-dose) aspirin daily. Subjects purchased their assigned aspirin dose over the counter. The researchers conducted all trial visits virtually or by telephone and ascertained patient outcomes remotely.

Overall, after a median of 26 months of trial follow-up, the researchers did not find significant differences between subjects in the two aspirin-dose groups with respect to the trial’s primary effectiveness endpoint (defined as the risk of death from any cause, hospitalization for heart attack or hospitalization for stroke) and primary safety endpoint (defined as hospitalization for major bleeding with an associated blood-product transfusion). Specifically, the primary effectiveness outcome occurred in 7.3% of low-dose aspirin subjects and 7.5% of regular-dose aspirin subjects. Similarly, the primary safety outcome occurred in 0.6% of subjects in each group.

A key weakness of this trial is that 42% of subjects assigned to the regular-dose aspirin group switched to low-dose aspirin shortly after randomization. These subjects likely switched because they or their doctors preferred the lower dose, given that about 85% of them had been taking low-dose aspirin before enrolling in the trial. In contrast, only 7% of subjects in the low-dose aspirin group switched to regular-dose aspirin after randomization. This imbalanced switching pattern is problematic because it could have led to underestimation of the true benefits and risks of the regular-dose aspirin.

Notwithstanding the limitations of the ADAPTABLE trial, its effectiveness finding is consistent with that from a frequently cited 2002 meta-analysis of evidence combined from multiple earlier randomized trials that was conducted by the Antithrombotic Trialists’ Collaboration. That meta-analysis found that daily low-dose (75-150 mg) aspirin was as effective as higher aspirin doses for long-term treatment for patients at high risk of serious cardiovascular events (nonfatal heart attack, nonfatal stroke or cardiovascular death).[4]

What You Can Do

If you and your doctor determine that you need to take aspirin daily for secondary prevention of cardiovascular disease, discuss this article with him or her to decide on the optimal aspirin dose for you.

Do not initiate routine aspirin use without consulting your doctor first, especially if you are already taking a blood thinner, because such use can increase your risk of bleeding and hospitalization compared with taking either drug alone. Likewise, do not discontinue routine aspirin use without medical supervision.
 

References

[1] Daily low-dose aspirin should not be used to prevent a first heart attack or stroke. Worst Pills, Best Pills News. July 2020. https://www.worstpills.org/newsletters/view/1344. Accessed September 7, 2021.

[2] Parker WAE, Storey RF. Aspirin dosing for atherosclerotic cardiovascular disease: should we be more ADAPTABLE? Cardiovasc Res. 2021;117(10):e123-e125.

[3] Jones WS, Mulder H, Wruck LM, et al. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med. 2021;384(21):1981-1990.

[4] Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7329):71-86.