Daily Low-Dose Aspirin Should Not Be Used to Prevent a First Heart Attack or Stroke

Cardiovascular disease — including coronary heart disease (angina [chest pain due to inadequate blood flow to the heart] or heart attack), ischemic stroke (caused by blockage with a blood clot in a brain artery) and peripheral vascular disease (obstruction of a large blood vessel in the arms or legs) — is the leading cause of death worldwide.[1]

The most important way to prevent cardiovascular disease is by maintaining a healthy lifestyle (through a balanced diet, regular exercise and avoiding smoking) and by adequately treating diabetes, high blood pressure and high cholesterol.

Because of its ability to inhibit platelets and thus prevent clots from forming, low-dose aspirin (BAYER ASPIRIN, ECOTRIN) in doses that range from 75 to 100 milligrams (mg), often called “baby aspirin,” was once routinely advocated for use in healthy adults age 40 and older to prevent heart attacks, strokes and death. However, support for this blanket recommendation has eroded in recent years because long-term use of aspirin, even in low doses, has been shown to increase the risk of internal bleeding. Although such bleeding is rarely fatal, it can lead to serious illnesses and hospitalizations.[2]

Currently, there is clear evidence that use of low-dose aspirin is effective in reducing the risk of a subsequent heart attack or stroke and the risk of death in patients who have already had a heart attack or stroke or who have other evidence of cardiovascular disease (such as angina) or a history of a coronary artery bypass operation or other procedure (such as placement of a stent [a small metal tube]) to treat a blockage in a coronary artery.[3] Such aspirin use is called “secondary prevention.” For this use, the benefits of aspirin far outweigh its risk of major bleeding. The exceptions to this case are patients who are allergic to aspirin, those with increased bleeding risk (including ulcers in the stomach or small intestines) and those with bleeding disorders.

In contrast, there has been a consistent lack of convincing evidence that the benefits of aspirin outweigh its risks for preventing a heart attack, stroke or other cardiovascular event in healthy people with no prior history of cardiovascular disease, which is called “primary prevention.”[4],[5]

Citing such insufficient evidence, the Food and Drug Administration (FDA) in 2014 denied a petition submitted by Bayer, the first manufacturer of aspirin, that requested approval to market aspirin for primary prevention of a first heart attack in patients who had a high risk of developing cardiovascular disease (defined as having a 10% or greater risk of developing chronic heart disease within 10 years).[6]

Since the FDA’s rejection of Bayer’s petition, three randomized clinical trials (ARRIVE, ASCEND and ASPREE) and a related systematic review investigated the use of aspirin for primary prevention of cardiovascular disease.

Recent studies

The ARRIVE trial randomized over 12,500 subjects (average age 64 years) without prior cardiovascular disease or diabetes to receive either 100 mg of aspirin or a placebo daily.[7] The subjects had a low 10-year risk of developing cardiovascular disease, although the researchers had aimed to enroll subjects with moderate risk. After a median of five years of follow-up, the two groups had similar rates of a composite (combined) outcome that included cardiovascular death, heart attack, unstable angina, stroke or transient ischemic attack (brief episode of stroke-like symptoms). However, 1% of the aspirin group subjects experienced gastrointestinal bleeding compared with only 0.5% of the placebo group subjects, a difference that was statistically significant.

The ASCEND trial randomized nearly 15,500 adults (average age 63 years) with diabetes who did not have cardiovascular disease to receive either 100 mg of aspirin or a placebo daily.[8] After an average of seven years of follow-up, a slightly lower percentage of the aspirin group subjects had experienced serious cardiovascular events (defined as heart attack, stroke or transient ischemic attack, or death from any vascular cause other than brain hemorrhage) than the placebo group subjects (8.5% versus 9.6%, respectively). But this small cardiovascular benefit was offset by a significantly increased risk of major bleeding in the aspirin group subjects.

The ASPREE trial randomized more than 19,100 healthy adults aged 70 or older to receive either 100 mg of aspirin or a placebo daily.[9] After a median of five years of follow-up, the aspirin group subjects did not have a lower rate of cardiovascular disease (defined as fatal coronary heart disease, nonfatal heart attack, fatal or nonfatal stroke, or hospitalization for heart failure) but had a significantly higher major bleeding rate than did the placebo group subjects.

Finally, the systematic review, which was published online in Family Practice in November 2019 and included data from the above three trials and others, estimated that for every 1,200 adults who take aspirin for five years for primary prevention of cardiovascular disease, there will be four fewer major adverse cardiovascular events (defined as cardiovascular death, nonfatal heart attack or nonfatal stroke).[10] However, there also will be three more strokes caused by bleeding in the brain and eight more major bleeding events as a result of aspirin therapy. The review concluded that aspirin should not be recommended for primary prevention of cardiovascular disease.

Likewise, we believe that the collective recent evidence does not support such use of aspirin.

What You Can Do

To prevent cardiovascular disease, eat a balanced diet (one that is high in fruits, vegetables, nuts, whole grains, fish and lean vegetable or animal protein), exercise regularly and do not smoke.[11] Also, if you have diabetes, high blood pressure or high cholesterol, make sure these conditions are being appropriately controlled.

Only if you have had a heart attack, stroke or other cardiovascular event or have a history of a coronary artery surgery or stent procedure should you be taking low-dose aspirin daily to prevent a heart attack or stroke unless you are allergic to aspirin or are at high risk of bleeding.

Otherwise, if you do not have cardiovascular disease, you should not take aspirin to prevent a first heart attack, stroke or other cardiovascular event, particularly if you are over the age of 60, because the benefits of such treatment generally do not exceed its bleeding risk. If your doctor has prescribed aspirin for you and you have never had a cardiovascular event before, discuss this article with him or her. Do not initiate or discontinue daily aspirin without discussing this with your doctor.
 

References

[1] American Heart Association. Nearly half of all U.S. adults have some form of cardiovascular disease. January 31, 2019. https://newsroom.heart.org/news/nearly-half-of-all-u-s-adults-have-some-form-of-cardiovascular-disease. Accessed April 28, 2020.

[2] Peters AT, Mutharasan RK. Aspirin for prevention of cardiovascular disease. JAMA. 2020;323(7):676.

[3] Food and Drug Administration. Use of aspirin for primary prevention of heart attack and stroke. May 2, 2014. https://www.fda.gov/drugs/drug-information-consumers/use-aspirin-primary-prevention-heart-attack-and-stroke. Accessed April 28, 2020.

[4] Ibid.

[5] Moriarty F, Ebell MH. A comparison of contemporary versus older studies of aspirin for primary prevention. Fam Pr. November 21, 2019. doi: 10.1093/fampra/cmz080. [published online ahead of print]

[6] Food and Drug Administration. Citizen petition denial response from FDA to Bayer Healthcare LLC. May 2, 2014. www.regulations.gov/#!documentDetail;D=FDA-1977-N-0018-0101. Accessed April 28, 2020.

[7] 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(10152):1036-1046.

[8] ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379(16):1529-1539.

[9] McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379(16):1509-1518.

[10] Moriarty F, Ebell MH. A comparison of contemporary versus older studies of aspirin for primary prevention. Fam Pr. November 21, 2019. doi: 10.1093/fampra/cmz080. [Published online ahead of print].

[11] Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646.