Drug Profile

Aspirin belongs to a family of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). It often is used to treat arthritis in older adults. Aspirin also is prescribed as a preventive medicine for illnesses such as heart disease. The Food and Drug Administration (FDA) has approved the use of aspirin for patients who have had a previous heart attack or unstable chest pain (angina) to reduce the risk of death and nonfatal heart attacks; patients with chronic stable angina to reduce the risk of heart attacks and sudden death; patients who have undergone revascularization procedures, such as the placement of a stent for a preexisting condition; patients with a suspected acute heart attack to reduce vascular mortality; and patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli (clots) to reduce the incidence of death and nonfatal stroke.

The use of aspirin in the aforementioned situations is known as secondary prevention because the patient already has a preexisting cardiovascular condition.

The U.S. Preventive Services Task Force (USPSTF) — a volunteer panel of national experts in evidence-based medicine and disease prevention that works independently of industry influences — in 2022 issued updated recommendations on the regular use of aspirin for primary prevention of cardiovascular events (especially heart attack and stroke) in patients without preexisting cardiovascular disease.[1] The USPSTF determined that for individuals aged 40 to 59 years, only those with 10% or greater 10-year cardiovascular disease risk have a small net benefit with the initiation of regular low-dose aspirin use for primary cardiovascular disease prevention (moderate-certainty evidence). Consequently, the USPSTF recommended that the decision to initiate low-dose aspirin use for primary prevention of cardiovascular disease in this group should be an individual one. This means that, after consultation with a clinician, individuals in this group who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin for the primary prevention of cardiovascular disease. On the other hand, those who place a higher value on avoiding the potential harms or the burden of taking a daily preventive medication may opt not to initiate low-dose aspirin use for the primary prevention of cardiovascular disease. The USPSTF noted that individuals in this group who are not at increased risk of bleeding and are willing to take low-dose aspirin daily are more likely to benefit.

The USPSTF also determined that initiating low-dose aspirin use in individuals aged 60 years or older has no net benefit for the primary prevention of cardiovascular disease (moderate-certainty evidence).[1] Therefore, it recommended against initiating low-dose aspirin use in adults aged 60 years or older for this purpose. There are several forms of aspirin available: plain aspirin, enteric-coated aspirin and buffered aspirin. In previous editions of Worst Pills, Best Pills News, we recommended the use of enteric-coated aspirin over plain or buffered aspirin because enteric coating was once thought to reduce the overall risk of bleeding in the gastrointestinal (GI) tract, as this form of aspirin does not dissolve in the stomach. The weight of the evidence now indicates that the risk of GI bleeding is similar among plain, enteric-coated and buffered aspirin.[2],[3],[4],[5] This is probably at least partially due to the fact that, once aspirin is absorbed into the blood, it can cause GI bleeding not related to local irritation but due to its effects on diminishing the natural protection of the GI tract and blood clotting.

We have listed buffered aspirin (ASCRIPTIN, BUFFERIN) as a Do Not Use drug because it is no better than plain aspirin and is more costly.

Adverse effects

NSAIDs can cause serious harm, including death, from bleeding in the stomach or intestines. Bleeding can occur at any time and without warning, and older people are more likely to experience adverse effects from bleeding. Combining aspirin with the antiplatelet drug clopidogrel (PLAVIX) further increases the risk of gastrointestinal bleeding.[6] Aspirin use also increases the risk of bleeding between the skull and the outside of the brain (subdural hematoma), although the absolute increase in risk is very low.[7]

Older adults are also more likely to have reduced liver and kidney function. Some doctors believe people over age 70 should be started on half the usual dose of aspirin.[8]

Interactions

A 2013 study published in Circulation, the journal of the American Heart Association, found that patients with atrial fibrillation who were receiving oral anticoagulants (blood thinners for preventing blood clots) as well as aspirin had an increased risk of bleeding compared with patients who were receiving only oral anticoagulant therapy with no aspirin.[9]

A study published in JAMA Internal Medicine in 2014 showed that the risk of major bleeding in patients with venous thromboembolism (VTE; blood clots in large veins that can break off and travel to the lung) using anticoagulants increased significantly when the patient also took NSAIDs or aspirin.[10]

Studies show...

One meta-analysis (a study that combines data from many other studies) examined the risks and benefits of adding aspirin therapy to the drug regimen of patients who were already taking an oral anticoagulant such as warfarin (COUMADIN), including patients with atrial fibrillation or with mechanical heart valves. This study demonstrated that there is little support in the published literature for the common clinical practice of adding aspirin to oral anticoagulant therapy except in select patients with a mechanical heart valve. The additional risk of bleeding was not thought to be warranted.[11]

Another study examined the effects of long-term, low-dose aspirin therapy in preventing VTE in healthy women. The study found that aspirin therapy is not effective in primary prevention of VTE in women with low-to-moderate risk of VTE.[12]

According to a study in the Annals of Internal Medicine, taking 75 to 81 milligrams of aspirin a day (one low-dose aspirin tablet) could be the safest, most effective way to prevent heart disease in patients who require aspirin therapy.

The study also found that taking doses of aspirin larger than 100 milligrams a day does not have any clear benefit for preventing heart disease — and it may actually be harmful to patients' health.[13]

Patients who frequently use medication to relieve headache pain may develop a condition known as medication overuse headache (MOH). According to a 2004 review published in the medical journal Lancet Neurology,[14] there is substantial evidence that all headache drugs can cause MOH in patients who use these drugs excessively.

The March 2013 issue of Worst Pills, Best Pills News discussed two studies dealing with MOH. In the first study, the treatment for MOH was simple: basic information tailored to the individual patient, including a discussion with the patient's doctor of both the role of drugs in developing MOH and the likelihood that stopping painkiller overuse would lead to an improvement. The second study involved a review of MOH treatment guidelines, including evidence concerning the manner in which the previously overused painkillers were discontinued.

Based on the results of both studies, patients should discuss with their doctors the important details of MOH and, depending on their individual case, the type of withdrawal from the MOH-causing drugs that is best for them.[15]

Results of a major government-funded clinical trial, called ASPREE, published in the New England Journal of Medicine (NEJM) in 2018, demonstrated that long-term daily use of low-dose aspirin in elderly adults who did not have cardiovascular disease, dementia or physical disability did not decrease the risk of heart attack, stroke or other serious cardiovascular disease. However, it did increase the risk of major bleeding.[16],[17],[18]

Results of another major study, called ASCEND, also published in the NEJM in 2018, showed that daily aspirin use in diabetic patients who had never had cardiovascular disease led to a lower risk of serious heart disease, but this benefit was offset by an increased risk of major bleeding.[19]

A third major study, called ARRIVE, published in Lancet in 2018, studied long-term daily use of low-dose aspirin in adults (average age 64 years) without prior cardiovascular disease or diabetes who had low 10-year risk of developing cardiovascular disease, although the researchers had aimed to enroll subjects with moderate risk.[20] After a median of five years of follow-up, the two groups had similar rates of adverse cardiovascular events, but 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.

In 2021 The New England Journal of Medicine published results of a new trial called ADAPTABLE that showed that, in patients with a high risk of cardiovascular disease, daily low-dose aspirin was equally effective as higher-dose aspirin for preventing strokes, heart attacks and deaths from cardiovascular disease.

In 2023, Drug and Therapeutics Bulletin published an article on a sub-study of the ASPREE trial called the ASPREE-FRACTURE trial. This sub-study showed that there was no decrease in the risk of fractures, but there was an increase in the risk of serious falls when aspirin was taken at a dose of 100 mg daily for five years.[21]

In 2023 JAMA Network Open published an article on a new analysis of the data from the ASPREE trial showing that healthy older adults who used low-dose aspirin did not have a lower rate of heart disease but did have an increased risk of major bleeding.[22]

In 2024 The American Journal of Health-System Pharmacy published an article showing that using an oral anticoagulant in combination with aspirin can increase the risk of any type of bleeding.[23]

Regulatory actions surrounding aspirin

2003: Bayer, the manufacturer of Genuine Bayer Aspirin, petitioned the FDA to allow the use of aspirin to reduce the risk of a first heart attack in patients with a coronary heart disease risk of 10% or greater over 10 years. This is known as primary prevention.

On Dec. 8, 2003, the FDA's Cardio-Renal Drugs Advisory Committee met to evaluate the results of five published clinical trials[24],[25],[26],[27],[28] submitted by Bayer to support their petition. The committee refused to recommend aspirin for primary prevention. The following were the official concerns of the FDA:

In only one[28] of the five studies submitted by Bayer was there a reduction in fatal heart attacks. In this study, there was a larger, though not statistically significant, increase in fatal sudden death, strokes or other fatal cardiovascular events.

The lack of efficacy (prevention of cardiovascular events, primarily a first heart attack) in the face of associated morbidity (i.e., bleeding) prevents the recommendation of use of aspirin for the primary prevention of cardiovascular morbidity and mortality.[29]

2020: The FDA and Health Canada (an agency in Canada similar to the FDA) warned that use of NSAIDs at about 20 weeks or later in pregnancy causes rare but serious kidney problems in the fetus.[30],[31] These kidney problems can lead to oligohydramnios, a condition in which there are low levels of amniotic fluid surrounding the baby. Amniotic fluid normally provides a protective cushion and plays an important role in the development of a baby's lungs, digestive system and muscles. Oligohydramnios, in turn, can lead to decreased range of motion in a baby's arms and legs and delayed lung maturation.