Due to a number of recently published studies, the benefit/risk profile of therapy with daily aspirin for the primary prevention of myocardial infarction (MI) or stroke has come under increasing scrutiny. The consensus now seems to be that, while daily aspirin may lower the risk of heart attack, it isn’t right for everyone.
Researchers recently published a systematic review in the Journal of the American Medical Association in which they investigated the association of aspirin use for primary prevention with cardiovascular and bleeding events. Upon analysis of 13 randomized, clinical trials in over 164,000 subjects with no known history of cardiovascular disease, they found that—although regular aspirin use was associated with an 11% lower risk of MI and other cardiovascular events—such therapy may increase the risks of major bleeding episodes by nearly 50%. Researchers also found that roughly 1 in 200 people who were treated with aspirin would experience a major bleed. Aspirin had no effects on new cancer diagnoses or mortality.
"This study demonstrates that there is insufficient evidence to recommend routine aspirin use in the prevention of heart attacks, strokes and cardiovascular deaths in people without cardiovascular disease. There has been more uncertainty surrounding what should be done in patients who are at higher risk of cardiovascular disease and in patients with diabetes. This study shows that while cardiovascular events may be reduced in these patients, these benefits are matched by an increased risk of major bleeding events,” said lead author, Sean Zheng, BM, BCh, MA, MRCP, academic clinical fellow, Department of Cardiology, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom.
"Aspirin use requires discussion between the patient and their physician, with the knowledge that any small potential cardiovascular benefits are weighed up against the real risk of severe bleeding," he concluded.
In the ASCEND study that appeared in the New England Journal of Medicine, in the over 15,000 participants with diabetes who took daily aspirin (100 mg) or matching placebo for an average of 7.4 years, researchers found that for every 1,000 patients taking aspirin, 11 avoided MI, stroke, ministroke, or cardiovascular-related mortality. But, 9 of every 1,000 participants also had bleeding serious enough to cause hospitalization or death.
In the randomized, double-blind, placebo-controlled ARRIVE study recently published in Lancet, researchers assessed over 12,500 subjects with several cardiovascular risk factors—including high cholesterol or blood pressure, who took a daily aspirin (100 mg) or placebo to determine the safety and efficacy of aspirin use in subjects with moderate estimated risk of first cardiovascular event. Over 5 years, the incidence of MIs or related events were not lower in those taking regular aspirin. And while the incidence of gastrointestinal bleeding was low, it was twice as common in those taking regular aspirin vs those taking placebo.
Finally, in a fourth recent study published in the New England Journal of Medicine, researchers included over 19,000 older subjects aged 65 years and up who took regular aspirin (100 mg or more) or placebo daily for a median of 4.7 years, the risk of cardiovascular disease, dementia, and disability were not lower in those taking aspirin vs placebo. The risk of severe bleeding is those taking regular aspirin, however, was increased, which was consistent with the other studies.
In light of these results, let’s look at some of the pros and cons of daily therapy with aspirin:
The pros: The anticoagulative effects of aspirin therapy are what makes aspirin effective in preventing heart attacks and strokes. Patients who have previously had an MI or stroke could benefit, as can those with coronary artery stents, coronary artery bypass grafting, or angina.
Others who stand to benefit from daily aspirin therapy include those with diabetes and at least one other risk factor for (eg, smoking or high blood pressure), men older than 50 years, and women older than 60 years.
In addition, the US Preventive Services Task Force recommends daily aspirin therapy in those aged 50-59 years, those not at increased risk of bleeding, and those with an increased risk of heart attack or stroke of 10% or more over the next 10 years.
The US FDA, however, does not recommend daily aspirin therapy for preventing heart attack in individuals with no history of a heart attack, stroke, or other cardiovascular disease.
In patients who have had an MI or a coronary stent, aspirin therapy is essential, sometimes in combination with other anticoagulants. In these individuals, stopping daily aspirin therapy may have a rebound effect, and actually increase their risk of MI by triggering clot formation.
The cons: Daily aspirin therapy has several side effects, including:
- Increased risk of hemorrhagic stroke
- Gastrointestinal bleeding
- Allergic reaction
- Increased risk of stomach bleeds in those who also drink alcohol
Caution is also necessary in patients taking daily aspirin therapy who must undergo surgery or dental procedures due to a risk of excessive bleeding during surgery. The general consensus is that, in healthy adults taking aspirin regularly, alcohol intake should not exceed one drink per day for women of any age and in men older than 65 years, and up to two alcoholic beverages per day for men aged 65 years or younger.
Drug interactions are also a concern with concomitant daily aspirin use. Anticoagulants such as warfarin, apixaban, dabigatran, or rivaroxaban combined with aspirin can increase risks of major bleeding complications. Other drugs aspirin may interact with include the following:
- Ibuprofen taken regularly
- Some antidepressants, such as clomipramine and paroxetine
Supplements that regular aspirin use can interact badly with include:
- Cat’s claw
- Evening primrose oil
- Omega-3 fatty acids or fish oil
Ultimately, although daily aspirin therapy may be beneficial for secondary prevention of MI and stroke, as well as in patients with diabetes, it may not be beneficial for primary prevention in individuals without diabetes and in those aged 70 years and older, as it may actually increase the risk of major bleeding events.