Making Sense of it all: A Review of Recent Studies on the Role of Aspirin in Preventing Heart Disease and how ADAPTABLE fits in the Picture

Aspirin is a drug that has been used for decades to prevent the occurrence of a heart attack or stroke by thinning blood so clots do not form. Doctors recommend either high-dose (325 mg) or low-dose (81 mg) aspirin and its use across the United States is fairly balanced between high-dose and low-dose aspirin.

The ADAPTABLE study aims to provide patients and doctors with information on the best dose of aspirin to prevent another heart attack or stroke in people living with heart disease. Doctors refer to this as secondary prevention. Recently, four major studies contributed to our understanding of aspirin’s role in preventing a heart attack or stroke for individuals who do not have known cardiovascular disease and have not experienced a heart attack or stroke. Doctors refer to this as primary prevention. Working with ADAPTABLE patient partner, Greg Merritt, we provide a summary of the results for each of these studies below.

Schuyler Jones, MD

“We all deeply believe in the work required to finish the ADAPTABLE study, and we’re excited to maintain momentum over the fall and winter months. Please take a look of our thoughts on the recent aspirin studies and their applicability to ADAPTABLE.”

The ASCEND Trial: Aspirin in Primary Prevention of Vascular Events in Patients with Diabetes

The ASCEND study included patients with diabetes, a major risk factor for developing heart disease and stroke, but without known heart disease. In this study, approximately half of the 15,480 patients took a low-dose (100 mg daily) of aspirin, and the other half took a placebo pill. A placebo is a substance that does not contain an active drug.

After an average of 7.4 years, patients who took aspirin experienced 11 percent fewer cardiovascular problems, including heart attacks, strokes or mini-strokes, and even death due to a cardiovascular cause. This benefit was stronger in patients weighing 70 kg (154 lbs) or more. Researchers estimated one cardiovascular problem was prevented for every 91 patients who took aspirin. Since aspirin is a blood-thinner, it is also associated with more bleeding problems. For every 112 patients who took aspirin, one more bleeding event occurred compared to patients who did not take aspirin. The increase in bleeding events did not lead to death or a stroke.

The ARRIVE Trial: Aspirin in Primary Prevention in Non-Diabetic Patients at Moderate-Risk of Cardiovascular Diseases

The ARRIVE study was similar to the ASCEND trial (by including patients without known heart disease) but did not include patients with diabetes. This study included patients with a moderate risk for developing heart disease based on factors such as high blood pressure, smoking, or high blood levels of cholesterol. Half of the 12,546 patients took 100 mg of aspirin each day, but this time, aspirin did not prevent cardiovascular problems when compared to a placebo pill. After an average of 5 years, whether or not they took aspirin, approximately 4 percent of all patients experienced either a heart attack, stroke or mini-stroke, unstable chest pain, or death due to a cardiovascular cause. Although bleeding from the stomach or intestines was rare and occurred in less than 1 percent of the patients in both groups, patients who took aspirin were more likely to experience this type of bleeding.

Greg Merritt

“It continues to be an honor and privilege to be a patient partner in the ADAPTABLE Study.As a patient, I often see a wealth of information in the media about the role of aspirin in preventing or treating heart disease. However, my friends, fellow heart patients, and I are often confused by this influx of information. I love having ‘experts that I trust’ put into context these reports. Putting results from these studies in a language lay people can understand helps a great deal, so we don’t spread information that has not been scientifically proven.”

The ASPREE Trial: Aspirin in Primary Prevention of Dementia or Disability

The ASPREE study also included exclusively patients with no previous heart disease or stroke, but only if they were considered healthy and at least 65 to 70 years old. Half of the 19,114 participants took 100 mg of aspirin each day, and the other half took a placebo. After an average of almost 5 years, the study did not show benefits of aspirin in preventing death, dementia, or chronic physical disability, but the risks of major bleeding problems increased. In addition, aspirin did not prevent heart attacks, strokes, and other cardiovascular events. The ASPREE study raises concern for a potentially higher risk of death with aspirin in elderly patients without previous heart disease or stroke. The study found a higher rate of cancer deaths in the participants who took aspirin. This finding should be interpreted with caution because it was not the main focus of the study, and most importantly because previous studies demonstrated the opposite: a protective effect of aspirin on death related to cancer.

Meta-Analysis on the Interaction between Aspirin Dose and Body Weight

The fourth study was a meta-analysis, which combines and evaluates the results from multiple studies. This analysis looked at the results from nine studies involving nearly 103,000 patients (but did not include any of the results from the three studies above). The purpose of the analysis was to decide if aspirin dosing should be different for heavier people compared to people with lower body weights. The authors found that only patients weighing less than 70 kg (154 lbs) benefited from a daily dose of aspirin of 70-100 mg. This benefit (prevention of a heart attack or stroke) decreases as the weight of the patient increases. Patients weighing 70 kg or more benefited from daily doses of aspirin greater than or equal to 300 mg. Patients with lower body weights did not benefit from this higher dose of aspirin in general. Of note, these nine studies did not set out to research an association between body weight and aspirin dose, so results from this analysis should be interpreted with caution.

Although aspirin can prevent cardiovascular events in some patients, these studies show that it comes at a cost in terms of risk of bleeding. Some patients might fear heart attacks and strokes more than bleeding, but some patients might worry more about bleeding. The choice to use aspirin or not must be a joint decision made by a patient and their doctor, using scientific information as well as personal preferences. 

 

 Take-home Messages

  •  In diabetic people without cardiovascular disease, the overall benefits of aspirin is low to moderate.
  • In people at moderate risk of developing a cardiovascular disease, but without diabetes, aspirin doesn’t seem to protect people from a first cardiovascular problem.
  • In people at least 65 to 70 years old without cardiovascular disease, aspirin does not protect against death, dementia, or persistent disability, and neither does it protect from heart attacks or strokes, but it increases the risk of bleeding.
  • The effectiveness of low-dose (70-100 mg) and high-dose aspirin (at least 300 mg) to prevent cardiovascular complications has not been researched in a study specifically designed for this purpose, particularly in patients who have experienced previous heart attacks or strokes. It is expected that benefits of aspirin are higher for this group versus patients who have not experienced these events.
  • A relationship between weight and aspirin dose may exist, but a future study designed specifically to research this association is needed.
  • ADAPTABLE is the largest study comparing two doses of aspirin in patients who have cardiovascular disease. This is a different population than the recent studies, which was comprised of study participants with no known heart disease.
  • The benefit of aspirin to prevent future events in people who have heart disease is established, but the optimal dose is not known. Results from ADAPTABLE will provide information to help doctors and patients answer this question.
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