Aspirin No Longer Preventative Drug for Cardiovascular Disease

Aspirin no longer preventative for CVD? Increased risk of hemorrhage with no significant lowering of cardiovascular risk means low-dose aspirin recommendations are in peril.

According to the American Diabetes Association, low-dose aspirin is a primary prevention strategy for patients with type 1 or type 2 diabetes who have an increased risk of cardiovascular disease. New research, however, shows there are no great benefits to using low-dose aspirin and even negative costs associated with aspirin use, especially among the elderly.

From 2010- 2014, men and women age 70 and older with no cardiovascular disease, dementia, or disability were enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) trial. There were 19,114 participants who were enrolled in a randomized, double-blind, placebo-controlled clinical trial. They were split into two groups: one taking 100 mg enteric coated aspirin daily and the other taking a placebo. The primary endpoints of this study found daily use of low-dose aspirin did not prolong disability-free survival among the elderly. The secondary endpoints are what we will discuss here.

The secondary endpoints of this trial were events of cardiovascular disease and major hemorrhage. Since the ADA recommends low-dose aspirin for patients with diabetes who have an increased risk of cardiovascular disease, the secondary endpoints of the ASPIREE trial are more relevant for an elderly person with diabetes. Cardiovascular disease was defined as a fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure. Hemorrhage was defined as hemorrhagic stroke, symptomatic intracranial bleeding, or clinically significant extracranial bleeding.

Intention-to-treat analyses and Cox proportional-hazards models were used to compare the aspirin group with the placebo group. After 4.7 years, the rate of cardiovascular disease did not differ much between the aspirin group and the placebo group. The aspirin group had 10.7 events per 1,000 person-years and the placebo group had 11.3 events per 1,000 person-years. Additionally, individual rates of myocardial infarction, ischemic stroke, fatal cardiovascular disease, and hospitalization for heart failure were similar in the two groups.

The rate of hemorrhage was 8.6 events per 1,000 person-years in the group who took aspirin and 6.2 events per 1,000 person-years in the placebo group.

These conclusions show that using low-dose aspirin in the elderly as a primary prevention strategy is risky and can lead to higher rates of hemorrhage. It also did not show any significantly lower cardiovascular risk compared to placebo. Current ADA guidelines do say there is limited data for low-dose aspirin use in patients with diabetes who have  cardiovascular risk yet it is still recommended. This trial showed these recommendations may need to be updated.

Practice Pearls:

• Elderly patients with diabetes who have a risk for developing cardiovascular disease should discuss negative effects of low-dose aspirin and know there is no significantly lower risk of cardiovascular disease.
• Elderly patients already taking low-dose aspirin need to monitor for signs of hemorrhage.
• According to this trial, aspirin does not have a protective effect on the heart and can increase risk of bleeding with continued use.

References:

American Diabetes Association. 9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2018. Diabetes Care. (2018), 41 (Supplement 1) S86-S104; DOI: 10.2337/dc18-S009

John J. McNeil, Rory Wolfe, Robyn L. Woods,. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. New England Journal of Medicine. (2018): DOI: 10.1056/NEJMoa1805819