Low-dose aspirin has been shown not to prolong disability-free survival in healthy individuals over 70 years of age, even in those at highest risk of cardiovascular disease (CVD).
This late-breaking result of a subgroup analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial has been reported at the European Society of Cardiology (ESC) Congress 2019 and World Congress of Cardiology taking place in Paris this week.
Christopher Reid, MD, of Curtin University, Perth, Western Australia explained that more and more people reach 70 years of age without overt cardiovascular disease (CVD). Results from this analysis suggest that improved methods for risk prediction are required to accurately identify patients who may benefit from daily low-dose aspirin.
According to Dr. Reid, these findings emphasize that the use of aspirin in healthy older men and women has a risk-benefit trade-off that varies based on individual levels of cardiovascular risk. The results also suggest that reduced cardiovascular events in the highest risk groups based on current stratification methods do not identify the individuals for whom this advantage will translate into prolonged disability-free survival.
European guidelines on the prevention of CVD do not recommend aspirin for individuals free from CVD due to the increased risk of major bleeding.
This recommendation was supported subsequently by results:
· In moderate risk patients in the Aspirin to Reduce Risk of Initial Vascular Events in patients at moderate risk of cardiovascular disease (ARRIVE) trial
· In diabetic patients in A Study of Cardiovascular Events iN Diabetes (ASCEND)
· In individuals over 70 years of age in ASPREE. These results demonstrated that modest reductions in CVD risk were outweighed by the increased bleeding hazard.
The primary finding from the randomized ASPREE trial was that in individuals age ≥70 years with no known CVD, no effect was observed of 100 mg of daily aspirin on the composite primary endpoint of disability-free survival (defined as those not reaching a primary endpoint of dementia or persistent physical disability or death).
The subanalysis examined whether results for the primary endpoint of disability-free survival might vary by the baseline level of CVD risk. Analyses were also conducted for the secondary endpoints of all-cause mortality, major hemorrhage, and prevention of CVD (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure).
Ten-year CVD risk probabilities were calculated at baseline for the 19,114 ASPREE participants using the Framingham score (up to 75 years of age) and the atherosclerotic cardiovascular disease (ASCVD) pooled cohort risk equations (up to 79 years of age).
No CVD risk scores were available beyond the age ranges specified in the equations, so they also classified participants according to the presence of zero to one, two to three, or more than three CVD risk factors.
For participants in the lowest third of CVD risk, by both Framingham and ASCVD scores, neither disability-free survival nor cardiovascular benefit was seen with aspirin. This group was also at the highest likelihood of bleeding.
In contrast, those in the highest third of CVD risk, according to both Framingham and ASCVD scores, experienced significantly lower CVD event rates with aspirin, with similar rates of bleeding.
Hazard ratios for CVD reduction with aspirin vs placebo were 0.72 (95% confidence interval, 0.54-0.95) for the group classified as high risk using the Framingham score and 0.75 (95% confidence interval, 0.58-0.97) for those defined as high risk using the ASCVD equations.
This reduction in CVD did not translate into a significantly improved disability-free survival, however. Hazard ratios for disability-free survival with aspirin vs placebo were 0.86 (95% confidence interval, 0.62-1.20) for the group designated at high risk according to the Framingham score and 0.89 (95% confidence interval, 0.62-1.28) for those considered at high risk according to the ASCVD equations.
New ways to identify groups at increased CVD risk, beyond the use of conventional risk factors and current prediction models, will be investigated in the ASPREE longitudinal follow-up study.
Dr. Reid concluded that the results of the main ASPREE trial indicate that daily low-dose aspirin should not be recommended in healthy individuals over age 70 years, regardless of CVD risk. Furthermore, the findings highlight that more refined methods are needed to identify a subgroup of individuals who may benefit from preventive therapy.