Efficacy and Safety of Aspirin for Primary Cardiovascular Risk Prevention in Younger and Older Age: An Updated Systematic Review and Meta-analysis of 178,310 Subjects from 21 Randomized Studies

Calderone et al.

Thromb Haemost
DOI: 10.1055/a-1667-7427

Why did you (and your colleagues) write this paper? What was its main purpose? 

DARIO CALDERONE:

The use of aspirin for primary cardiovascular prevention is a matter of controversy in the cardiovascular field, with recent evidence highlighting questionable net benefit. None of the most recent meta-analyses included the large-scale TIPS-3 trial, published in 2020, where aspirin was compared with placebo in patients who did or did not receive a polypill comprising other drugs for primary cardiovascular disease prevention. Moreover, based on the results of the recent ASPREE trial that showed an increased mortality risk with aspirin use when compared to placebo in the elderly population, we hypothesized the chance of a gradient of net benefit with aspirin use (i.e., larger in younger individuals and null in older patients) based on age. As such, we decided to run an updated meta-analysis of aspirin for primary cardiovascular prevention, now including the TIPS-3 trial, focusing in particular on age as a treatment modifier. 

What are the main conclusions? 

DARIO CALDERONE:

We confirmed the lack of efficacy with aspirin use for reducing all-cause mortality, with modest protection on nonfatal ischemic events and higher risk of haemorrhagic complications compared with no aspirin or placebo. In the age analysis, we concluded for a small but larger net benefit of aspirin in younger (<65 years old) compared with older individuals (≥65 years old). 

What are the paper’s implications?- to the public?-to medical professionals?

DARIO CALDERONE:

Based on our findings, we believe that aspirin does not represent a viable option for most patients without overt cardiovascular atherosclerotic disease. However, for those patients where the risk-benefit suggests using aspirin for primary cardiovascular prevention, age should factor into the decision-making equation. Both physicians and patients should be aware of the benefits and risks of aspirin use in relation to age. 

Are the findings clinically significant? Should the findings change practice? 

DARIO CALDERONE:

We believe that our results with respect to the effect of aspirin by age for primary cardiovascular prevention may meaningfully inform current practice. Both the 2019 ACC/AHA guidelines and the 2021 U.S. Preventive Services Task Force recommendations now use age as a criterion for aspirin use, while the 2021 ESC guidelines on prevention did not provide age-specific consideration. Our metanalysis reinforces the concept that age should be considered as a treatment modifier when this option is considered in selected candidates where the risk of thrombotic complications raises concerns and the risk of bleeding is low. As such, we hope that our findings will help physicians in better discerning this benefit/risk ratio. 

Aspirin for Primary and Secondary Prevention of Cardiovascular Disease: Time to Stop?

John G. F. Cleland

Thromb Haemost
DOI: 10.1055/s-0041-1740639