Time to reconsider aspirin for primary cardiovascular disease prevention
Use of aspirin in the primary prevention of cardiovascular disease (CVD) in patients with no prior CVD history yields protection against the risks of acute myocardial infarction (AMI) and ischaemic stroke, but at the expense of an increase of similar magnitude in the incidence of major bleeding, according to the results of a recent meta-analysis presented at the European Society of Cardiology (ESC) Congress 2019 in Paris, France.
The lack of net benefit of aspirin “makes it necessary to reconsider its use in this population,” said principal investigator Dr Lorenzo Martin Lobo from the Campo de Mayo Military Hospital in Buenos Aires, Argentina.
Lobo and colleagues performed an updated meta-analysis that included 13 trials on the risk–benefit relationship of aspirin use in primary CVD prevention, including three mega trials published last year, namely ASCEND*, ARRIVE** and ASPREE***.
All studies showed excellent quality according to Jadad’s scale (≥3 points for each trial), and there were no publication biases observed. The overall study population comprised 164,225 patients, of whom 82,900 were in the aspirin arm and 81,325 in the control arm, with a median follow-up of 5 years.
Patients were stratified based on their CVD risk at a 10-year incidence: low (<10 percent), moderate (10–20 percent) and high (>20 percent). Eight studies included low-risk patients, and five studies involved moderate/high-risk populations.
Pooled data showed that aspirin use led to a reduction in the primary endpoint of a composite of CV death, AMI and ischaemic stroke in the entire population (odds ratio [OR], 0.90, 95 percent CI, 0.85–0.94; I2, 0 percent; p=0.73). This protective benefit was observed consistently in low- (OR, 0.88, 0.82–0.94; I2, 0 percent; p=0.79) and moderate/high-risk subgroups (OR, 0.92, 0.85–0.99; I2, 6 percent; p=0.37). [ESC 2019, abstract P667]
On individual analysis of each of the events using random effects model, aspirin was beneficial against AMI (OR, 0.86, 0.73–0.97; I2, 53.3 percent; p=0.01) and ischaemic stroke (OR, 0.90, 0.83–0.98; I2, 13.4 percent; p=0.31) only. CV mortality did not significantly differ relative to that in the control arm (OR, 0.94, 0.86–1.04; I2, 20.5 percent; p=0.24).
Furthermore, the primary safety endpoint of major bleeding was significantly higher in the aspirin arm (OR, 1.45, 1.34–1.56; I2, 29.3 percent; p=0.15). This bleeding risk remained elevated in subgroups of low- (OR, 1.43, 1.32–1.55; I2, 40 percent; p=0.11) and moderate/high-risk patients (OR, 1.51, 1.28–1.78; I2, 19 percent; p=0.29).
Current European guidelines do not endorse the use of aspirin for primary prevention of CVD in patients with diabetes and those who do not have any prior history of established cardiovascular disease. Likewise, in March 2019, the American College of Cardiology (ACC) and the American Heart Association (AHA) released its updated guidelines discouraging the use of the drug for the routine primary prevention of atherosclerotic CVD in most adults because of lack of net benefit. [Eur Heart J 2016;37:2315–2381; http://www.onlinejacc.org/sites/default/files/additional_assets/guidelines/Prevention-Guidelines-Made-Simple.pdf]
*A Study of Cardiovascular Events in Diabetes
**Aspirin to Reduce Risk of Initial Vascular Events
***Aspirin in Reducing Events in the Elderly