Abstract
Introduction: Despite aggressive secondary prevention, a persistent risk of cardiovascular (CV) events exists among patients with coronary artery disease (CAD). In addition to traditional risk factors, this residual risk results, at least in part, from persistent pro-inflammatory and metabolic contributors. This study evaluated the incidence of recurrent CV events in contemporary CV outcome trials between 2010-2021. Methods: A total of 45 randomised, controlled trials were included. Studies were categorized based on patient population and enrollment strategy into 3 groups: 1) Early post-ACS (enrolled within 72h of event), 2) late post-ACS (enrolled after 72h of event), and 3) chronic CAD or risk equivalent (type 2 diabetes or 2 or more CV risk factors). Due to a wide range of follow-up durations, data were normalized to events per 100 patient-years. Results: Follow-up duration ranged from 30 to 2957 days. Overall, recurrent CV events varied between 2% and 10%. Trials that enrolled patients within 72h of ACS demonstrated the highest risk for recurrent events with a median of 21.8 events per 100 patient-years (IQR 11.3-66.0). Patients enrolled >72h after ACS had significantly lower risk with a median of 3.4 events per 100 patient-years (IQR 2.9-4.1), likely due to a survival bias in those enrolled later after their index event. The rate of recurrent events was comparable between trials that enrolled patients 72h post-ACS and trials that enrolled patients with chronic CAD. There was no correlation between trial year and event rate. Conclusions: Despite standard of care therapy, there is a persistent residual risk of recurrent events especially early after ACS. Our study demonstrates a residual risk ranging from 3 to as high as 22 events per 100 patient-years. This risk is likely higher in a non-trial setting where medication adherence and follow-up are not strictly controlled. Novel strategies for secondary prevention comprise a major unmet need to further decrease this risk.
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