Characteristics, risk factor profiles, and cardiovascular outcomes in patients with ASCVD without prior ischemic events in Western Europe: The OPTIMUS-RISK Study

Background Patients with atherosclerotic cardiovascular disease (ASCVD) are considered at very high risk for major adverse cardiovascular events. However, most clinical evidence has been generated in individuals with a history of acute ischemic events (myocardial infarction or stroke). Consequently, the characteristics, risk factor profiles, and rates of cardiovascular outcomes in patients without prior ischemic events remain insufficiently characterized. Methods OPTIMUS-RISK (Outcomes and PrevenTIon program with PCSK9i Monoclonal antibodies in ASCVD PopUlation without prior iSchemic events) is an observational study program using data representing routine clinical practice from three Western European countries: Spain (Telotron), Italy (Fondazione ReS), and The Netherlands (PHARMO). Individuals with incident ASCVD (first diagnosis with a clean pre-period) were identified; the first ASCVD diagnosis served as the index date. Patients with ischemic events at or prior to index, or within 14 days after index, were excluded. To establish a valid at-risk period and avoid immortal time bias, follow-up began 14 days after index. The primary endpoint was a composite of myocardial infarction, ischemic stroke, and all-cause mortality. Patients were censored at the last day of available follow-up (i.e. lost to follow-up or end of study period). Results Among the starting pool of all individuals with incident ASCVD, approximately 50% had no prior acute ischemic event. A total of 17,857, 93,061, and 179,349 individuals met the inclusion criteria in the Telotron, Fondazione ReS, and PHARMO databases, respectively. Mean age was 68.6, 71.8, and 66.5 years, and the proportion female was 40.6%, 36.8%, and 46.3%, respectively. Diabetes was present in 31.4%, 31.3%, and 17.8%; hypertension in 67.2%, 64.2%, and 55.8%; and chronic kidney disease in 15.3%, 10.9%, and 10.1%, respectively. Stable angina was recorded in 30.9%, 17.0%, and 22.7%, and peripheral artery disease in 32.5%, 20.8%, and 24.4%, respectively. The 5-year Kaplan-Meier cumulative incidence (95% CI) of the primary endpoint was 28.8% (28.0–29.6%), 23.2% (22.9–23.6%), and 21.8% (21.6–22.1%), respectively. Conclusion Individuals with ASCVD without prior ischemic events across Western Europe exhibit a high burden of cardiovascular risk factors and substantial long-term risk of ischemic events or death following their initial diagnosis. These findings underscore the need for optimization of risk-factor management to reduce the burden of adverse outcomes in this understudied population.