Multinational validation of the PREVENT and SCORE2 cardiovascular risk equations across 6.4 million individuals

The American Heart Association's PREVENT equations estimate risk of total cardiovascular disease (CVD), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) to guide lipid-lowering and blood pressure-lowering therapy in people ages 30-79 years in the United States. The SCORE2 risk algorithm is used to estimate CVD risk for similar purposes in people ages 40 and older in Europe. Neither set of equations has been comprehensively validated in global observational cohorts and randomized trials. In this study, in 44 observational cohorts and 18 randomized trials, we assessed discrimination and calibration of the two risk algorithms across geographical regions (North America, Europe and Asia/Other or multiregional trials). We also created scaling factors for risk prediction over 1-9 years using the PREVENT equations, enabling shorter-term risk prediction for research purposes or to facilitate clinical trial enrollment. Over 5.1 years of mean follow-up, 293,737 PREVENT total CVD events (fatal and non-fatal ASCVD or HF) and 258,086 SCORE2 CVD events (myocardial infarction, stroke or cardiovascular death) were observed among 6,422,714 and 5,437,384 individuals, respectively. Despite differences in CVD outcome definitions, target populations and predictor variables, overall discrimination and calibration were similar for both equations, with generally good performance across regions, including in multiregional randomized trials. These findings lend support for adoption of PREVENT or SCORE2 for cardiovascular risk stratification across diverse settings.