Coronary Artery Calcium in the PRagmatic EValuation of evENTs And Benefits of Lipid lowering in the Elderly: CAC PREVENTABLE Ancillary Study
Biography
Overview
ABSTRACT Predicting risk is critical for effective primary prevention of atherosclerotic cardiovascular disease (ASCVD), however classifying risk in adults ?75 years of age remains extremely challenging. Coronary artery calcium (CAC) scoring and high-sensitivity troponin (hs-Tn) are promising tools for risk stratification in older adults because they provide singular and enduring snapshots that directly quantify a composite of cumulative risk factor exposure and individual resiliency or vulnerability. Used jointly, we have shown that low values of CAC and hs-Tn may be useful for ?de-risking? older populations, identifying individuals with highly favorable prognosis in whom preventive therapy may not be beneficial. However, despite promising observational data, the true clinical value of CAC and hs-Tn in older adults remains uncertain due to lack of a dedicated, adequately powered randomized trial. The NIA/NHLBI-funded PREVENTABLE (PRagmatic EValuation of evENTs And Benefits of Lipid-lowering in oldEr adults) pragmatic clinical trial, which is currently randomizing 20,000 adults ?75 years of age to atorvastatin 40mg or placebo and following for ASCVD events, provides the ideal setting to test the critical hypothesis that CAC and hs-Tn jointly identify older adults who will benefit the most, and the least, from statin therapy. In this proposal, we seek to perform baseline CAC scanning and hs-Tn measurement in 10,000 PREVENTABLE participants. At trial conclusion, we will conduct analyses stratified by CAC, and jointly by CAC and hs-Tn, with >85% power to determine heterogeneity of statin effect by biomarker status. At the end of the trial, we will develop a comprehensive ASCVD risk classification model using traditional risk factors, CAC, and hs-Tn and validate this in MESA and ARIC. We will then construct an online tool similar to the LIFE-CVD model for calculating estimated benefit of statin therapy in the age ?75 primary prevention population, after detailed accounting for non-CVD competing risks observed in PREVENTABLE. In summary, we believe that CAC scanning and hs-Tn measurement in PREVENTABLE is the most expeditious and instructive way to fill critical knowledge gaps about subclinical ASCVD in an older primary prevention population and to determine the value of a biomarker-guided precision medicine approach for informing individual benefit of preventive statin therapy.
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