Coronary Artery Calcium in the PRagmatic EValuation of evENTs And Benefits of Lipid lowering in the Elderly: CAC PREVENTABLE Ancillary Study
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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.
