PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) affects 70% of older adults and remains the leading cause of morbidity and mor- tality in the United States. Several new drugs have recently been approved for CVD, but not enough is known about their utilization, benefits and risks in frail older patients. Since conducting a clinical trial in frail older adults can be costly and impractical, there is a pressing need for innovative strategies to generate evidence on new CVD drugs in a timely manner. The objective of this application is to establish a near-real-time prospective monitoring program in Medicare data to evaluate the benefit of new CVD drugs for older adults with frailty. A prospective monitoring program seeks to find early effectiveness and safety signals of new drugs by updating the analysis at regular intervals as new Medicare data become available. The investigators will incorporate a novel claims-based frailty index into the monitoring program to generate timely evidence on disease-specific and patient-centered net benefit of new drugs by frailty status. The central hypothesis is that disease-specific benefit and net benefit are determined by a patient's degree of frailty. Disease-specific benefit will be evaluated using clinical trial endpoints of effectiveness (e.g., CVD events) and safety (e.g., bleeding), and net benefit in terms of the number of days alive and spent at home, or “home time”. To conduct this work, the investigators will analyze Medicare data on 6 new CVD drugs approved in 2011-2017: 3 anticoagulants vs warfarin for atrial fibrillation, 2 antiplatelets vs clopidogrel for atherosclerotic CVD, and an angiotensin receptor-neprilysin inhibitor vs enalapril for systolic heart failure. The validity and reproducibility of the results will be enhanced through the linkage of a subset of Medicare data to electronic health records and a national survey to supplement clinical information, and external validation of the Medicare data analysis in 2 large commercial databases. In the next 4 years, the investigators will accomplish 3 specific aims: 1) evaluate the temporal trends and predictors of new CVD drug use in frail and non-frail older adults with CVD over 2011-2020; 2) determine disease-specific benefit (deaths, CVD and safety events) and net benefit (home time) of 6 new CVD drugs compared with alternative therapies; 3) identify patient characteristics that can predict net benefit (home time) with new CVD drugs compared with alternative therapies. This proposal's innovative approach, which combines near-real-time prospective monitor- ing, a claims-based frailty score, and the patient-centered outcome of home time, offers a readily scalable and feasible framework for comparative effectiveness and safety studies of newly approved medications. The impact of the proposed research is significant because timely evidence generated from real-world healthcare data can enable clinicians to optimize prescribing of new CVD drugs based on a patient's frailty and expected net benefit.

PROJECT NARRATIVE The proposed research aims to establish a prospective monitoring program for newly approved cardiovascular drugs for older adults with frailty in routine healthcare databases and identify predictors of benefit from the new drugs. This research is relevant to public health because the evidence generated from this work can enable clinicians to optimize prescribing of new cardiovascular drugs in older adults based on a patient's frailty level and expected net benefit. Thus, it accomplishes the National Institute on Aging's missions and initiatives by promoting effective and safe drug therapy in older adults.