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Abstract
Objective: To evaluate long-term health benefits and risks of adding vorapaxar (VOR) to the standard care antiplatelet therapy (SC) of aspirin and/or clopidogrel, among a population with a recent myocardial infarction (MI) and/or peripheral artery disease (PAD).
Research design and methods: In a state-transition model, patients transition between health states (event-free, recurrent MI, stroke, death), while at risk of experiencing non-transition-related revascularization and non-fatal bleeding events. Risk equations developed from the TRA 2°P-TIMI 50 trial’s patient-level data were used to predict cardiovascular (CV) outcomes over longer time horizons. Additional sources, including trials and US-based observational studies, informed the inputs for short-term CV risk, non-CV death, and health-related quality of life. Survival and quality-adjusted life-years (QALYs) were estimated over a lifetime horizon, discounted at 3% per year.
Results: Within a cohort of 7361 patients with recent MI and/or PAD, VOR + SC relative to SC alone yielded 176 fewer CV events (MIs, strokes, or CV deaths), but 27 more major bleeding events. VOR + SC was associated with increased life expectancy and health benefits (19.93 undiscounted life-years [LYs], 9.57 discounted QALYs vs. 19.61 undiscounted LYs, 9.41 discounted QALYs). The results were most sensitive to scenarios varying time of vorapaxar initiation, and the assumptions in the 90 day period post-MI. Additional analyses showed that add-on vorapaxar provides consistent incremental benefits in high-risk subgroups.
Conclusion: This study contributes to the growing literature on secondary prevention add-on therapy, as results from these modeling analyses suggest that adding vorapaxar to SC for patients at high atherothrombotic risk can provide long-term health benefits.
Transparency
Declaration of funding
Merck & Co. Inc. provided the funding for the project and manuscript and also provided the funding to publish this paper as a Sponsored Focus article.
Author contributions: M.D. and M.O. were responsible for the design of the model, in addition to carrying out the implementation of the model design, identifying data sources, conducting the modeling analyses, and drafting the content of the manuscript. G.D. and a team of statisticians at Merck & Co. Inc. developed the risk equations from individual patient-level TRA 2°P data. M.C. and G.D. provided strategic oversight on the implementation, guidance on sources, key assumptions, analyses conducted and interpretation and development of the manuscript. Each author contributed to the interpretation of the results, and has reviewed and approved the final version of the manuscript.
Declaration of financial/other relationships
M.C. and G.D. have disclosed that they are employees and shareholders of Merck & Co. Inc. M.D. and M.O. have disclosed that they are employees of Evidera, which provides consulting and other research services to pharmaceutical, medical device, and other related organizations. In their positions as salaried employees, they work with a variety of companies and clients, and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from Merck & Co. Inc.
CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
The authors would like to extend many thanks to John Whalen and Ipek Stillman, two former employees of Evidera. The model structure outlined in this study included components from the secondary prevention model they helped develop, which focused on a recent MI population, that also leveraged individual-level patient data from the TRA 2°P-TIMI 50 trialCitation11. Thanks also to Janet Dooley of Evidera Inc. for her assistance with the editing and production of this paper.