title: State transition model: vorapaxar added to standard antiplatelet therapy to prevent thrombosis post myocardial infarction or peripheral artery disease.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: a Evidera , Bethesda , MD , US.
authors.forename: Mark
authors.initials: M
authors.lastname: Du
authors.affiliation: b Merck & Co. Inc. , North Wales , PA , US.
authors.forename: Monica
authors.initials: M
authors.lastname: Chase
authors.affiliation: c Evidera , London , UK.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Oguz
authors.affiliation: b Merck & Co. Inc. , North Wales , PA , US.
authors.forename: Glenn
authors.initials: G
authors.lastname: Davies
mesh_terms: D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D000077144:Clopidogrel; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D058729:Peripheral Arterial Disease / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D055502:Secondary Prevention / Q000379:methods; D020521:Stroke / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; C530299:vorapaxar
keywords: Antiplatelet therapy; Secondary prevention; State transition model; Vorapaxar