A State Transition Model for Health Outcomes Associated with Vorapaxar Treatment as an Add-on to Standard Care Antiplatelet Therapy in the Prevention of Thrombotic Events for Patients with a Recent Myocardial Infarction.
BACKGROUND
The TRA 2°P-TIMI 50 trial showed the addition of vorapaxar to standard care (SC) antiplatelet therapy reduced the combined risk of death, myocardial infarction (MI), and stroke, while exhibiting an increase in moderate, but not other bleeding events.


OBJECTIVE
Our objective was to estimate the long-term health benefits and risks of vorapaxar as an add-on to SC treatment (lifetime aspirin and up to 12 months of clopidogrel) for patients with a prior MI and without a history of cerebrovascular disease.


METHODS
In the state transition model we developed, the patients transition between states due to recurrent MI, stroke, or death, and are at risk of non-fatal bleeding. Risk equations were developed from individual patient-level data from the TRA 2°P-TIMI 50 trial to predict long-term cardiovascular (CV) outcomes. Additional sources informed inputs for case fatality, bleeding rates on SC, risk of non-CV death, and utilities.


RESULTS
Over a lifetime horizon, fewer CV events and more bleeding events occurred in the vorapaxar (VOR) + SC arm, relative to the SC-only arm. These results were ultimately accompanied by an increase in life expectancy and health benefits associated with add-on vorapaxar treatment, as the VOR + SC arm yielded an average of 8.27 discounted quality-adjusted life-years (QALYs) compared with an average of 7.96 discounted QALYs in the SC-only arm.


CONCLUSIONS
This model framework leveraged novel risk equations to make long-term projections of CV events in a population at high risk of recurrence. Model results suggest vorapaxar is most effective as add-on therapy to SC antiplatelet treatment when initiated upon hospital discharge post-MI.
Evidera, Metro Building, 6th Floor, 1 Butterwick, London, W6 8DL, UK.
John D
JD
Whalen
Merck & Co., Inc., 351 North Sumneytown Pike, North Wales, PA, 19454, USA.
Glenn
G
Davies
Evidera, 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD, 20814, USA.
Mark
M
Du
Evidera, Metro Building, 6th Floor, 1 Butterwick, London, W6 8DL, UK. mustafa.oguz@evidera.com.
Mustafa
M
Oguz
Merck & Co., Inc., 126 East Lincoln Avenue, Rahway, NJ, 07065, USA.
Lori D
LD
Bash
Evidera, 430 Bedford Street, Suite 300, Lexington, MA, 02420, USA.
Ipek
I
Ozer-Stillman
D001241:Aspirin / Q000627:therapeutic use; D002319:Cardiovascular System / Q000187:drug effects; D000077144:Clopidogrel; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D055502:Secondary Prevention / Q000379:methods; D020521:Stroke / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; C530299:vorapaxar