Abstract 372: Health Outcomes Associated With Triple Antiplatelet Therapy for the Secondary Prevention of Atherothrombotic Events

Abstract

Vorapaxar is a protease-activated receptor-1 (PAR-1) antagonist indicated for the reduction of atherothrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD), based on the findings of the TRA 2°P-TIMI 50 trial for patients without a history of stroke or transient ischemic attack. This analysis evaluated the health outcomes of triple antiplatelet therapy with vorapaxar when added to a standard care regimen of clopidogrel plus aspirin (ASA) in comparison with standard care alone, for patients without a history of transient ischemic attack or stroke who survived hospitalization for a qualifying MI. A cohort-level state-transition model was developed in Microsoft Excel to estimate membership in health states over a lifetime time horizon: event-free, post-MI, post-stroke, dead due to bleeding, dead due to CV causes, and dead due to other causes. Predictive equations were developed from patient-level data from TRA 2°P, in order to estimate CV event-related transition probabilities, based on patient characteristics. These improve upon Framingham risk equations as they consider the time since the most recent myocardial infarction, and they are based on a greater number of CV events from a larger and more diverse population. Meta-analyses, national statistics, and other publications were used to estimate case fatality and bleeding rates, the risk of non-CV mortality, as well as utilities for estimation of quality-adjusted life years (QALYs). For validation, the risk equation and model results were compared with the observed event rates in TRA 2°P, risk estimates from Framingham Heart Study publications, as well as QALY and life-year outcomes from other published models. Over a lifetime time horizon, the model predicted 8.3 fewer recurrent MIs, 3.8 fewer strokes, and 18.2 fewer CV deaths in the vorapaxar plus standard care arm in comparison with standard care alone, per 1,000 patients treated, with an increase of 26.4 transfusions, 3.6 intracranial hemorrhage, and 0.9 fatal bleeding events. Discounted life-years and QALYs increased by 0.4 and 0.3 respectively with vorapaxar treatment. In validation, modeled CV event counts were within 0.1% of the observed rates in TRA 2°P. The model’s prediction of 8.94 QALYs in the standard care arm is comparable to the prediction of 9.55 to 9.78 QALYs in a recent UK model of antiplatelet monotherapy after MI. Based on model results, triple antiplatelet therapy with vorapaxar provides additional clinical benefit versus standard care after MI, for a patient population that is at high risk for recurrent and potentially fatal events. In validation, the model yielded projections of CV morbidity and mortality comparable to the observed outcomes from the TRA 2°P clinical trial, Framingham equations, and other models.