Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction

Abstract

Background: Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. Methods: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. Results: The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components ( P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1–2 risk indicators; 61%) had a 2.1% absolute risk reduction ( P <0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups ( P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. Conclusions: Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00526474.

American Heart Association's Life's Simple 7 at Middle Age and Prognosis After Myocardial Infarction in Later Life

“…We implemented 3 main models to evaluate the impact of potential confounders. Model 1 was adjusted for the following: age at MI, sex, race, calendar year of incident MI (<1995, 1995–2004, and ≥2005), clinical predictors at admission for poor prognosis in patients with MI19 (a history of heart failure, stroke, coronary artery bypass graft, peripheral artery disease, and kidney dysfunction (estimated glomerular filtration rate of <60 mL/min per 1.73 m 2 within 1 year before MI or diagnosed chronic kidney disease), hypertension, diabetes mellitus, and current smoking at admission. We also further adjusted for health insurance at baseline (model 2a) and admission (model 2b).…”

International Validation of the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention in Post‐MI Patients: A Collaborative Analysis of the Chronic Kidney Disease Prognosis Consortium and the Risk Validation Scientific Committee

“…These 5 studies included the ARIC and the RCAV (Racial and Cardiovascular Risk Anomalies in CKD Cohort) from the United States, the SCREAM (Stockholm Creatinine Measurements Cohort) from Sweden, the KHS (Korean Heart Study) from South Korea, and the NZDCS (New Zealand Diabetes Cohort Study) from New Zealand. A total of 53 599 patients with recent acute MI who survived at least 2 weeks from index date of MI were included in this study, to be in line with inclusion criteria of the derived study population of TRA2°P (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Event)‐TIMI50 10. Details of the study design and the approach for identifying recent MI cases in each cohort are summarized in Data S1 and S2.…”

“…The following 9 predictors in TRS2°P were identified in each of the 5 studies (Data S1): heart failure (yes versus no), hypertension (yes versus no), age (≥ versus <75 years), diabetes mellitus (yes versus no), prior stroke (yes versus no), prior coronary artery bypass grafting (CABG) (yes versus no), peripheral artery disease (yes versus no), reduced kidney function (estimated glomerular filtration rate < versus ≥60 mL/min per 1.73 m 2 ), and current smoking (yes versus no) 10. We calculated estimated glomerular filtration rate using the creatinine equation from the Chronic Kidney Disease Epidemiology Collaboration 15.…”

“…Of importance, a large risk variation is recognized among patients with MI depending on demographics, comorbidities, and severity of MI 6, 7. Risk stratification is important because it may influence the selection of secondary preventive therapy, such as intensive antiplatelet therapy where benefit may only outweigh harm in higher risk patients but not among lower risk ones 8, 9, 10. In this context, the Thrombolysis in Myocardial Infarction (TIMI) Study Group recently developed a simple scoring system, the TIMI Risk Score for Secondary Prevention (TRS2°P) 10.…”

“…Risk stratification is important because it may influence the selection of secondary preventive therapy, such as intensive antiplatelet therapy where benefit may only outweigh harm in higher risk patients but not among lower risk ones 8, 9, 10. In this context, the Thrombolysis in Myocardial Infarction (TIMI) Study Group recently developed a simple scoring system, the TIMI Risk Score for Secondary Prevention (TRS2°P) 10. This risk stratification tool is for classifying the risk of secondary outcomes among patients with recent MI, using 9 clinical and behavioral factors readily available in clinical practice.…”