Reduction in Subtypes and Sizes of Myocardial Infarction With Ticagrelor in PEGASUS-TIMI 54

Abstract

Background Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS-TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention-related (Type 4a) and coronary artery bypass graft-related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥100× upper limit of normal. A total of 21% (224) were ST-segment-elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72-0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥100× upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53-0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46-0.78, P=0.0002). Conclusions In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01225562.

Keywords: ST‐segment elevation myocardial infarction; antiplatelet therapy; myocardial infarction; ticagrelor; troponin.

Figure 1

A, Distribution of myocardial infarction events occurring during follow‐up by Universal Definition of MI subtype. B, Distribution of myocardial infarction events occurring during follow‐up by fold elevation in peak biomarker (includes 913 events with troponin available). CABG indicates coronary artery bypass grafting surgery; MI, myocardial infarction; PCI, percutaneous coronary intervention; Tn, troponin; ULN, upper limit of normal.

Figure 2

Myocardial infarction occurring over 3 years by randomized treatment. CI indicates confidence interval; HR, hazard ratio; MI, myocardial infarction.

Figure 3

Reduction in MI by treatment (red—ticagrelor 90 mg twice daily, blue—ticagrelor 60 mg twice daily, purple—ticagrelor doses pooled) for MI overall and by MI subtype. CI indicates confidence interval; HR, hazard ratio; KM, Kaplan–Meier; MI, myocardial infarction; PCI, percutaneous coronary intervention.

Figure 4

Reduction in MI by treatment (red—ticagrelor 90 mg twice daily, blue ticagrelor 60 mg twice daily, purple—ticagrelor doses pooled) for MI overall and by fold elevation of peak biomarker. CI indicates confidence interval; HR, hazard ratio; KM, Kaplan–Meier; MI, myocardial infarction; Tn, troponin; ULN, upper limit of normal.

Figure 5

STEMI occurring over 3 years by randomized treatment. CI indicates confidence interval; HR, hazard ratio; STEMI, ST‐segment–elevation myocardial infarction.