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.

• Authors: Marc P Bonaca, Stephen D Wiviott, David A Morrow, P Gabriel Steg, Christian Hamm, Deepak L Bhatt, Robert F Storey, Marc Cohen, Julia Kuder, KyungAh Im, Giulia Magnani, Andrzej Budaj, José C Nicolau, Alexander Parkhomenko, José López-Sendón, Mikael Dellborg, Rafael Diaz, Frans Van de Werf, Ramón Corbalán, Assen Goudev, Eva C Jensen, Per Johanson, Eugene Braunwald, Marc S Sabatine
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 7 Issue 22 Pg. e009260 (11 20 2018) ISSN: 2047-9980 [Electronic] England
• PMID: 30571502 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet Aggregation Inhibitors
• Ticagrelor

Topics

• Aged
• Death, Sudden, Cardiac (prevention & control)
• Humans
• Middle Aged
• Myocardial Infarction (pathology, prevention & control)
• Platelet Aggregation Inhibitors (therapeutic use)
• ST Elevation Myocardial Infarction (pathology, prevention & control)
• Ticagrelor (therapeutic use)