Can PEGASUS-TIMI 54 eligible criteria discriminate the risk of long-term major cardiovascular adverse events in patients with prior myocardial infarction in the real-world practice?

Abstract

Background In the PEGASUS-TIMI 54 trial, the long-term use of low-dose ticagrelor in addition to aspirin in patients with prior myocardial infarction (MI) more than 1 year could reduce the composite endpoints of major adverse cardiac events (MACE). However, it came with the expense of bleeding complication compared with the patients taking aspirin alone. Purpose We sought to describe the proportion of patients who would have benefit from low-dose ticagrelor according to the PEGASUS-TIMI 54 trial and to explore the long-term prognosis of those patients in comparison with the patients who did not meet the trial criteria in the real-world practice. Method The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicentre, observational, longitudinal study of Thai patients with high atherosclerotic risk. The study included the patients with established coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral arterial disease (PAD), or with at least three atherosclerosis risk factors. The PEGASUS-TIMI 54 inclusion and exclusion criteria were applied to the CORE-Thailand population and stratified the patients into 4 groups as follows; prior MI patients with PEGASUS-TIMI 54 eligible criteria (PE group); prior MI patients without PEGASUS-TIMI 54 eligible criteria according to the time of index MI occurred <1 year (NP1 group), 1–3 years (NP1–3 group) and >3 years (NP3 group). The baseline characteristics and the incidence of MACE (cardiovascular death, MI or stroke) according to the PEGASUS TIMI-54 trial were compared among the four groups. Results From the 9,390 enrolled patients, 2,109 had prior MI. Six hundred and ninety-nine (33.1%) of the patients were stratified to the PE group whereas 15.7%, 14.7% and 36.5% were NP1, NP1–3 and NP3, respectively. The incidence of MACE at 730 days in the PE group was 5.2% followed by 4.5%, 2.9%, 2.2%, in the NP1 group, NP3 group and NP1–3, respectively. Interestingly, the incidence of MACE in NP 1–3 group and NP3 were comparable between the groups, p=0.53. When compared the MACE rates between the PE group the NP1–3 group, the PE group significantly experienced MACE more than the NP1–3 group (hazard ratio [HR] 2.34, confidence interval [CI] 1.95–5.28; p=0.039). The incidence of all-cause death in the PE group was also higher than the NP1–3 (5.2% vs. 2.2%, HR 2.37 CI 1.05–5.33, p=0.037). Conclusion The proportion of the patients in the CORE-Thailand registry who would have benefit from the low-dose ticagrelor represent in one-third of the entire population reflecting that the external applicability of the PEGASUS in the CORE-Thailand registry is feasible. The presence of PEGASUS-TIMI 54 eligible criteria is associated with the higher MACE rates and all-cause mortality compared with the patients who had prior MI between 1 and 3 years but did not meet trial criteria. Cumulative incidence of MACE Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Heart Association of Thailand under the Royal Patronage of H.M. the King and the National Research Council of Thailand