Pharmaco-invasive strategy and dosing of tenecteplase in STEMI patients 60 to <75 years: An inter-trial comparison of the STREAM-1 and STREAM-2 trials

Abstract

Background Previous studies indicate a safety risk with full-dose TNK in elderly patients. In a study of patients >= 60 years STREAM-2 (STrategic Reperfusion Early After Myocardial infarction-2), a pharmaco-invasive (PI) strategy with half-dose TNK was similar (in efficacy and safety) to primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients presenting < 3 hours. While no treatment difference +/- 75 years was observed, the role of this half-dose PI strategy in patients < 75 years is unknown. In this comparison of STEAM-1 and-2, we analyzed PI strategies with full-dose (STREAM-1) versus half-dose TNK (STREAM-2) to evaluate their relative efficacy and safety in this younger STEMI cohort. Methods We evaluated patients 60 to < 75 years from STREAM-1 and STREAM-2 receiving PI treatment versus PPCI for their resolution of ST-elevation after fibrinolysis and angiography, primary efficacy composite of 30-day all-cause death, myocardial infarction, heart failure, and shock, and safety events. Results Among 1103 patients, 327 received a full-dose PI strategy (STREAM-1), 289 a half-dose PI strategy (STREAM- 2) and 487 PPCI (338 in STREAM-1; 149 in STREAM-2). Half- compared to full-dose TNK resulted in similar proportions of patients achieving ST resolution >= 50% (71.2% vs 68.7%, P = . 519): their ICH risks were 2.1% vs 1.5%, P = . 605 respectively). Following angiography, PI patients had nominally better ST resolution >= 50% compared to their PPCI counterpart (STREAM-1: 87.7% vs. 83.2%, P = . 120; STREAM-2: 88.2% vs. 81.0%, P = . 048) with similar primary composite outcome at 30 days (STREAM-1: 14.4% vs. 16.3%, 0.90 [0.62, 1.31]; STREAM-2: 9.0% vs 8.1%, 1.29 [0.64, 2.61]). Major (nonICH) bleeding markedly declined in STREAM-2 compared to STREAM-1 in both treatment groups (STREAM-1: 7.1%vs. 6.0%; STREAM-2: 0.3% vs. 0.7%). Conclusions In STEMI patients 60 to < 75 years presenting within 3 hours of symptoms, half-dose PI treatment appears as efficacious as a full-dose PI strategy with a low systemic bleeding risk. Half-dose PI treatment deserves consideration when timely PPCI is not attainable in this important STEMI sub-group. Clinicaltrials.gov registration numbers NCT00623623, NCT02777580.