EFFICACY AND SAFETY OF A ROUTINE EARLY INVASIVE STRATEGY IN RELATION TO TIME FROM SYMPTOM ONSET TO FIBRINOLYSIS: A SUBGROUP ANALYSIS FROM TRANSFER-AMI

Abstract

Randomized controlled trials have demonstrated the clinical benefit of a routine early invasive strategy in patients receiving fibrinolysis for ST-elevation myocardial infarction (STEMI). However, the treatment effect of fibrinolysis is highly time sensitive - efficacy decreases as the time interval from symptom onset to fibrinolysis lengthens. Whether the effect of a routine early invasive strategy, as an adjunct to fibrinolysis, also varies in relation to this time interval is not well understood. We therefore sought to evaluate the efficacy and safety of a routine early invasive strategy in relation to time from symptom onset to fibrinolysis. The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1059 STEMI patients to an early invasive strategy - consisting of routine early transfer for coronary angiography and percutaneous coronary intervention (PCI) if needed within 6 hours of fibrinolysis - or standard therapy post-fibrinolysis. The primary endpoint was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post-hoc subgroup analysis of TRANSFER-AMI, we evaluated efficacy and safety outcomes after stratification by the time elapsed from symptom onset to fibrinolysis (<2 vs ≥2 hours). Of 1059 patients (median age 57 years, 80% male), 557 (53%) and 502 (47%) received fibrinolysis <2 hours (median 1.25 hours, IQR 0.97-1.58 hours) and ≥2 hours (median 3.24 hours, IQR 2.43-4.80 hours) after symptom onset, respectively. Patients receiving fibrinolysis <2 hours after symptom onset were younger, and more likely to be male and have had a prior myocardial infarction and PCI. Patients who received fibrinolysis ≥2 hours after symptom onset had higher GRACE risk scores (127 vs 122, p=0.004). Baseline characteristics and treatment variables were well balanced between treatment arms within each symptom-to-fibrinolysis time stratum. The efficacy of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary endpoint, death at 30 days, or the composite of death or reinfarction at 30 days, 6 months, or 1 year (Figure). The effect of an early invasive strategy on TIMI major bleeding was also similar between strata. The efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time from symptom onset to fibrinolysis. A routine early invasive strategy is safe and effective even if fibrinolytic is administered shortly (<2 hours) after symptom onset.