Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial

Abstract

AimsIn the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention (PCI) compared with heparin and routine glycoprotein IIb/IIIa inhibitors (GPI). It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout.Methods and resultsIn the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction (STEMI) were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or non-CABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin (n = 1089) with those receiving heparins with routine upstream GPI (n = 649) and those receiving heparins only with GPI use restricted to bailout (n = 460). The primary outcome death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67 and 95% CI 0.46–0.97, P = 0.034), and 9.8% with heparins plus bailout GPI (HR 0.52 and 95% CI 0.35–0.75, P = 0.006). Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome (odds ratio 0.53, 95% CI 0.33–0.87) and major bleeding (odds ratio 0.44, 95% CI 0.24–0.82) compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin (1.6 vs. 0.6 vs. 0.4%, P = 0.09 and 0.09).ConclusionBivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.

Access and Non–Access Site Bleeding After Percutaneous Coronary Intervention and Risk of Subsequent Mortality and Major Adverse Cardiovascular Events

“…40 Similarly, anticoagulant choice is an important determinant of access and non-access site major bleeding complications. Changes in anticoagulant practice from heparin and glycoprotein IIb/IIIa regimes to bivalirudin have been demonstrated to be associated with reductions in major bleeding and mortality, 41,42 with a recent analysis of the National Cardiovascular Data Registry (NCDR) data set, suggesting that changes in anticoagulation strategies over time contributed to ≈50% of the annual reduction in bleeding observed in acute coronary syndrome and elective PCI 43 with more aggressive anticoagulant regimes associated with significant increases in bleeding complications observed in many of the studies included in this meta-analysis (Table IX in the Data Supplement).…”

ST elevation myocardial infarction

“…[18][19][20][21][22] In HORIZONS-AMI, EUROMAX, BRIGHT and MATRIX, bivalirudin was generally superior to unfractionated heparin in terms of reduced bleeding but was associated with higher rates of acute stent thrombosis in 3 out of the 4 studies. All studies used higher rates of GPI in the comparator heparin arm and some continued the bivalirudin infusion post-PPCI.…”

Impact of Arterial Access Site on Outcomes After Primary Percutaneous Coronary Intervention

“…A recent prespecified analysis from EUROMAX demonstrated that bleeding reductions with bivalirudin were observed even in the setting of low-dose heparin without GPI. 10 In the current prespecified analysis from EUROMAX, we investigated whether the selection of arterial access site had an impact on 30-day outcomes and whether radial access mitigated the bleeding reduction benefit of bivalirudin.…”