Bivalirudin vs Heparins With Bailout GP IIb/IIIa Inhibitors
Bivalirudin vs Heparins With Bailout GP IIb/IIIa Inhibitors
Aims In 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 results In 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).
Conclusion Bivalirudin, 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.
According to the current guidelines of the European Society of Cardiology (ESC) for patients with acute myocardial infarction with persistent ST-segment elevation, intravenous anticoagulation is recommended in all patients undergoing primary percutaneous coronary intervention (PCI). Unfractionated heparin (UFH) has traditionally been used in the catheterization laboratory as the anticoagulant of choice during primary PCI to prevent thrombosis and ischaemic events. However, UFH has several pharmacological limitations including a high intra- and inter-individual variability. Bivalirudin is a thrombin-specific anticoagulant, which has the ability to inactivate both free and fibrin-bound thrombin. In several randomized clinical trials, bivalirudin has demonstrated efficacy and safety in patients undergoing PCI. In the HORIZONS trial, bivalirudin reduced the primary combined endpoint including death, myocardial infarction and bleeding complications compared to heparin plus routine glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing primary PCI. Moreover, cardiovascular mortality was reduced after 30 days and at 3-year follow-up. However, the use of GPI is not always routine in clinical practice anymore and might have contributed to the increase in bleeding complications seen in the control arm. In the EUROMAX trial, the use of GPI was not mandated, but was left to the standard practice of participating centres. This provided the opportunity to compare bivalirudin to heparins without planned use of GPI.
Abstract and Introduction
Abstract
Aims In 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 results In 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).
Conclusion Bivalirudin, 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.
Introduction
According to the current guidelines of the European Society of Cardiology (ESC) for patients with acute myocardial infarction with persistent ST-segment elevation, intravenous anticoagulation is recommended in all patients undergoing primary percutaneous coronary intervention (PCI). Unfractionated heparin (UFH) has traditionally been used in the catheterization laboratory as the anticoagulant of choice during primary PCI to prevent thrombosis and ischaemic events. However, UFH has several pharmacological limitations including a high intra- and inter-individual variability. Bivalirudin is a thrombin-specific anticoagulant, which has the ability to inactivate both free and fibrin-bound thrombin. In several randomized clinical trials, bivalirudin has demonstrated efficacy and safety in patients undergoing PCI. In the HORIZONS trial, bivalirudin reduced the primary combined endpoint including death, myocardial infarction and bleeding complications compared to heparin plus routine glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing primary PCI. Moreover, cardiovascular mortality was reduced after 30 days and at 3-year follow-up. However, the use of GPI is not always routine in clinical practice anymore and might have contributed to the increase in bleeding complications seen in the control arm. In the EUROMAX trial, the use of GPI was not mandated, but was left to the standard practice of participating centres. This provided the opportunity to compare bivalirudin to heparins without planned use of GPI.