This UK single-centre pragmatic study (n=1829) sought to compare the relative safety and efficacy of heparin (70U/kg) and bivalirudin in modern primary PCI (PPCI) practice, where GP IIb/IIIa inhibitors were reserved for selective bailout use (previous studies have involved asymmetrical use of these agents, more commonly in those receiving heparin). All patients presenting at the PPCI service were considered for inclusion, with randomisation prior to entry into the cath lab, and only few exclusion criteria were applied (which applied to only 3% of those recruited). Delayed consent was used; the data for those who died before consent could be given (1%) was included as agreed by the Confidentiality Advisory Group. All patients received dual antiplatelet therapy prior to the procedure as per routine practice.
The primary endpoint was the proportion of patients having at least one major cardiac adverse event (MACE; composite of all-cause mortality, cerebrovascular accident, reinfarction or unplanned target lesion revascularisation) at 28 days. This was 8.7% for the bivalirudin group and 5.7% for the heparin group (absolute difference in risk of 3.0%; p=0.01); the advantage of heparin was primarily driven by an increase in revascularisation in the bivalirudin group, and most of these events were related to stent thrombosis. The primary safety outcome of major bleeding by 28 days was similar for both groups (3.5% for bivalirudin and 3.1% for heparin; p=0.59). Rates of minor bleeding also did not differ between groups.
The authors note that this study had a real-world, unselected population, typical for UK practice. Most evidence in PPCI has compared bivalirudin monotherapy with a combination of heparin plus GP IIb/IIIa inhibitors, and previously observed advantages of bivalirudin were related to reduced bleeding complications. The unselected use of GP IIb/IIIa inhibitors in PPCI is however no longer part of routine practice, due to the use of more effective oral antiplatelet regimens.
Bivalirudin with selective GP IIa/IIIb use has emerged as first-line therapy in this setting; this study however suggests heparin confers benefit in terms of lower incidence of MACE. Use of heparin instead of bivalirudin would be associated with large cost savings.
The current NICE pathway on STEMI states that bivalirudin in combination with aspirin and clopidogrel is recommended for the treatment of adults with STEMI undergoing primary PCI [its license specifies administration with aspirin and clopidogrel]. Unfractionated heparin or low molecular weight heparin should be offered to people with acute STEMI who are undergoing primary PCI and have been treated with prasugrel or ticagrelor.