HEAT PPCI Trial: Bivalirudin Versus Heparin in Primary Percutaneous Coronary Intervention
Evaluation of: Shahzad A, Kemp I, Mars C et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet pii: S0140-6736(14)60924-7 (2014).
Bivalarudin is an established treatment during primary percutaneous coronary intervention (PPCI) following trials such as HORIZONS-AMI that have suggested that use of bivalirudin improves mortality at 30 days, predominantly by reducing bleeding events. However, the comparator has been heparin with glycoprotein IIB/IIIA inhibitor (GPI; 98% use in HORIZONS-AMI) and this may have stacked the cards in favor of bivalirudin. Perhaps this does not reflect real-world practice, where GPI is used more sparingly.
The single-center HEAT PPCI study assessed 1829 patients presenting with ST-elevation myocardial infarction randomized to bivalirudin or unfractionated heparin with bail-out GPI given in both arms (approximately 15% in both) during PPCI. The primary outcome measure was major adverse cardiac events (MACE) at 28 days with the primary safety outcome measure as major bleeding.
Demographic and procedural characteristics were well matched. The primary outcome measure was reduced with heparin (5.7 vs 8.7%; p = 0.01) as was mortality. The main driver of the MACE difference was a markedly higher rate of stent thrombosis in the bivalirudin group (0.9 vs 3.4%; p = 0.001); there was no significant difference in bleeding rates between groups.
Heparin appeared to be superior to bivalirudin in preventing MACE after PPCI when largely used without GPI and there was no trade off with reduced bleeding in the bivalirudin group. These findings conflict with the results of several other studies such as HORIZONS-AMI, ACUITY, EUROMAX and registries. Concern has been expressed in the trial design (delayed consent) and possible underdosing/abbreviated dosing of bivalirudin. It is possible that bivalirudin with heparin (co-administered in ~60% of HORIZONS-AMI patients in the bivalirudin arm) is optimal to GPI and heparin and further studies are required to resolve these trial differences.