HEAT-PPCI - How effective are antithrombotic therapies in primary percutaneous coronary intervention: A randomised controlled trial comparing unfractionated heparin and bivalirudin
Creators: name: Shahzad, Adeel
Publisher: name: Imperial College London
Year: 2018

description: Aims: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We performed a trial to compare antithrombotic therapy with bivalirudin or unfractionated heparin (heparin) during PPCI. We also planned pre-specified secondary analyses comparing antiplatelet and antithrombotic effects of bivalirudin and heparin and the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events. Methods: This was a single centre, open label, randomised controlled trial. We used a strategy of delayed consent and consecutive patients were included without initial discussion. Before angiography, patients were randomised to either heparin (70 units/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg/hour). Patients were followed for 28 days. The primary outcome measure was a composite of all-cause mortality, cerebrovascular accident (CVA), reinfarction or unplanned target lesion revascularization (TLR). The primary safety outcome was the rate of major bleeding - type 3-5 as per the Bleeding Academic Research Consortium (BARC) definitions. For patients recruited during working hours, we assessed ADP-induced platelet aggregation at the end of the index procedure and at 24 hours. The effects of P2Y12 inhibitors on the primary and safety outcomes were assessed in all patients. Findings: A total of 1829 patients were randomised (100% of eligible patients and 97% of all PPCI-related procedures). A PCI procedure was performed in 82% of cases. The rate of GP IIb/IIIa inhibitor use was: bivalirudin 13·5%, heparin 15·5%. The primary efficacy outcome measure was observed more frequently in patients treated with bivalirudin (8·7% v 5·7%, absolute risk difference = 3%; relative risk [RR] 1·52, 95% confidence interval [CI], 1·09 to 2·13; P=0·01). All elements of the composite favoured heparin but the difference was mainly related to an increased incidence of stent thrombosis with bivalirudin (3·4% v 0·9%, RR 3·91, 95% CI 1·61 to 9·52; P=0·001), causing reinfarction events. There was no difference in major bleeding (3·5% bivalirudin v 3·1% heparin; RR 1·15, CI 0·70 to 1·89; P=0·59). There were no significant differences between patients who received heparin and bivalirudin in AA- and ADP-mediated platelet aggregation at the end of procedure (EOP) or at 24 hours. Multiple Electrode Aggregometry (MEA) data from 469 patients for antiplatelet therapy showed that prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40U (23, 78) when compared against ticagrelor 75U (41, 100.75) or clopidogrel 79U (56, 96); p &lt; 0.001. After adjustment of baseline characteristics, there were no significant differences in the rates of MACE or major bleeding between the antiplatelet therapies. Conclusions: Use of heparin, rather than bivalirudin, is associated with a reduced rate of major adverse ischaemic events, with no increase in bleeding complications. More systematic use of heparin offers the potential for a substantial reduction in drug cost. There were no significant differences between heparin and bivalirudin with respect to AA- or ADP-mediated platelet aggregation. No significant differences were found between the antiplatelet therapies for clinical outcomes.