Which antithrombotic to use during PCI?

With .2 million percutaneous coronary intervention (PCI) procedures performed worldwide annually, the optimal choice of antithrombotic therapy during PCI is of critical importance. There are three main choices for antithrombotic therapy during PCI: (i) heparin alone: (ii) heparin þ glycoprotein (GP) IIb IIIa inhibitor; or (iii) bivalirudin. The use of heparin during PCI is based upon a clinical rationale that PCI is intensively thrombogenic and an anticoagulant would be essential to avoid high rates of thrombotic occlusion of the coronary artery. As the only intravenous anticoagulant available a few decades ago, heparin quickly became standard practice and so until very recently there have been no trials comparing heparin vs. placebo. A recent placebo-controlled trial of heparin (70– 100 U/kg, n 1⁄4 700) in patients with chronic coronary artery disease undergoing elective PCI and receiving dual antiplatelet therapy demonstrated increased overall bleeding (rates of 1.7% heparin vs. 0% placebo, P 1⁄4 0.048) with no difference in major bleeding (0 vs. 0) with heparin and no significant difference in the composite of death, myocardial infarction (MI), or urgent lesion revascularization [3.7% heparin vs. 2.0% placebo, odds ratio (OR) 1.92; 95% confidence interval (CI) 0.76–4.88, P 1⁄4 0.17]. Further trials of the value of heparin are needed in elective PCI, and at the minimum suggest that lower doses of heparin may be just as effective with less bleeding compared with standard or high dose heparin during PCI. In a large number of trials, GP IIb IIIa inhibitors have been evaluated vs. placebo in patients receiving heparin and aspirin undergoing PCI. A meta-analysis of 21 trials (n 1⁄4 23 941) comparing heparin þ GP IIb IIIa inhibitor vs. heparin alone showed that GP IIb IIIa inhibitors reduced death at 30 days (0.8% vs. 1.2%, OR 0.72; 95% CI 0.56–0.94), reduced MI events (4.5% vs. 6.5%, OR 0.63; 95% CI 0.54–0.74), but there was a trend for increased major bleeding (4.2% vs. 2.9%, OR 1.29; 95% CI 0.98–1.68) and thrombocytopenia (2.5% vs. 1.7%, OR 1.41; 95% CI 1.10–1.81) (Figure 1). However, many of the studies included did not recommend the use of thienopyridines, and so many have questioned the applicability to current practice. Specifically, the ISAR REACT (n 1⁄4 2159) study demonstrated that patients undergoing elective PCI pre-treated with 600 mg of clopidogrel, heparin (140 U/kg) vs. heparin (70 U/kg) þ abciximab had similar ischaemic outcomes and bleeding. In contrast, the ISAR REACT 2 (n 1⁄4 2022) study demonstrated in patients with acute coronary syndromes (ACS) undergoing PCI pre-treated with 600 mg of clopidogrel that heparin (70 U/kg) þ abciximab vs. heparin monotherapy (140 U/ kg) reduced death or MI [relative risk (RR) 0.75; 95% CI 0.57– 0.97] without increasing major bleeding (RR 1.00; 95% CI 0.50– 2.08). The benefit was mainly observed in patients with an elevated troponin (18.3% vs. 13.1%, RR 0.71; 95% CI 0.54–0.95) and not in those without an elevation (4.6% vs. 4.6%, RR 0.99; 95% CI 0.56– 1.76), and this was the rationale for the inclusion of only biomarker-negative patients in the subsequent ISAR REACT 3 trial. These trials support the concept that GP IIb IIIa inhibitors may be less likely to be beneficial in patients undergoing elective PCI or in troponin-negative ACS patients already receiving aspirin, high doses of clopidogrel, and heparin. The third option for an antithrombotic during PCI is bivalirudin which was specifically tested in the ISAR REACT 3 trial. This trial randomized 4570 biomarker-negative patients undergoing PCI pretreated with 600 mg of clopidogrel to (i) bivalirudin monotherapy or (ii) heparin monotherapy (140 U/kg). The initial publication reported that compared with heparin, bivalirudin led to a 44% reduction in major bleeding (3.1% vs. 4.6%, RR 0.66; 95% CI 0.49–0.90), with no difference in net clinical benefit (death, MI, urgent target vessel revascularization, or major bleeding; 8.3% vs. 8.7%, RR 0.94; 95% CI 0.77–1.15). The follow-up at 1 year demonstrates no difference in the composite of death, MI, or target vessel revascularization (17.1% vs. 17.5%, RR 0.98; 95% CI 0.86–1.13) or of death or MI (7.7% vs. 6.7%, RR 1.15; 95% CI