Heparin Plus a Glycoprotein IIb/IIIa Inhibitor Versus Bivalirudin Monotherapy and Paclitaxel-Eluting Stents Versus Bare-Metal Stents in Acute Myocardial Infarction (HORIZONS-AMI): Final 3-Year Results From a Multicentre, Randomised Controlled Trial
What are the 3-year outcomes for patients randomly allocated to the different pharmacological and stent-type groups in the HORIZONS-AMI trial?
HORIZONS-AMI was a prospective, open-label, randomized trial undertaken at 123 institutions in 11 countries. Patients ages 18 years or older were eligible for enrollment if they had ST-segment elevation myocardial infarction (STEMI), presented within 12 hours after onset of symptoms, and were undergoing primary percutaneous coronary intervention (PCI). By use of a computerized interactive voice response system, investigators randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomization; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare-metal stent (stent randomization; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). The authors produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat.
Compared with 1,802 patients allocated to receive heparin plus a GPI, 1,800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5.9% vs. 7.7%, difference −1.9% [−3.5 to −0.2], hazard ratio 0.75 [0.58–0.97]; p = 0.03), cardiac mortality (2.9% vs. 5.1%, −2.2% [−3.5 to −0.9], 0.56 [0.40–0.80]; p = 0.001), reinfarction (6.2% vs. 8.2%, −1.9% [−3.7 to −0.2], 0.76 [0.59–0.99]; p = 0.04), and major bleeding not related to bypass graft surgery (6.9% vs. 10.5%, −3.6% [−5.5 to −1.7], 0.64 [0.51–0.80]; p = 0.0001) at 3 years, with no significant differences in ischemia-driven target vessel revascularization, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2,257 patients who received a paclitaxel-eluting stent had lower rates of ischemia-driven target lesion revascularization (9.4% vs. 15.1%, −5.7% [−8.6 to −2.7], 0.60 [0.48–0.76]; p < 0.0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke, or stent thrombosis. Stent thrombosis was high (≥4.5%) in both groups.
The authors concluded that the effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary PCI.
The 3-year report from the HORIZONS-AMI trial suggests that after primary PCI in patients with STEMI, initial treatment with bivalirudin alone results in a significant reduction in non–coronary artery bypass grafting-related major bleeding, reinfarction, and all-cause mortality compared with treatment with heparin plus a GPI. Furthermore, implantation of a paclitaxel-eluting stent can result in a significant reduction in ischemia-driven target lesion revascularization compared with implantation of a bare-metal stent, with rates of all-cause and cardiac mortality, reinfarction, and stent thrombosis that did not differ between groups. The increasing difference in mortality over time between bivalirudin and heparin plus a GP IIb/IIIa inhibitor was striking, and supports the use of bivalirudin as the preferred antithrombotic agent for primary PCI. This large study also reaffirms the safety and efficacy of drug-eluting stents for primary PCI. The rate of stent thrombosis was notably high (~5% at 3 years) with both stent types and needs further study.
Keywords: Paclitaxel, Myocardial Infarction, Intention, Drug-Eluting Stents, Heparin, Coronary Artery Bypass, Hirudins, Stents, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex
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