Gregg W Stone, professor of medicine and the director of research and education at the Center for Interventional Vascular Therapy at the Columbia University Medical Center/New York-Presbyterian Hospital and principal investigator of the trial announced on 25 September 2009 two-year follow-up data from the HORIZONS-AMI trial at the 21st annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in San Francisco, US.
Stone told delegates that, at two years initial treatment with bivalirudin alone compared to heparin plus GP IIb/IIIa inhibitor resulted in significant reduction in major bleeding, and significant reduction in reinfarction. There was also significant reduction in cardiac mortality and in all-cause mortality. Regarding the stent arm, he said, “Results from the HORIZONS-AMI trial showed impressive and sustained efficacy benefits at two years for patients treated with Taxus stents when compared to bare metal stents in patients with acute myocardial infarction. The data also showed comparable safety outcomes for the Taxus Express and bare metal stents. This study should continue to inform how decisions are made regarding the use of drug-eluting stents in high-risk acute myocardial infarction patients during the early hours of a heart attack.”
The trial is designed to compare heparin plus glycoprotein (GP) IIb/IIIa inhibitors versus bivalirudin, and to determine the safety and efficacy of paclitaxel-eluting compared to bare metal stenting in patients experiencing an acute myocardial infarction. With 3,006 patients enrolled worldwide, HORIZONS-AMI is the largest randomised trial to compare the use of drug-eluting stents to bare metal stents for myocardial infarction patients. Stone reminded delegates of the HORIZONS-AMI one-year results, which showed that bivalirudin alone compared to heparin plus GP IIb/IIIa inhibitors resulted in comparable rates of myocardial infarction and stent thrombosis, with significantly reduced rates of major bleeding and mortality. The one-year data also revealed that Taxus paclitaxel-eluting stents reduced clinical and angiographic restenosis compared to bare metal stenting. Whether these results were sustained at two-year follow-up had so far not been reported.
The marked reduction in major bleeding that was seen with bivalirudin at one year was maintained at two years, Stone reported, with a 36% reduction in bleeding at two years. There was no difference in the rate of major adverse cardiovascular events between heparin plus GPIIb/IIIa and bivalirudin alone. In cardiac mortality there was a marked (41%) reduction with bivalirudin alone (2.5%) versus heparin plus GPIIb/IIIa (4.2%). For non-cardiac mortality the rates were identical. A new finding, Stone noted, was that at two years, the lower rate of reinfarction seen in the bivalirudin arm at one year was somewhat sustained at two years (5.1%), whereas with heparin plus GPIIb/IIIa the rate of reinfarction continued to grow (6.9% at two years); a 25% reduction with bivalirudin. There was no difference in rates of major adverse cardiac events between the two agents (18.8% vs. 18.7%), and there were comparable rates of stent thrombosis (4.3% vs. 4.6%).
Stone then went on to report the results for the stent arm (Taxus paclitaxel-eluting stent versus Express bare metal stent). After two years of follow-up, the primary efficacy endpoint of ischaemia-driven target lesion revascularisation was 6.8% for patients treated with drug-eluting stents vs. 11.6% for bare metal stents. The primary safety endpoint of major adverse cardiac events at two years was comparable among drug-eluting stents and bare metal stents patients (11% vs. 11.2%, respectively, p=0.90), which is consistent with one-year findings. Individual rates of death, repeat heart attack, stroke and stent thrombosis between the two groups through two years of follow-up were also comparable, even after correction for any measured baseline differences. Adverse events between one and two years showed that all-cause death was lower among drug-eluting stent patients (0.8% vs. 1.8% bare metal stents, p=0.04), ischaemia-driven target lesion revascularisation was lower among drug-eluting stent patients (2.6% vs. 4.7% bare metal stents, p=0.006), and ischaemia-driven target vessel revascularisation showed similar lower rates with drug-eluting stents compared to bare metal stents (3.4% vs. 5.2%, p=0.03).
The trial, sponsored by the Cardiovascular Research Foundation (CRF) with grant support from Boston Scientific and The Medicines Company, The Taxus Express stent and the Express stent are not specifically indicated by the FDA for use in patients with acute myocardial infarction.