Shelley Wood

September 27, 2010

September 27, 2010 (Washington, DC) - In recent years, no TCT meeting has been complete without a presentation from the HORIZONS AMI trial, and TCT 2010 did not disappoint. On the final day of late-breaking clinical-trial sessions, Dr Gregg Stone (Columbia University, New York, NY) presented the three-year results from the trial for both the bivalirudin vs unfractionated heparin (UFH)/GP IIb/IIIa inhibitor randomization, and the drug-eluting stent (DES) vs bare-metal stent randomization.

Dr Gregg Stone

As previously reported by heartwire , HORIZONS AMI randomized 3602 acute MI patients within 12 hours of symptom onset to UFH plus a GP IIb/IIIa inhibitor or bivalirudin (a 1:1 randomization). After angiography, 3006 stent-eligible patients were randomized a second time to either a bare-metal stent or the Taxus paclitaxel-eluting stent (a 3:1 randomization).

Thirty-day, one-year, and two-year results have previously been reported by heartwire . By three years, one of two primary end points for the anticoagulant arm of the study, major bleeding, remained statistically lower in the bivalirudin patients. Both all-cause mortality and cardiac mortality, which were significantly lower in bivalirudin patients at one year, remained lower at three years, with event rates widening slightly over time.

Interestingly, reinfarction rates, which trended higher in the UFH/GP IIb/IIIa group at one year, were significantly different by three years and comprised primarily non Q-wave MI--a finding investigators could not explain. Rates of stent thrombosis were no different between the groups by three years: in fact, in the first 24 hours, definite or probable stent thrombosis rates were significantly higher in the bivalirudin-treated patients, but between 24 hours and three years, stent-thrombosis rates climbed higher in the UFH/GP IIb/IIIa group.

HORIZONS AMI: Major Clinical Outcomes, Bivalirudin vs UFH/GP IIb/IIIa

End point Bivalirudin (%) Heparin+GP IIb/IIIa (%) HR (95% CI) p
Major bleeding 6.9 10.5 0.64 (0.51–0.80) <0.001
All-cause mortality 5.9 7.7 0.75 (0.58–0.97) 0.03
Cardiac mortality 2.9 5.1 0.56 (0.40–0.80) 0.001
Reinfarction 6.2 8.2 0.76 (0.59–0.92) 0.04

In the DES vs bare-metal stent randomization, the reduction in repeat target lesion revascularization seen at one year persisted at three years, both in patients who had undergone angiography and in those who had not. Rates of major adverse cardiac events and of all other clinical end points were no different between the two groups.

In his concluding remarks, Stone emphasized the enduring reduction in major bleeding, reinfarction, cardiac mortality, and all-cause mortality in the bivalirudin-treated patients, as well as the 40% reduction in target lesion revascularization among patients randomized to the paclitaxel stent. He also drew attention to the high rates of stent thrombosis seen in the trial--ranging from 4% to 5% in all study groups--despite the fact that patients tended to maintain the same level of dual antiplatelet therapy.

Better Than We Used to Be?

Dr David Holmes

Dr David Holmes (Mayo Clinic, Rochester, MN), discussing the findings, also zeroed in on this finding, asking whether the solution lay in a better stent scaffold, a better drug, or multiple drugs. "Stent thrombosis again raises its increasingly ugly head in this group of patients. Is it all patients? No. Are we better than we used to be? Yes, but we haven't made a lot of headway in this subset of patients with AMI."

Other interventionalists struggled to understand why, in the bivalirudin/UFH arm of the study, mortality rates seemed to continue to diverge over time.

"I can only speculate," said Stone, "but what we've seen in multiple different studies is that there are prolonged effects of blood transfusions. Blood transfusions induce apoptosis, systemic vasoconstriction, and an inflammatory state. In other studies, those effects last six to 12 months. . . . On the other hand, maybe it is just statistical chance."

This will be the final year of results from HORIZON-AMI, Stone noted, citing "administrative reasons." The trial follow-up is being closed out at three years, two years short of the original trial design.

Stone disclosed being on the advisory board for and receiving honoraria from Boston Scientific and Abbott Vascular and being a consultant for the Medicines Company.