News:Angiomax Monotherapy Associated with Reduced Net Adverse Clinical Events, Major Bleeding and Cardiac‐Related Death Compared to Heparin Plus a Glycoprotein IIb/IIIa Inhibition in Primary PCI: Results of HORIZONS AMI

C. Michael Gibson, M.S., M.D. October 24, 2007

The HORIZONS AMI trial was a prospective, single‐blind (the investigators were not blinded), randomized, multi‐center study in more than 3,600 patients presenting with ST elevation MI in 11 countries. Patients undergoing angioplasty were randomly assigned to receive either Angiomax with provisional use of GPI or heparin plus GPI. Patients enrolled in the HORIZONS AMI trial also were assigned randomly to receive either TAXUS® drug‐eluting stents or bare‐metal stents.

The two co-primary endpoints of the trial were ACUITY defined major bleeding and net adverse clinical events, a composite of major adverse cardiovascular events (all cause death, reinfarction (Re MI), stroke or ischemic target vessel revascularization) and ACUITY major bleeding at 30 days. The major secondary endpoint was major adverse cardiovascular events at 30 days. The statistical analysis was performed on an intent-to-treat basis.

43% of patients sustained an anterior MI. Pre-randomization, UFH was administered to 66% of patients. Although all patients were to undergo primary PCI, 93% of patients actually underwent PCI, 5% received medical therapy, and bypass surgery was performed in 2% of patients. Among patients treated with a GPI, 50% received abciximab and 44% received eptifibatide.

Highlights of the 30 day outcomes were as follows:

all cause death, recurrent MI, ischemia driven target vessel revascularization, stroke and ACUITY major bleeding by 24% (9.2% vs. 12.1%, relative risk [RR] 0.76, 95% CI 0.63-0.92, p = 0.006).
 * Angiomax significantly reduced the incidence of net adverse clinical events, a composite of
 * Angiomax monotherapy was associated with a significant 49% relative risk reduction in the incidence of ACUITY major bleeding compared to UFH + Glycoprotein IIbIIIa inhibition (4.9% vs. 8.3%, p< 0.0001). Likewise, when TIMI major or minor bleeding was used as an endpoint, bivalirudin was associated with a decrease from 9.6% to 5.9%, p <0.001).
 * Angiomax monotherapy was associated with comparable rates of major adverse cardiac events (all cause death, recurrent MI, ischemic driven TVR, stroke) (5.4% vs. 5.5%, p = NS).
 * Angiomax monotherapy was associated with a significant reduction in the incidence of cardiac‐related mortality by 38% (1.8% vs. 2.9%, p= 0.035).
 * At 30 days, there was no significant difference in the risk of stent thrombosis (2.5% risk with bivalirudin vs. 1.9% risk with UFH + GPI IIb/IIIa inhibitor, p = 0.33). However, there was a greater risk of acute stent thrombosis within the first 24 hours associated with bivalirudin administration (1.3% vs. 0.3%, p = 0.0009).

Similar results were observed when the analysis was restricted to patients who in fact underwent primary PCI.

Consistent with prior studies such as REPLACE 2 and ACUITY, the rate of “bailout” or provisional use of glycoprotein IIbIIIa inhibitors was low at 7.2%.

Gregg W. Stone, MD, professor of medicine, Columbia University Medical Center and chairman of the Cardiovascular Research Foundation, which conducted the trial stated that “These data show that the benefits of bivalirudin therapy extend to patients with heart attacks.”

The efficacy and safety of bare metal and drug eluting stents was also assessed. As part of a 2X2 factorial design, the patients were also sub randomized to implantation with either a paclitaxel-eluting stent or a bare metal stent. The results of the stent results are not yet available.

Angiomax is available in Europe as Angiox®.

References

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