MedWire News: The previously reported benefits of anticoagulation with bivalirudin alone over heparin and routine glycoprotein (GP)IIb/IIIa inhibitors in primary percutaneous coronary intervention (PCI) extend to ST-elevation myocardial infarction (STEMI) patients, according to HORIZONS-AMI investigators.
The data, initially unveiled at the Transcatheter Cardiovascular Therapeutics 2007 meeting last October, are published in full in this week's New England Journal of Medicine. The authors report that bivalirudin improved 30-day event-free survival compared with heparin and GPIIb/IIIa inhibitors, owing to a reduction in major bleeding.
Previous studies have demonstrated that bivalirudin reduces major and minor bleeding in comparison with heparin plus GP IIb/IIIa inhibitors, with similar efficacy in suppressing ischemia, in angina and non-ST-elevation acute coronary syndrome patients. But, explain Gregg Stone (Columbia University Medical Center, New York, USA) and colleagues, it remained unclear whether any benefit with bivalirudin would also apply in high-risk STEMI patients.
The researchers therefore conducted the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute MI) trial, including 3602 STEMI patients undergoing PCI.
At 30 days, the half of patients who were randomly assigned to receive bivalirudin alone had a significantly reduced rate of net clinical adverse events compared with the other half assigned to heparin plus a GPIIb/IIIa inhibitor, at 9.2% versus 12.1%, giving a 24% reduction in the relative risk (RR; p=0.005).
This was due to a lower rate of major bleeding with bivalirudin compared with heparin plus GPIIb/IIIa inhibitors (4.9% vs 8.3%, RR=0.60; p<0.001), as rates of major adverse clinical events were similar (5.4% vs 5.5%, RR=0.99).
Bivalirudin treatment was also associated with lower 30-day rates of cardiac and all-cause deaths compared with heparin plus GP IIb/IIIa inhibitors, at 1.8% versus 2.9%, (RR=0.62, p=0.03) and 2.1% versus 3.1% (RR=0.66, p=0.047), respectively.
Among the 3124 patients who were successfully implanted with stents, there was an increased acute stent thrombosis risk in the bivalirudin group compared with the heparin plus GPIIb/IIIa inhibitors group, at 1.3% versus 0.3% in the first 24 hours (p<0.001). However, the overall stent thrombosis rate did not differ between groups at 30 days, at corresponding rates of 2.5% and 1.9%, respectively (p=nonsignificant).
Writing in a related editorial, David Morrow (Brigham and Women's Hospital, Harvard Medical School, Boston, USA) cautioned that the "intriguing finding" that bivalirudin may lower mortality is only a secondary finding of the trial, with broad confidence intervals. He noted that evidence to support the authors' suggestion that this was due to reduced bleeding is mixed, not least because there may well be residual confounding by clinical features associated with poor survival.
He concluded that the trial has "substantially increased the experience with bivalirudin in a new setting," and that the findings indicate "bivalirudin warrants consideration among the alternatives for ancillary antithrombotic therapy in patients undergoing primary PCI."
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