EUROMAX Subanalysis: Bivalirudin Bests Heparin Regardless of GPI Use in STEMI

PARIS, France—In patients with ST-segment myocardial infarction (STEMI) being transported for primary percutaneous coronary intervention (PCI), upstream bivalirudin lowers mortality or major bleeding compared with heparin, an advantage that is consistent with or without additional use of glycoprotein IIb/IIIa inhibitors (GPIs). The findings, from a subanalysis of the EUROMAX trial, were presented Wednesday, May 21, 2014, at EuroPCR.

In the main EUROMAX trial, researchers at 65 European centers randomized 2,218 STEMI patients transferred for primary PCI to bivalirudin (0.75 mg/kg bolus followed by 1.75 mg/kg/h infusion) or unfractionated heparin or enoxaparin (standard practice) with optional glycoprotein IIb/IIIa inhibitors (GPIs). They found that upstream bivalirudin reduces short-term death and major non-CABG bleeding. However, there was a low, persistent rate of acute stent thrombosis.

For the new study, Uwe Zeymer, MD, of Klinikum Ludwigshafen (Ludwigshafen, Germany), and colleagues looked at 2,198 STEMI patients in EUROMAX to determine the influence of bailout GPIs. Patients received a number of strategies including:

• Bivalirudin with routine (n = 42) or no GPI use (n = 1,047; including 83 who received bailout GPIs)
• Heparin plus routine (n = 649) or no GPI use (n = 460; including 117 who received bailout GPIs)

Clear Safety Advantage with Bivalirudin

At 30 days, the primary endpoint of death or major bleeding was lower in the bivalirudin arm (5.1%) than in the heparin arm with either routine (7.4%; P = .0425) or bailout GPIs (9.8%; P = .0006; P for overall interaction = .0026). Bivalirudin showed substantial benefit compared with heparin alone in all other clinical outcomes including net adverse clinical events (NACE; death, MI, ischemia-driven revascularization, stroke, or major bleed; table 1).

Table 1. Outcomes at 30 Days: Bivalirudin vs Heparin Alone

 
Multivariate analysis confirmed these results, once again showing lower likelihood of the primary endpoint (adjusted OR 0.53; 95% CI 0.33-0.87) and major bleeding (adjusted OR 0.44; 95% CI 0.24-0.82) with bivalirudin vs heparin alone.

Heparin, with or without GPI use, showed a trend toward lower rates of stent thrombosis than bivalirudin (0.6% vs 0.4% vs 1.6%; P = .09 for each).

“It seems the advantage of bivalirudin compared to heparin is observed regardless of the use of glycoprotein IIb/IIIa inhibitors,” Dr. Zeymer said.

However, because the use of GPIs was left to the discretion of investigators, he explained, “the equilibrium of randomization in baseline characteristics is potentially lost. Therefore, these results should be considered as hypothesis-generating rather than definitive.”

In response to panel questions about the trial compared with HEAT PPCI, Dr. Zeymer said the results of the subanalysis “put some heat” on the negative findings of the trial presented in March at 2014 American College of Cardiology/i2 Scientific Session. “It’s problematic to [apply] the results of a single-center trial [to] a general population,” he observed. “I’m not sure [their findings] are enough to oppose these results from a multicenter trial.”

Study Details

About half of all patients had single-vessel disease, and radial access was more often used when patients were treated with heparin plus routine GPI vs heparin alone. Additionally, about half of patients received DES, and one-third underwent thrombectomy.

 

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Source:
Zeymer U, van’t Hof A, Adgey J, et al. Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial. Eur Heart J. 2014;Epub ahead of print.

 

 

Related Stories:

• Bivalirudin Safer Than Heparin Alone in ‘Real-World’ PCI Patients Without STEMI
• HEAT PPCI: Results Favoring Heparin over Bivalirudin Raise Scientific, Ethical Issues
• Bivalirudin Shows Advantage Over GPIs—But Not Heparin Alone—in STEMI Patients