EUROMAX: Bivalirudin May Hold Key to Solving Problem of Early ST After Primary PCI

WASHINGTON, DC—Clinicians continue to search for a pharmacologic strategy to combat acute stent thrombosis that occurs shortly after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). One such strategy may be extended bivalirudin at the dose given during PCI, according to a subanalysis of the EUROMAX trial presented March 29, 2014, at the American College of Cardiology/i2 Scientific Session.

In the main EUROMAX trial, researchers at 65 European centers randomized 2,218 STEMI patients who were being transported 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 the bivalirudin strategy reduces short-term death and major non-CABG bleeding. However, there was a low, persistent rate of acute stent thrombosis.

For the new study, Peter Clemmensen, MD, of Rigshospitalet (Copenhagen, Denmark), and colleagues looked at 2,198 STEMI patients in EUROMAX. Patients received a number of post-PCI strategies including:

• Reduced-dose bivalirudin infusion (0.25 mk/kg/hr)
• Prolonged bivalirudin PCI dose (1.75 mg/kg/hr)
• Heparins plus GPIs

The overall rate of acute stent thrombosis was 0.6% and was higher with bivalirudin than heparins with or without GPIs (1.1% vs 0.2%; P = 0.007). The median time to acute stent thrombosis was 2.3 hours.

On multivariable analysis, presence of hypertension (OR 0.21; P = 0.047) and low-dose bivalirudin (OR 7.7; P = 0.009) were found to be predictors of acute stent thrombosis. The choice of prasugrel or ticagrelor had no impact on acute stent thrombosis.

Acute stent thrombosis was 0.2% in the heparin with or without GPI arm, 1.6% in the low-dose bivalirudin arm, and 0.4% in the extended PCI bivalirudin dose arm. Major bleeding in each of the respective bivalirudin arms was 6.0%, 2.4%, and 2.9% (P < 0.05 for both outcomes vs heparin with or without GPIs).

“This post-hoc analysis from EUROMAX confirms that the risk of acute stent thrombosis is limited to the first few hours (probably within 4) after PCI,” Dr. Clemmensen concluded. "Neither loading with.... prasugrel nor ticagrelor or prolonging the low dose (0.25 mg bivalirudin) postPCI was protective.”

In contrast, he continued, “a prolonged bivalirudin infusion at the PCI dose was not associated with a higher risk of acute stent thrombosis compared with unfractionated heparin with or without GPIs and without an increase in the risk of bleeding. Maintaining the bivalirudin infusion at the PCI dose for the first few hours after the end of the procedure is safe and may protect from acute stent thrombosis. However, this strategy needs to be confirmed in larger trials or registries to give us comfort as PCI operators.”

Findings Affect Practice

According to session comoderator Dominick J. Angiolillo, MD, PhD, of the University of Florida College of Medicine (Jacksonville, FL), the study confirms what many operators are currently doing in the field, including himself. Dr. Angiolillo also had a more practical question for Dr. Clemmensen: “How has EUROMAX changed your practice?”

After seeing these results, Dr. Clemmensen responded, we started giving “almost religiously 4 hours after the procedure a full dose [of bivalirudin] and then [any] P2Y12 inhibitor."

Source:
Clemmensen P. Predictors associated with acute stent thrombosis after primary PCI: Insights from the Euromax trial. Presented at the American College of Cardiology (ACC) i2 annual scientific Session; March 29, 2014; Washington, DC.

Disclosures:

• EUROMAX was sponsored by The Medicines Company
• Dr. Clemmensen reports relationships with Abbot, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli-lilly, Evolva, Fibrex, Janssen, Merck, , Medtronic, Mitsubishi Pharma,, Nycomed, Myogen, Organon, Pfizer, Pharmacia, Regado, Sanofi, Searle, Servier, and The Medicines Company.

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