Bivalirudin vs. Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy - VALIDATE-SWEDEHEART

Sep 22, 2017
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Swedish Heart-Lung Foundation
Date Presented:
08/27/2017
Date Published:
08/27/2017
Date Updated:
09/22/2017
Original Posted Date:
08/27/2017
References

Contribution To Literature:

The VALIDATE-SWEDEHEART trial showed that bivalirudin was not superior to heparin at preventing adverse events, including major bleeding.

Description:

The goal of the trial was to evaluate bivalirudin compared with unfractionated heparin among patients undergoing coronary revascularization for acute coronary syndromes. Recent trials have failed to find an association between bivalirudin and reduction in major bleeding.

Study Design

  • Randomized
  • Parallel

Patients with acute coronary syndromes undergoing coronary revascularization were randomized to bivalirudin monotherapy (n = 3,004) vs. unfractionated heparin monotherapy (n = 3,002). The majority of patients underwent radial artery access and received a potent ADP receptor antagonist. The dose of bivalirudin was a 0.75 mg/kg bolus, followed by infusion of 1.75 mg/kg/hr. The dose of unfractionated heparin was 70-100 U/kg.

  • Total number of enrollees: 6,006
  • Duration of follow-up: 180 days
  • Mean patient age: 68 years
  • Percentage female: 26%
  • Percentage with diabetes: 16%

Inclusion criteria:

  • Patients with ST-segment elevation myocardial infarction (STEMI) or NSTEMI undergoing coronary revascularization
  • Treatment with a potent ADP receptor antagonist before the start of percutaneous coronary intervention (PCI)

Exclusion criteria:

  • Glycoprotein IIb/IIIa inhibitor given or planned use
  • Bleeding disorder or thrombocytopenia
  • Uncontrolled hypertension
  • Bacterial endocarditis
  • Severe renal insufficiency
  • Receipt of >5000 U heparin before arrival in the catheterization laboratory or >3000 U given during angiography
  • Limited life expectancy

Other salient features/characteristics:

  • Radial access: 90%
  • ADP receptor antagonist: ticagrelor 95%, prasugrel 2%, cangrelor <1%
  • Bailout glycoprotein IIb/IIIa inhibitor: ~2.5%

Principal Findings:

The primary outcome, incidence of all-cause death, MI, or major bleeding at 180 days, occurred in 12.3% of the bivalirudin group vs. 12.8% of the unfractionated heparin group (p = 0.54).

Secondary outcomes:

  • MI at 180 days: 2.0% vs. 2.4% (p = 0.33), respectively, for bivalirudin vs. heparin
  • Definite/probable stent thrombosis: 1.9% vs. 2.0% (p = 0.78), respectively, for bivalirudin vs. heparin
  • Major bleeding: 8.6% vs. 8.6% (p = 0.98), respectively, for bivalirudin vs. heparin

Interpretation:

Among patients with acute coronary syndromes undergoing coronary revascularization, bivalirudin was not effective at preventing death, MI, or major bleeding with unfractionated heparin. Individual outcomes, including major bleeding and stent thrombosis, were also similar between treatment arms.

This large trial is notable for nearly universal radial artery access, potent ADP receptor antagonists, and virtually no glycoprotein IIb/IIIa inhibitors. Recent studies and meta-analyses that controlled for the use of glycoprotein IIb/IIIa inhibitors between treatment arms have also failed to document an association between bivalirudin and reduction in major bleeding. In summary, in contemporary practice, bivalirudin is an acceptable anticoagulant during PCI with expected similar frequency of major bleeding and stent thrombosis compared with heparin.

References:

Erlinge E, Omerovic E, Frobert O, et al. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. N Engl J Med 2017;377:1132-42.

Editorial: Stone GW. Procedural Anticoagulation in Myocardial Infarction. N Engl J Med 2017;377:1198-200.

Presented by Dr. David Erlinge at the European Society of Cardiology Congress, Barcelona, Spain, August 27, 2017.

Keywords: Acute Coronary Syndrome, Adenosine, Anticoagulants, ESC2017, ESC Congress, Hemorrhage, Heparin, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Purinergic P2Y Receptor Antagonists, Stents, Thrombosis


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