Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial)

Am Heart J. 2016 May:175:36-46. doi: 10.1016/j.ahj.2016.02.007. Epub 2016 Feb 20.

Abstract

Background: The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs.

Methods/design: The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries.

Conclusion: The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Electrocardiography / methods
  • Female
  • Heparin* / administration & dosage
  • Heparin* / adverse effects
  • Hirudins* / administration & dosage
  • Hirudins* / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Non-ST Elevated Myocardial Infarction / diagnosis
  • Non-ST Elevated Myocardial Infarction / drug therapy
  • Outcome and Process Assessment, Health Care
  • Peptide Fragments* / administration & dosage
  • Peptide Fragments* / adverse effects
  • Percutaneous Coronary Intervention* / methods
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Registries
  • ST Elevation Myocardial Infarction* / diagnosis
  • ST Elevation Myocardial Infarction* / drug therapy
  • Treatment Outcome

Substances

  • Anticoagulants
  • Hirudins
  • Peptide Fragments
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • Heparin
  • bivalirudin