How Effective Are Antithrombotic Therapies in Primary PCI - HEAT-PPCI

Description:

The goal of the trial was to evaluate bivalirudin and bailout glycoprotein inhibitor compared with unfractionated heparin and bailout glycoprotein inhibitor among patients undergoing primary percutaneous coronary intervention (PPCI).

Hypothesis:

Bivalirudin will reduce adverse events with excess bleeding.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Patients ≥18 years of age with STEMI undergoing PPCI

    Number of enrollees: 1,829 patients
    Duration of follow-up: 28 days
    Mean patient age: 63 years
    Percentage female: 29%

Exclusions:

  • Active bleeding
  • Intolerance or contraindication to study medication
  • Previous enrollment in this trial
  • Artificial ventilation
  • Reduced level of consciousness

Primary Endpoints:

  • Primary efficacy: all-cause mortality, stroke, MI, unplanned revascularization
  • Primary safety: major bleeding

Drug/Procedures Used:

Patients with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI were randomized to bivalirudin (0.75 mg/kg bolus and 1.75 mg/kg/hour infusion) and bailout abciximab (n = 915) versus unfractionated heparin (70 U/kg bolus) and bailout abciximab (n = 914). Study drug was administered before coronary angiography. Delayed consent was obtained after PPCI.

Concomitant Medications:

Preprocedure use of an ADP antagonist was 99.6% (clopidogrel 12%, prasugrel 27%, and ticagrelor 61%)

Principal Findings:

Overall, 1,829 patients were randomized. The mean age was 63 years, 29% were women, and 13% had diabetes. Radial artery access was used in 80%, thrombectomy was performed in 59%, and a drug-eluting stent was implanted in 80%. The use of abciximab was 13% in the bivalirudin group versus 15% in the heparin group. The median activated clotting time (ACT) was 251 seconds in the bivalirudin group versus 224 seconds in the heparin group.

The primary efficacy outcome of all-cause mortality, stroke, reinfarction, or unplanned revascularization occurred in 8.7% of the bivalirudin group versus 5.7% of the heparin group (p = 0.01).

- Death: 5.1% vs. 4.3%
- Stroke: 1.6% vs. 1.2%
- Reinfarction: 2.7% vs. 0.9%
- Unplanned revascularization: 2.7% vs. 0.7%
- Stent thrombosis: 3.4% vs. 0.9% (p = 0.001)
- Major bleeding: 3.5% vs. 3.1% (p = 0.59), respectively, for bivalirudin vs. heparin

The primary safety outcome of major bleeding occurred in 3.5% of the bivalirudin group vs. 3.1% of the heparin group (p = 0.59).

Interpretation:

Among patients with STEMI undergoing PPCI, with selective use of abciximab (i.e., bailout) and preprocedure dual antiplatelet therapy, the use of bivalirudin was inferior to unfractionated heparin. Bivalirudin was associated with an increase in adverse cardiovascular events, due to an increase in MI/stent thrombosis. There was no major bleeding reduction with bivalirudin, which is often touted as the predominant reason to use this agent; however, catheterization was mostly performed by radial access.

Strengths of this pragmatic trial include enrollment of virtually all patients with STEMI. Also, the dose of heparin was lower than what had been used in some previous trials (100-140 U/kg), which is more consistent with current practice. Although this was a large and well-designed trial, it was conducted from a single center and used open-label design (independent blinded adjudication of outcomes).

References:

Shahzad A, Kemp I, Mars C, et al., on behalf of the HEAT-PPCI trial investigators. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet 2014;Jul 5:[Epub ahead of print].

Editorial: Berger PB, Blankenship JC. Is the heat on HEAT-PPCI appropriate? Lancet 2014;Jul 5:[Epub ahead of print].

Editorial: Shaw D. HEAT-PPCI sheds light on consent in pragmatic trials. Lancet 2014;Jul 5:[Epub ahead of print].

Presented by Dr. Adeel Shahzad at the American College of Cardiology Scientific Session, Washington, DC, March 31, 2014.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Heparin, Immunoglobulin Fab Fragments, Hirudins, Percutaneous Coronary Intervention, Coronary Angiography, Thrombectomy, Thrombosis, Catheterization, Recombinant Proteins, Peptide Fragments, Diabetes Mellitus


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