Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology

Behnood Bikdeli; Thomas McAndrew; Aaron Crowley; Shmuel Chen; Ghazaleh Mehdipoor; Björn Redfors; Yangbo Liu; Zixuan Zhang; Mengdan Liu; Yiran Zhang; Dominic P. Francese; David Erlinge; Stefan K. James; Yaling Han; Yi Li; Adnan Kastrati; Stefanie Schüpke; Rod H. Stables; Adeel Shahzad; Philippe Gabriel Steg; Patrick Goldstein; Enrico Frigoli; Roxana Mehran; Marco Valgimigli; Gregg W. Stone

doi:10.1055/s-0039-1700872

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2020; 120(02): 348-362
DOI: 10.1055/s-0039-1700872

Trial Protocol Design Paper

Georg Thieme Verlag KG Stuttgart · New York

Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology

Behnood Bikdeli

¹Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, United States

²Center for Outcomes Research & Evaluation, Yale School of Medicine, Yale University, New Haven, Connecticut, United States

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Thomas McAndrew

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Aaron Crowley

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Shmuel Chen

¹Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, United States

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Ghazaleh Mehdipoor

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Björn Redfors

¹Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, United States

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

⁴Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden

,

Yangbo Liu

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Zixuan Zhang

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Mengdan Liu

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Yiran Zhang

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Dominic P. Francese

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

David Erlinge

⁵Department of Cardiology, Lund University, Lund, Sweden

,

Stefan K. James

⁶Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden

,

Yaling Han

⁷Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China

,

Yi Li

⁷Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China

,

Adnan Kastrati

⁸Department of Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany

,

Stefanie Schüpke

⁸Department of Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany

,

Rod H. Stables

⁹Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

¹⁰University of Liverpool, Liverpool, United Kingdom

,

Adeel Shahzad

⁹Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

,

Philippe Gabriel Steg

¹¹Hôpital Bichat, Paris, France

¹²Imperial College, Royal Brompton Hospital, London, United Kingdom

,

Patrick Goldstein

¹³Lille University Hospital, Lille, France

,

Enrico Frigoli

¹⁴Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland

,

Roxana Mehran

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

¹⁵The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States

,

Marco Valgimigli

¹⁴Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland

,

Gregg W. Stone

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

¹⁵The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States

› Institutsangaben

Abstract

Background Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed.

Objective To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin.

Methods We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin.

Results From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin).

Conclusion We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.

Keywords

bivalirudin - heparin - pooled analysis - percutaneous coronary intervention - acute myocardial infarction

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