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
1  Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, United States
2  Center for Outcomes Research & Evaluation, Yale School of Medicine, Yale University, New Haven, Connecticut, United States
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Thomas McAndrew
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Aaron Crowley
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Shmuel Chen
1  Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, United States
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Ghazaleh Mehdipoor
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Björn Redfors
1  Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, United States
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
4  Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
,
Yangbo Liu
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Zixuan Zhang
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Mengdan Liu
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Yiran Zhang
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Dominic P. Francese
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
David Erlinge
5  Department of Cardiology, Lund University, Lund, Sweden
,
Stefan K. James
6  Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
,
Yaling Han
7  Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
,
Yi Li
7  Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China
,
Adnan Kastrati
8  Department of Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany
,
Stefanie Schüpke
8  Department of Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany
,
Rod H. Stables
9  Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
10  University of Liverpool, Liverpool, United Kingdom
,
Adeel Shahzad
9  Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
,
Philippe Gabriel Steg
11  Hôpital Bichat, Paris, France
12  Imperial College, Royal Brompton Hospital, London, United Kingdom
,
Patrick Goldstein
13  Lille University Hospital, Lille, France
,
Enrico Frigoli
14  Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Roxana Mehran
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
15  The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
,
Marco Valgimigli
14  Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Gregg W. Stone
3  Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
15  The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
› Author Affiliations
Funding This project was partially supported by a research grant from The Medicines Company (Parsippany, New Jersey, United States) to the Cardiovascular Research Foundation (New York, New York, United States) and by the Cardiovascular Research Foundation.
Further Information

Publication History

29 June 2019

12 September 2019

Publication Date:
09 December 2019 (online)

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.