Behnood Bikdeli1,2,3, Thomas McAndrew3, Aaron Crowley3, Shmuel Chen1,3, Ghazaleh Mehdipoor3, Björn Redfors1,3,4, Yangbo Liu3, Zixuan Zhang3, Mengdan Liu3, Yiran Zhang3, Dominic P Francese3, David Erlinge5, Stefan K James6, Yaling Han7, Yi Li7, Adnan Kastrati8, Stefanie Schüpke8, Rod H Stables9,10, Adeel Shahzad9, Philippe Gabriel Steg11,12, Patrick Goldstein13, Enrico Frigoli14, Roxana Mehran3,15, Marco Valgimigli14, Gregg W Stone3,15. 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. 4. Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. 5. Department of Cardiology, Lund University, Lund, Sweden. 6. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. 7. Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China. 8. Department of Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany. 9. Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. 10. University of Liverpool, Liverpool, United Kingdom. 11. Hôpital Bichat, Paris, France. 12. Imperial College, Royal Brompton Hospital, London, United Kingdom. 13. Lille University Hospital, Lille, France. 14. Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland. 15. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States.
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. Georg Thieme Verlag KG Stuttgart · New York.
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. Georg Thieme Verlag KG Stuttgart · New York.
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