Thromb Haemost 2015; 114(05): 933-944
DOI: 10.1160/TH14-12-1066
Review Article
Schattauer GmbH

Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes

Comprehensive network meta-analysis of 42 randomised trials involving 117,353 patients
Eliano Pio Navarese
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Felicita Andreotti
2   Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy
13   Cardiothoracic Department, Heart Hospital, Fondazione Toscana Gabriele Monasterio, Massa, Italy
,
Michalina Kołodziejczak
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
3   Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Volker Schulze
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Georg Wolff
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Sofia Dias
4   University of Bristol, School of Social and Community Medicine, Bristol, UK
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Bimmer Claessen
5   Department of Cardiology, Academisch Medisch Centrum, Universiteit van Amsterdam, Netherlands
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Marc Brouwer
6   Department of Cardiology, UMC St Radboud, Nijmegen, Netherlands
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Giuseppe Tarantini
7   Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy
,
Sabino Iliceto
7   Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy
,
Maximilian Brockmeyer
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Mariusz Kowalewski
8   Department of Cardiology, 10th Military Research Hospital and Polyclinic, Bydgoszcz, Poland
,
Yingfeng Lin
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
John Eikelboom
9   Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Giuseppe Musumeci
10   Azienda Ospedaliera Papa Giovanni XXIII Bergamo, Lombardia, Italy
,
Leong Lee
11   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
,
Gregory Y. H. Lip
11   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
,
Marco Valgimigli
12   Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands
,
Sergio Berti
13   Cardiothoracic Department, Heart Hospital, Fondazione Toscana Gabriele Monasterio, Massa, Italy
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
,
Malte Kelm
1   Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
14   Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network
› Institutsangaben
Financial support: Part of this study was supported by the Collaborative Research Center 1116 Masterswitches in Myocardial Ischemia, funded by the German Research Council (Deutsche Forschungsgemeinschaft).
Weitere Informationen

Publikationsverlauf

Received: 20. Dezember 2014

Accepted after major revision: 19. Mai 2015

Publikationsdatum:
06. Dezember 2017 (online)

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Summary

International guidelines differ in strengths of recommendation for anticoagulation strategies in acute coronary syndromes (ACS). We performed a comprehensive network meta-analysis (NMA) of randomised controlled trials (RCTs) to investigate the comparative efficacy and safety of parenteral anticoagulants in ACS. MEDLINE, Cochrane, EM-BASE, Google Scholar, major cardiology websites, and abstracts/presentations were searched. Six treatments were identified: 1) unfractionated heparin (UFH) + glycoprotein IIb/IIIa inhibitor (GPI) [UFH+GPI], 2) UFH±GPI, 3) bivalirudin, 4) low-molecular-weight heparins (LMWHs), 5) otamixaban, and 6) fondaparinux. Prespecified outcomes (death, myocardial infarction [MI], revascularisation, major bleeding [MB], minor bleeding, and stent thrombosis [ST]) were evaluated up to 30 days. Forty-two RCTs involving 117,353 patients were included. No significant differences in mortality rates were found among strategies. Compared to UFH+GPI, bivalirudin reduced the odds of MB but increased the odds of ST and MI. LMWHs vs bivalirudin reduced MI risk at the price of MB excess. UFH±GPI significantly increased the odds of MI vs LMWHs, of ST vs UFH+GPI, and of MB vs bivalirudin. Reduced ST risk with otamixaban vs UFH±GPI and vs bivalirudin was offset by a marked 2.5- to four-fold MB excess. Fondaparinux showed an intermediate profile. Results for ST-segment elevation MI were consistent with the overall findings. Early anticoagulant strategies for ACS differ in efficacy and safety, with UFH+GPI and LMWHs reducing ischaemic but increasing bleeding risk, and bivalirudin reducing MB but increases MI and ST. The findings support individualised therapy based on patients´ bleeding and ischaemic risks.

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