Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes

Eliano Pio Navarese; Felicita Andreotti; Michalina Kołodziejczak; Volker Schulze; Georg Wolff; Sofia Dias; Bimmer Claessen; Marc Brouwer; Giuseppe Tarantini; Sabino Iliceto; Maximilian Brockmeyer; Mariusz Kowalewski; Yingfeng Lin; John Eikelboom; Giuseppe Musumeci; Leong Lee; Gregory Y. H. Lip; Marco Valgimigli; Sergio Berti; Malte Kelm

doi:10.1160/TH14-12-1066

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Felicita Andreotti

²Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy

¹³Cardiothoracic Department, Heart Hospital, Fondazione Toscana Gabriele Monasterio, Massa, Italy

,

Michalina Kołodziejczak

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

³Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Volker Schulze

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Georg Wolff

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Sofia Dias

⁴University of Bristol, School of Social and Community Medicine, Bristol, UK

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Bimmer Claessen

⁵Department of Cardiology, Academisch Medisch Centrum, Universiteit van Amsterdam, Netherlands

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Marc Brouwer

⁶Department of Cardiology, UMC St Radboud, Nijmegen, Netherlands

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Giuseppe Tarantini

⁷Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy

,

Sabino Iliceto

⁷Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy

,

Maximilian Brockmeyer

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Mariusz Kowalewski

⁸Department of Cardiology, 10th Military Research Hospital and Polyclinic, Bydgoszcz, Poland

,

Yingfeng Lin

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

John Eikelboom

⁹Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

,

Giuseppe Musumeci

¹⁰Azienda Ospedaliera Papa Giovanni XXIII Bergamo, Lombardia, Italy

,

Leong Lee

¹¹University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK

,

Gregory Y. H. Lip

¹¹University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK

,

Marco Valgimigli

¹²Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands

,

Sergio Berti

¹³Cardiothoracic Department, Heart Hospital, Fondazione Toscana Gabriele Monasterio, Massa, Italy

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

,

Malte Kelm

¹Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany

¹⁴Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-Medicine Research Network

› Institutsangaben

Abstract

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.

Keywords

Acute coronary syndrome - parenteral anticoagulant - network meta-analysis

Volltext

Referenzen

References
1 Amsterdam EA, Wenger NK, Brindis RG. et al. 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 64: e139-e228.
2 American College of Emergency, Physicians Society for Cardiovascular and Angiography Interventions. O'Gara PT, Kushner FG, Ascheim DD. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: e78-140.
3 Hamm CW, Bassand JP, Agewall S. et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2999-3054.
4 Task Force on the management of S. T. segment elevation acute myocardial infarction of the European Society of Cardiology. Steg PG, James SK, Atar D. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619.
5 Mehta SR, Granger CB, Eikelboom JW. et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol 2007; 50: 1742-1751.
6 Stone G, McLaurin B, Cox D. et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355: 2203-2216.
7 Stone G, Witzenbichler B, Guagliumi G. et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218-2230.
8 Yusuf S, Mehta S, Chrolavicius S. et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. J Am Med Assoc 2006; 295: 1519-1530.
9 Dias S, Welton NJ, Sutton AJ. et al. Evidence synthesis for decision making 1: introduction. Med Decision Making 2013; 33: 597-606.
10 Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 2004; 23: 3105-3124.
11 Navarese EP, Tandjung K, Claessen B. et al. Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta-analysis. Br Med J 2013; 347: f6530.
12 Liberati A, Altman DG, Tetzlaff J. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009; 151: W65-94.
13 Higgins J, Green D. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. Cochrane Collaboration 2011 http://www.cochrane-handbook.org
14 Cutlip DE, Windecker S, Mehran R. et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007; 115: 2344-2351.
15 Dias S, Sutton AJ, Ades AE. et al. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decision Making 2013; 33: 607-617.
16 Welton NJ, Sutton AJ, Cooper NJ. et al. Evidence synthesis for decision making in healthcare. 2012. New York: Wiley.;
17 Dias S, Welton N, Caldwell D. et al. Checking consistency in mixed treatment comparison meta-analysis. Stat Med 2010; 29: 932-944.
18 Navarese EP, De Luca G, Castriota F. et al. Low-molecular-weight heparins vs. unfractionated heparin in the setting of percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis. J Thromb Haemost 2011; 9: 1902-1915.
19 Murphy SA, Gibson CM, Morrow DA. et al. Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J 2007; 28: 2077-2086.
20 Shahzad A, Kemp I, Mars C. et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014 Epub ahead of print.
21 Montalescot G, Zeymer U, Silvain J. et al. Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial. Lancet 2011; 378: 693-703.
22 Navarese EP, Schulze V, Andreotti F. et al. Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin with or without routine glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndrome. JACC Cardiovasc Interv 2015; 8: 201-213.
23 Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet 2014; 384: 599-606.
24 Steg PG, Huber K, Andreotti F. et al. Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2011; 32: 1854-1864.
25 Navarese EP, Andreotti F, Schulze V. et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. Br Med J. 2015 Epub ahead of print.

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