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Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e553 (Published 03 February 2012) Cite this as: BMJ 2012;344:e553
  1. Johanne Silvain, associate professor1,
  2. Farzin Beygui, professor1,
  3. Olivier Barthélémy, senior consultant1,
  4. Charles Pollack Jr, professor2,
  5. Marc Cohen, professor3,
  6. Uwe Zeymer, professor4,
  7. Kurt Huber, professor5,
  8. Patrick Goldstein, professor6,
  9. Guillaume Cayla, associate professor7,
  10. Jean-Philippe Collet, professor1,
  11. Eric Vicaut, professor8,
  12. Gilles Montalescot, professor1
  1. 1Institut de Cardiologie, Bureau 2-236, Centre Hospitalier Universitaire Pitié-Salpêtrière, 47 Boulevard de l’Hopital, 75013 Paris, France
  2. 2Department of Emergency Medicine, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, PA, USA
  3. 3Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ, USA
  4. 4Herzzentrum Klinikum Ludwigshafen, Medizinische Klinik B, Ludwigshafen, Germany
  5. 5Department of Internal Medicine, Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria
  6. 6SAMU, CHRU Lille, France
  7. 7Cardiology Department, Centre Hospitalier Carémeau, Nîmes, France
  8. 8Unité de Recherche Clinique, Lariboisière Hospital, Paris, France
  1. Correspondence to: G Montalescot gilles.montalescot{at}psl.aphp.fr
  • Accepted 19 January 2012

Abstract

Objective To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention.

Design Systematic review and meta-analysis.

Data sources Medline and Cochrane database of systematic reviews, January 1996 to May 2011.

Study selection Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes.

Data extraction Sample size, characteristics, and outcomes, extracted independently and analysed.

Data synthesis 23 trials representing 30 966 patients were identified, including 10 243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11 973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13 943 patients (45.0%) received enoxaparin and 17 023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01).

Conclusion Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction.

Footnotes

  • Contributors: JS, OB, and GM designed the study; acquired, analysed, and interpreted the data; and revised the manuscript. JS, OB, FB, CP, MC, KH, UZ, GC, J-PC, and EV helped implement the study and made critical revision of the manuscript. JS did the statistical analysis, which was reviewed by OB, EV, and FB. JS wrote the first draft and submitted the final version of the manuscript under the supervision of GM. All authors have seen the final submitted manuscript and agree with its contents. JS and GM are the guarantors.

  • Funding: This study was led by the ACTION Study group (Academic Research Organization www.action-coeur.org) with no specific funding

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; the following financial relationships or activities: GC has received a research grant from la Fédération Française de Cardiologie; consultant fees from Abbott Vascular, AstraZeneca, CLS Behring, Daiichi Sankyo, Eli Lilly; lecture fees from Abbott Vascular, AstraZeneca, Biotronik, CLS Behring, Daiichi Sankyo, Eli Lilly, and Iroko Cardio. MC has received grant support and speaker honorariums from Sanofi-Aventis, Bristol-Myers Squibb, and Merck. J-PC has received research grants from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Fondation de France, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consulting fees from Sanofi-Aventis, Eli Lilly, and Bristol-Myers Squibb; and lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, and AstraZeneca. PG has received consulting or board fees and lecture fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, Sanofi-Aventis, and The Medicines Company. KH has received lecture fees from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, Schering-Plough, and The Medicines Company. GM has received support from Abbott Vascular, Boston Scientific, Cordis, Eli Lilly, Fédération Française de Cardiologie, Fondation de France, Guerbet Medical, INSERM, ITC Edison, Medtronic, Pfizer, Sanofi-Aventis, Société Française de Cardiologie, and Stago; consulting or board fees and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cardiovascular Research Foundation, Cleveland Clinic Research Foundation, Daiichi-Sankyo, Duke Institute, Eli Lilly, Europa, Lead-up, GlaxoSmithKline, Institut de Cardiologie de Montreal, Menarini, Nanospheres, Novartis, Pfizer, Portola, Sanofi-Aventis, The Medicines Company, and TIMI study group. CP has received research grants from Sanofi-Aventis and GlaxoSmithKline, and consulting fees from Sanofi-Aventis, and BristolMyersSquibb. JS has received research grants from Sanofi-Aventis, Daiichi-Sankyo, Eli Lilly, Brahms, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consulting fees from Daiichi-Sankyo and Eli Lilly; and speaker honorariums from AstraZeneca, Daiichi Sankyo, Eli Lilly, Iroko Cardio, and Servier. EV has received consulting fees and lecture fees from Abbott, Amgen, Eli Lilly, Pfizer, Sanofi-Aventis, and Servier. UZ has received research grants and speaker honorariums from BMS, Eli Lilly, and Sanofi-Aventis; and consulting and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Portola, and The Medicines Company; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: The dataset, statistical code, and review protocol are available from the corresponding at gilles.montalescot{at}psl.aphp.fr.

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