Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors.
OBJECTIVE
To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI).


METHODS
Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors.


METHODS
A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI.


RESULTS
The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding.


RESULTS
We identified 22 randomized trials that enrolled 22,434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone.


CONCLUSIONS
In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.
New York University School of Medicine, New York, NY 10016, USA sripalbangalore@gmail.com.
Sripal
S
Bangalore
New York University School of Medicine, New York, NY 10016, USA.
Bora
B
Toklu
University of Massachusetts, Worcester, MA, USA.
Anupam
A
Kotwal
New York University School of Medicine, New York, NY 10016, USA.
Alexander
A
Volodarskiy
Lincoln Medical Center, Bronx, NY, USA.
Sahil
S
Sharma
Columbia University Medical Center/New York-Presbyterian Hospital, New York, NY, USA.
Ajay J
AJ
Kirtane
New York University School of Medicine, New York, NY 10016, USA.
Frederick
F
Feit
D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D039661:Integrin beta3; D009203:Myocardial Infarction / Q000628:therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011134:Polysaccharides / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
D000925:Anticoagulants; D000991:Antithrombins; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D039661:Integrin beta3; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011134:Polysaccharides; D058921:Purinergic P2Y Receptor Antagonists; D011994:Recombinant Proteins; D006493:Heparin; D000077425:Fondaparinux; C074619:bivalirudin