Anticoagulant strategies for ACS: network meta-analysis of 42 randomised trials involving 117,353 patients


Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes. Comprehensive network meta-analysis of 42 randomised trials involving 117,353 patients.

Navarese EP, Andreotti F, Kołodziejczak M, Schulze V, Wolff G, Dias S, Claessen B, Brouwer M, Tarantini G, Iliceto S, Brockmeyer M, Kowalewski M, Lin Y, Eikelboom J, Musumeci G, Lee L, Lip GY, Valgimigli M, Berti S, Kelm M.

Thromb Haemost. 2015 Nov;114(5):933-44. doi: 10.1160/TH14-12-1066. Epub 2015 Jul 16.

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, EMBASE, 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.
Acute coronary syndrome; network meta-analysis; parenteral anticoagulant