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.