title: Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes. Comprehensive network meta-analysis of 42 randomised trials involving 117,353 patients.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany, E-mail: elianonavarese@gmail.com.
authors.forename: Eliano Pio
authors.initials: EP
authors.lastname: Navarese
authors.forename: Felicita
authors.initials: F
authors.lastname: Andreotti
authors.forename: Michalina
authors.initials: M
authors.lastname: Kołodziejczak
authors.forename: Volker
authors.initials: V
authors.lastname: Schulze
authors.forename: Georg
authors.initials: G
authors.lastname: Wolff
authors.forename: Sofia
authors.initials: S
authors.lastname: Dias
authors.forename: Bimmer
authors.initials: B
authors.lastname: Claessen
authors.forename: Marc
authors.initials: M
authors.lastname: Brouwer
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tarantini
authors.forename: Sabino
authors.initials: S
authors.lastname: Iliceto
authors.forename: Maximilian
authors.initials: M
authors.lastname: Brockmeyer
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kowalewski
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Lin
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.forename: Leong
authors.initials: L
authors.lastname: Lee
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.forename: Sergio
authors.initials: S
authors.lastname: Berti
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy*; D000925:Anticoagulants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants
keywords: Acute coronary syndrome; network meta-analysis; parenteral anticoagulant