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The optimal anticoagulant for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) remains controversial. And the efficacy and safety of bivalirudin compared with unfractionated heparin (UFH) in patients with ACS undergoing urgent PCI versus elective PCI has not been reported. Therefore, we performed a meta-analysis that compared the two anticoagulation regimens in these two different PCI groups to assess different clinical benefits.
Literature was searched in PubMed, EMBASE, Cochrane Library and Clinical Trials from database inception. Suitable randomized trials were picked up and then a meta-analysis comparing bivalirudin with UFH, with separate analyses in urgent PCI group versus elective PCI group, was performed. The primary efficacy endpoint was 30-day incidence of major adverse cardiovascular events (MACE), the secondary efficacy endpoints were 30-day incidence of all-cause mortality, cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR), acute stent thrombosis (ST), sub-acute stent thrombosis and any stent thrombosis, all up to 30-day post hospitalization. The safety endpoint was major bleeding. Net adverse clinical events (NACE) were calculated as the composite of MACE and major bleeding. Subgroup analyses were also conducted according to UFH plus routine glycoprotein IIb/IIIa inhibitors(GPI) use or plus bailout GPI use.
Finally, 13 randomized controlled trials involving 23500 patients were included. The risk ratios (RRs) were calculated using random-effects models. In 6 trials of patients undergoing urgent PCI (16188 patients), compared with UFH, bivalirudin significantly decreased the risk of all-cause mortality (RR 0.80; 95%CI 0.67 to 0.96; p=0.02; I2=0%), cardiac mortality (RR 0.76; 95%CI 0.59 to 0.98; p=0.04; I2=0%) and major bleeding (RR 0.61; 95% 0.44 to 0.83; p=0.002, I2=70%), but increased the risk of MI (RR 1.32; 95%CI 1.02 to 1.72; p=0.04; I2=20%), acute ST (RR 2.76; 95% CI 1.66 to 4.58; p<0.0001; I2=11%) and any-ST (RR 1.59; 95% CI 1.07 to 2.36; p=0.02; I2=34%). In 7 trials of patients undergoing elective PCI (7312 patients), compared with UFH, bivalirudin was associated with a lower risk of major bleeding (RR 0.68; 95% CI 0.51 to 0.91; p=0.01; I2=3%), but no significant difference was observed in the incidence of MACE, MI, all-cause mortality, TVR, any-ST and NACE. Unfortunately, no cardiac mortality, acute and sub-acute ST data were reported in trials of elective PCI group. From the heparin subgroup analyses, we observed that in urgent PCI group the risk of major bleeding significantly decreased but varied depending on routine GPI use with UFH (RR 0.49; 95% CI 0.35 to 0.70, p<0.0001, I2=41%) or bailout GPI use (RR 0.73; 95% CI 0.39 to 1.34; p=0.31; I2=80%), while in elective PCI group the risk of major bleeding significantly decreased as well but not varied whether routine GPI use or bailout GPI use (RR 0.69; 95% CI 0.50 to 0.97; p=0.03; I2=7%).
Bivalirudin may confer an advantage over UFH in patients undergoing urgent PCI attributed to the reduced risk of major bleeding, all-cause mortality and cardiac mortality. However, the benefit of bivalirudin may be reduced or disappeared in patients undergoing elective PCI.