A randomized two-by-two comparison of high-dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: the tirofiban evaluation of novel dosing versus abciximab wi

In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 μg/kg) plus 12-hr infusion (0.15 μg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.

Moliterno DJ ，TENACITY Steering Committee and Investigators 《-》

Influence of timing of clopidogrel treatment on the efficacy and safety of bivalirudin in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention: an analysis of the ACUITY (Acute Catheterization and U

Lincoff AM ，Steinhubl SR ，Manoukian SV ，Chew D ，Pollack CV Jr ，Feit F ，Ware JH ，Bertrand ME ，Ohman EM ，Desmet W ，Cox DA ，Mehran R ，Stone GW ，Acute Catheterization and Urgent Intervention Triage strategY of Trial Investigators ... -  《-》

Comparison of heparin, bivalirudin, and different glycoprotein IIb/IIIa inhibitor regimens for anticoagulation during percutaneous coronary intervention: A network meta-analysis.

Numerous GPIs are available for PCI. Although they were tested in randomized controlled trials, a comparison between the different GPI strategies is lacking. Thus, we performed a Bayesian network meta-analysis to compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin and bivalirudin for percutaneous coronary intervention (PCI). MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two independent reviewers for randomized controlled trials comparing high-dose bolus tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare between different anticoagulation strategies for all-cause mortality, myocardial infarction, major adverse cardiovascular events, major bleeding, minor bleeding, need for transfusion, and thrombocytopenia. A total of 41 randomized controlled trials with 38,645 patients were included in the analysis, among which 2654 were randomized to high-dose bolus tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070 to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose bolus tirofiban was associated with a significant reduction in all-cause mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less myocardial infarction and major adverse cardiovascular events but greater bleeding compared with heparin and bivalirudin. There was no difference among the GPI therapies for other outcomes, including myocardial infarction, major adverse cardiovascular events, and major bleeding. Our network meta-analysis of 38,645 patients demonstrated that GPI regimens were associated with a reduction in recurrent myocardial infarction or major adverse cardiovascular events for PCI, while bivalirudin was associated with the lowest risk of bleeding.

Lipinski MJ ，Lee RC ，Gaglia MA Jr ，Torguson R ，Garcia-Garcia HM ，Pichard AD ，Satler LF ，Waksman R ... -  《-》

Efficacy and safety of bivalirudin in patients receiving clopidogrel therapy after diagnostic angiography for percutaneous coronary intervention in acute coronary syndromes.

This study sought to investigate if the efficacy of bivalirudin monotherapy is similar to heparin plus GP IIb/IIIa inhibition in patients with acute coronary syndromes (ACS) treated with clopidogrel following diagnostic angiography. Prior trials have demonstrated that peri-procedural bivalirudin therapy confers similar efficacy as heparin plus GP IIb/IIIa inhibitors, while lowering the risk of bleeding complications in ACS patients undergoing percutaneous coronary interventions (PCI). However, the incidence of adverse ischemic events post-PCI appeared to be higher in patients receiving bivalirudin without adequate pretreatment with clopidogrel. Using the 2004/2005 Cornell Angioplasty Registry, we evaluated 980 consecutive patients undergoing urgent PCI for UA/NSTEMI who were treated with either bivalirudin or UFH plus GP IIb/IIIa inhibitor. We excluded patients who were on chronic clopidogrel therapy or received clopidogrel pretreatment prior to angiography. All patients received a clopidogrel load (≥300-mg dose) immediately before or after the PCI. Long-term all-cause mortality was obtained for 100% of patients, with a mean follow-up of 24.6 ± 7.7 months. Of the 980 study patients, 461 (47.0%) were treated with bivalirudin and 519 (53.0%) patients received UFH plus GP IIb/IIIa inhibitor. DES were used in 88% of PCI; 45% of patients presented with NSTEMI. The incidence of in-hospital death (0.4% vs. 0.2%, P = 0.604), post-procedural MI (6.9% vs. 5.4%, P = 0.351), and MACE including death, stroke, emergent CABG/PCI, and MI (7.6% vs. 5.8%, P = 0.304) were similar in patients treated with bivalirudin versus UFH plus GP IIb/IIIa inhibitors, respectively. The incidence of in-hospital stent thrombosis was similar (0.7% vs. 0%, P = 0.104), while major (0.9% vs. 2.9%, P = 0.034) and minor bleeding (10.4% vs. 18.9%, P < 0.001) was reduced in the bivalirudin-treated group. By two-years of follow-up, after propensity-score adjusted multivariate Cox regression analysis, there was no significant difference in long-term mortality between the two groups (HR 1.18; 95%CI 0.64-2.19, P = 0.598). In patients presenting with ACS and receiving clopidogrel treatment after angiography (before or within 30 min of PCI), peri-procedural bivalirudin monotherapy suppresses acute and long-term adverse events to a similar extent as does UFH plus GP IIb/IIIa inhibitors, while significantly lowering the risk of bleeding complications.

Feldman DN ，Minutello RM ，Bergman G ，Moussa I ，Wong SC ... -  《-》

Efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access: A subgroup analysis from the bivalirudin in acute myocardial infarction versus heparin and GPI plus heparin trial.

To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access. Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain. In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30-day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding. 30-day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30-day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P < 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P > 0.05). The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. © 2016 Wiley Periodicals, Inc.

Wang H ，Li Y ，Cong H ，Ding S ，Liu B ，Li L ，Chen Y ，Jia S ，Jing Q ，Zhao X ，Liu H ，Liang Z ，Li J ，Bao D ，Han Y ... -  《-》