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Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30 days. The primary safety end point was the incidence of 30-day non–coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30 days and 1 year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; p interaction = 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; p interaction = 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non–access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p = 0.03), which was consistent between patients with or without DM (p interaction = 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status.

In the EVOLUTION OFF trial, we evaluated the safety and efficacy of bivalirudin during off-pump coronary artery bypass grafting as compared with heparin-protamine. In this subanalysis of EVOLUTION OFF data of bivalirudin-treated patients, we assessed the pharmacokinetics (PK) and effectiveness of bivalirudin anticoagulation to achieve target activated clotting time (ACT)+ values. Data from 101 patients were assessed. A bolus of 0.75 mg/kg of bivalirudin was followed by a continuous infusion of 1.75 mg x kg(-1) x h(-1) during the grafting procedure. An ACT+ value of >300 s was the target. In four patients, PK data for bivalirudin were obtained. Only in exceptional cases were repeat fractional boluses or an increase of the infusion rate required. Assessment of the PK data showed a mean concentration of bivalirudin after the initial bolus of 11.0 +/- 0.53 microg/mL and a mean concentration during infusion of 11.2 +/- 2.32 microg/mL. Pearson's correlation between bivalirudin concentrations and ACT+ values was 0.92. Bivalirudin PK data consistently exceeded concentrations of 6.5 microg/mL, which have been evaluated as effective during percutaneous coronary intervention. The correlation between bivalirudin levels and ACT+ values was good, and the target ACT+ values were almost always achieved. These results suggest that bivalirudin, given according to the current protocol, provides reliable and effective anticoagulation during off-pump coronary artery bypass graft surgery.

Udgivelsesdato: 2009-May AIMS: The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes, overall and by treatment strategy, in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: In the ACUITY trial, 13,819 patients with moderate and high-risk ACS were randomised to either heparin (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin alone. Per operator choice, femoral access was utilised in 11,989 patients (93.8%) and radial access in 798 patients (6.2%). There was no significant difference in composite ischaemia between the radial and femoral approaches at 30 days (8.1% vs 7.5%, p=0.18) or 1 year (14.7% vs 15.5%, p=0.77), although fewer major bleeding complications occurred with the use of radial access (3.0%vs4.8%, p=0.03). Use of bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access (3.0% vs 5.8%, p