Randomized Comparison of Eptifibatide Versus Abciximab in Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction Results of the EVA-AMI Trial

ObjectivesThe aim of this study was to compare eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI).BackgroundThe glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, eptifibatide, and abciximab in primary PCI.MethodsA total of 427 patients with ST-segment elevation myocardial infarctions <12 h and planned primary PCI were randomized to double-bolus eptifibatide (n = 226) followed by a 24-h infusion or single-bolus abciximab (n = 201) followed by a 12-h infusion. In this noninferiority trial, the primary end point was the incidence of complete (≥70%) ST-segment resolution (STR) 60 min after PCI, a measure of myocardial reperfusion. The assumption was a 60% complete STR rate in the abciximab group. The noninferiority margin was set to 15%.ResultsThe incidence of complete STR at 60 min after PCI in the intention-to-treat analysis was 62.6% after eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50); reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4% versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction, and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5% versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were observed after eptifibatide and abciximab, respectively.ConclusionsEptifibatide as an adjunct to primary PCI is equally as effective as abciximab with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial Infarction [STEMI]; NCT00426751

AT 1} receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NOS inhibition in humans

International audienceWhether AT1 receptor blockade can prevent the decrease in conduit artery flow-mediated dilatation during NO-synthase inhibition by endothelial alternative pathways has not previously been explored in humans. In 12 healthy subjects, we measured radial artery diameter (echotracking) and flow (Doppler) during flow-mediated dilatation induced by sustained reactive hyperemia in control period and following NO-synthase inhibition (L-NMMA: 1.5 mg.min -1}.L -1}), after single oral administration of telmisartan (80 mg) or placebo, during a double-blind, randomized, cross-over study. In 6 volunteers, we also assessed the roles of prostacyclin and endothelium-derived hyperpolarizing factor during radial flow-mediated dilatation after AT 1} receptor blockade by oral administration of aspirin (500 mg) alone and associated with L-NMMA and by the addition of the cytochrome epoxygenases inhibitor fluconazole (0.37 mg.min -1}.L -1}). Telmisartan did not affect radial artery flow-mediated dilatation in control period (placebo: 10.9±0.6% vs. telmisartan: 9.9±0.7%) but prevented its decrease after L-NMMA (placebo: 9.3±0.8% vs. telmisartan: 12.6±1.2%, P<0.05) with no modification in baseline parameters, hyperemia and radial artery endothelium-independent dilatation to sodium nitroprusside. Moreover, in telmisartan-treated subjects, the radial flow-mediated dilatation, compared with control (9.0±1.0%), was not modified by aspirin alone (9.4±0.7%) or associated with L-NMMA (9.5±0.5%) but in fact was reduced by the combination of aspirin, L-NMMA and fluconazole (7.5±0.6%, P<0.05). These results demonstrate that AT 1} receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NO-synthase inhibition in humans suggesting the development of an endothelial compensatory mechanism. This mechanism seems to be independent of prostacyclin and could possibly be related to an endothelium-derived hyperpolarizing factor release