BACKGROUNDExperimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODSIn a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTSA total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval, 0.78 to 1.39; P = 0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONSIn patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. ( n engl j med 373;11 nejm.org September 10, 2015 1022T h e ne w e ngl a nd jou r na l o f m e dicine O ver the past three decades, major progress has been made in the treatment of patients with ST-segment elevation myocardial infarction (STEMI).1 Nevertheless, the rates of death, heart failure, and recurrent ischemic events occurring in the first year after infarction remain unacceptably elevated in this highrisk population. Although many advances have been made in the development of methods to reopen the culprit coronary artery and prevent reocclusion, there is currently no specific treatment that targets myocardial reperfusion injury, which is a paradoxical form of myocardial damage that occurs as a result of the restoration of vessel patency.2 Growing evidence from experimental studies and small-size proof-of-concept clinical trials shows that reperfusion injury contributes greatly to the final infarct size.3-5 Preclinical studies indicate that the opening of the mitochondrial permeability transition pore (PTP) in the inner mitochondrial membrane plays a major role in reperfusion injury. ...

Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding.

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In this study, pentasaccharide given together with alteplase was safe and as effective as unfractionated heparin in restoring coronary artery patency. Prolonged administration of pentasaccharide was associated with a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patients presenting with ST-segment elevation acute myocardial infarction.