Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental 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. METHODS: In 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. RESULTS: A 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 [CI], 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. CONCLUSIONS: In 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. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.

The European Society of Cardiology Cardiac Resynchronization Therapy Survey II: A comparison of cardiac resynchronization therapy implantation practice in Europe and France.

BACKGROUND: The first European Cardiac Resynchronization Therapy (CRT) Survey, conducted in 2008-2009, showed considerable variations in guideline adherence and implantation practice. A second prospective survey (CRT Survey II) was then performed to describe contemporary clinical practice regarding CRT among 42 European countries. AIM: To compare the characteristics of French CRT recipients with the overall European population of CRT Survey II. METHODS: Demographic and procedural data from French centres recruiting all consecutive patients undergoing either de novo CRT implantation or an upgrade to a CRT system were collected and compared with data from the European population. RESULTS: A total of 11,088 patients were enrolled in CRT Survey II, 754 of whom were recruited in France. French patients were older (44.7% aged≥75 years vs 31.1% in the European group), had less severe heart failure symptoms, a higher baseline left ventricular ejection fraction and fewer co-morbidities. Additionally, French patients had a shorter intrinsic QRS duration (19.1% had a QRS<130ms vs 12.3% in the European cohort). Successful implantation rates were similar, but procedural and fluoroscopy times were shorter in France. French patients were more likely to receive a CRT pacemaker than European patients overall. Of note, antibiotic prophylaxis was reported to be administered less frequently in France, and a higher rate of early device-related infection was observed. Importantly, French patients were less likely to receive optimal drugs for treating heart failure at hospital discharge. CONCLUSION: This study highlights contemporary clinical practice in France, and describes substantial differences in patient selection, implantation procedure and outcomes compared with the other European countries participating in CRT Survey II.

Therapeutic patient education and all-cause mortality in patients with chronic heart failure: a propensity analysis.

BACKGROUND: Meta-analyses of disease management programs have shown favorable effects in chronic heart failure. Therapeutic patient education forms an integral part of these programs and may influence mortality per se. We aimed to determine the relationship between therapeutic patient education applied in routine clinical practice and long-term mortality in chronic heart failure. METHODS: From 2007 to 2010 (median follow-up: 27.2 months), heart failure patients were prospectively enrolled in a multicenter, 'real-world', French cohort by centers previously trained in therapeutic patient education. As educated and non-educated patient profiles were expected to differ, mortality was assessed using conventional multivariate analyses and analyses made on propensity-matched cohorts for the application of therapeutic patient education. RESULTS: Of the 3237 patients who participated in the study (67.5 years; 69.5% men), 2347 were educated (72.5%) and 890 were not educated (27.5%). Non-educated patients were older, more often female, and more severely diseased than educated patients. All-cause mortality was 17.3% in the educated group vs. 31.0% in the non-educated group (adjusted HR 0.70, 95% CI 0.58-0.84, P<.001). This association remained in paired groups after adjustment for all baseline covariates excluding (model 1) or including (model 2) cardiovascular medications and propensity score (HR 0.72, 95% CI 0.58-0.90, P=.003; HR 0.73, 95% CI 0.59-0.90, P=.004, respectively). CONCLUSION: In chronic heart failure, therapeutic patient education by trained healthcare professionals appears associated with lower all-cause mortality. These data may have important implications in terms of healthcare organization, because they suggest that therapeutic patient education should be developed in all types of cardiology centers.