Weltgrößte Studie der Dialysepatienten, in der der Einfluss von Parathormonen auf Herz-Kreislaufereignisse untersucht wurde

 

Glenn M. Chertow; Geoffrey A. Block; Ricardo Correa-Rotter; Tilman B. Drüeke; Jürgen Floege; William G. Goodman; Charles A. Herzog; Yumi Kubo; Gerard M. London; Kenneth W. Mahaffey; T. Christian H. Mix; Sharon M. Moe; Marie-Louise Trotman; David C. Wheeler; Patrick S. Parfrey

Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis, N Engl J Med, Nov 3. 2012

http://www.ncbi.nlm.nih.gov/pubmed/23121374

Zusammenfassung

In dieser weltgrößten und längsten Studie in Dialysepatienten wurde der Effekt einer neuen Therapie (sog. Kalzimimetika) auf das Überleben bzw. kardiovaskuläre Ereignisse in Patienten an der Dialyse getestet. Obwohl der primäre Endpunkt sich nicht signifikant in den beiden Studienarmen nicht signifikant unterschieden, zeigen Sekundäranalysen hochsignifikante Effekte zugunsten des Kalzimimetikums. Prof. Floege war als Mitglied der Studienleitung an der Konzeption, Durchführung, Auswertung und Publikation der Studie beteiligt.

Abstract

Background Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. Methods In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. Results The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. Conclusions In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839 .).