Sharon M Moe1, Glenn M Chertow2, Patrick S Parfrey2, Yumi Kubo2, Geoffrey A Block2, Ricardo Correa-Rotter2, Tilman B Drüeke2, Charles A Herzog2, Gerard M London2, Kenneth W Mahaffey2, David C Wheeler2, Maria Stolina2, Bastian Dehmel2, William G Goodman2, Jürgen Floege2. 1. From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.). smoe@iupui.edu. 2. From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
Abstract
BACKGROUND:Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events. METHODS AND RESULTS: This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99). CONCLUSIONS: Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.
RCT Entities:
BACKGROUND:Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events. METHODS AND RESULTS: This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99). CONCLUSIONS: Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.
Authors: Sharon M Moe; Leah Wetherill; Brian Scott Decker; Dongbing Lai; Safa Abdalla; Jin Long; Matteo Vatta; Tatiana M Foroud; Glenn M Chertow Journal: Clin J Am Soc Nephrol Date: 2017-06-19 Impact factor: 8.237
Authors: L-C Desbiens; A Sidibé; R-V Ung; C Fortier; M Munger; Y-P Wang; S-K Bisson; K Marquis; M Agharazii; F Mac-Way Journal: Osteoporos Int Date: 2018-06-29 Impact factor: 4.507
Authors: Joerg C Schefold; Gerasimos Filippatos; Gerd Hasenfuss; Stefan D Anker; Stephan von Haehling Journal: Nat Rev Nephrol Date: 2016-08-30 Impact factor: 28.314
Authors: Patrick S Parfrey; Geoffrey A Block; Ricardo Correa-Rotter; Tilman B Drüeke; Jürgen Floege; Charles A Herzog; Gerard M London; Kenneth W Mahaffey; Sharon M Moe; David C Wheeler; Glenn M Chertow Journal: Clin J Am Soc Nephrol Date: 2015-11-27 Impact factor: 8.237