Cinacalcet, FGF23 and Cardiovascular Disease in Hemodialysis: The EVOLVE Trial
Background—Patients with kidney disease have disordered bone and mineral metabolism including elevated serum concentrations of fibroblast growth factor 23 (FGF23). The latter 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 (iPTH ≥ 300 pg/mL). The primary study end point was time to death or the 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 (67%) patients with samples at both baseline and week 20. The results demonstrated 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 endpoint (relative hazard (HR) 0.82; 95% confidence interval (95% CI) 0.69, 0.98), cardiovascular mortality (HR 0.66; 0.50, 0.87), sudden cardiac death (HR 0.57; 0.37, 0.86), and heart failure (HR 0.69; 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 Information—ClinicalTrials.gov. Identifier: NCT00345839.
- Received October 21, 2014.
- Revision received March 16, 2015.
- Accepted April 22, 2015.