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Moe et al. two new studies Analysis of secondary endpoints from the failed EVOLVE trial
DOI:10.1038/bonekey.2015.131
In two new papers, Moe et al. report secondary analyses from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial. In this trial, 3883 hemodialysis patients undergoing with secondary hyperparathyroidism, were treated with the calcimimetic cinacalcet or placebo for five years or more. The main analysis could not demonstrate any significant difference between treated and placebo group for the primary end points time to death or first cardiovascular event (non-fatal).
The first paper focuses on the impact of cinacalcet on serum levels of fibroblast growth factor-23 (FGF23), which is often elevated in kidney disease patients.
Serum samples obtained from 2602 patients at baseline and at week 20 were analyzed for FGF23 levels. 68% of patients in the cinacalcet group showed a reduction in FGF23 of 30% or more, compared to 28% in the placebo group. Patients in the cinacalcet group who showed the greatest drop in FGF23 were found to have lower rates of sudden cardiac death (relative hazard, 0.57; 95% CI, 0.37–0.86), heart failure (relative hazard, 0.69; 95% CI, 0.48–0.99) and cardiovascular mortality (relative hazard, 0.66; 95% CI, 0.50–0.87).
The second study uses data generated from a planned secondary analysis of the EVOLVE trial, which investigated time to first clinical fracture event. The proportion of patients suffering clinical fractures was slightly lower in the placebo group than the treated group (12.2% cf. 13.2% in the cinacalcet group). In an effort to account for differences in baseline, the presence of more than one fracture and time of exposure to treatment, the authors then conducted various statistical analyses. After adjustment, relative hazard for fracture fell from 0.89 (95% confidence interval [95% CI], 0.75 to 1.07) to 0.71 (95% CI, 0.58 to 0.87).
The authors conclude that cinacalcet did have some benefits, particularly in older patients who were more at risk of fractures than younger subjects. They suggest treatment with cinacalcet might reduce clinical fracture rates by between 16% and 29%.
Editor’s comment: The avatars of the failed EVOLVE Study continue…Here, two studies suggest that a subgroup of older subjects could experience clinical benefits with respect to fractures, and those with better a pharmacological response might obtain a reduction in cardiovascular risk. However these secondary analyses remain at best hypothesis-generating.
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