Cinacalcet, FGF23, and Cardiovascular Disease in Hemodialysis | Journal Scan

Jun 18, 2015
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Authors:
Moe SM, Chertow GM, Parfrey PS, et al., on behalf of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial Investigators.
Citation:
Cinacalcet, FGF23 and Cardiovascular Disease in Hemodialysis: The EVOLVE Trial. Circulation 2015;Jun 9:[Epub ahead of print].
Summary By:
Debabrata Mukherjee, MD, FACC

Study Questions:

What are the effects of the calcimimetic cinacalcet (vs. placebo) on reducing serum FGF23, and are changes in FGF23 associated with death and cardiovascular events?

Methods:

This was a secondary post hoc 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 endpoint was time to death or the first nonfatal cardiovascular event (myocardial infarction hospitalization for angina, heart failure, or a peripheral vascular event).

Results:

This analysis included 2,985 patients (77% of randomized) with serum samples at baseline and 2,602 (67%) patients with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% vs. 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 [CI], 0.69-0.98), cardiovascular mortality (HR, 0.66; 95% CI, 0.50-0.87), sudden cardiac death (HR, 0.57; 95% CI, 0.37-0.86), and heart failure (HR, 0.69; 95% CI, 0.48-0.99).

Conclusions:

The authors concluded that treatment with cinacalcet significantly lowers serum FGF23.

Perspective:

This post hoc analysis of the EVOLVE trial reports that cinacalcet reduced serum FGF23, and this decrease was associated with lower risks of cardiovascular mortality and selected cardiovascular events, including heart failure and sudden death. Given significant study limitations including significant missing data, study drug discontinuations, and possible ‘healthy responder’ effect, these findings need to be validated in a prospective randomized trial with appropriate and complete follow-up.

Keywords: Angina Pectoris, Death, Sudden, Cardiac, Heart Failure, Hospitalization, Hyperparathyroidism, Secondary, Kidney Failure, Chronic, Metabolic Syndrome, Mortality, Myocardial Infarction, Naphthalenes, Peripheral Vascular Diseases, Phosphates, Renal Dialysis, Secondary Prevention


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