The EVOLVE Study: Another Disappointment for Nephrologists?

Abstract

The calcimimetic cinacalcet is now being used for years to treat secondary hyperparathyroidism (SHPT) in dialysis patients, allowing a good reduction in PTH levels. In order to evaluate a possible beneficial effect on cardiovascular prognosis, a randomized trial, the EVOLVE (Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events), was conducted in 3,883 dialysis patients affected by moderate to severe SHPT. Patients were randomly assigned to receive cinacalcet or placebo. The primary composite endpoint evaluated was time until death, myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular events. Due to a low statistical power, there was no significant difference between the two arms of the study in the intention-to-treat analysis, despite a higher incidence of hypocalcaemia, nausea, and vomiting in patients treated with cinacalcet. The results of the EVOLVE study have certainly disappointed the nephrological community that would have expected a positive conclusion. Lack of conclusive results and high costs suggest a judicious use of cinecalcet. Nevertheless, even in the absence of conclusive data on hard endpoints it would be unwise to deny the availability of therapeutic strategies that include cinacalcet to patients with severe SHPT and high levels of PTH (PTH >800 pg/mL) refractory to standard therapy and/or hypercalcaemia and/or calciphylaxis and/or high surgical risk to parathyroidectomy.