BoneKEy Reports | BoneKEy Watch

Controversial results from the EVOLVE trial


This large trial involved 3883 dialysis patients with secondary hyperparathyroidism (moderate to severe). All received standard therapy—vitamin D sterols, phosphate binders, or both—but were also randomized to receive either cinacalcet (starting dose of 30 mg daily) or placebo. A 20-week escalation stage followed, with dose increases possible every four weeks, resulting in a daily dose of 60, 90, 120 or 180 mg.

Treatment continued for a median of 21.2 months in the cinacalcet group, while the median exposure to placebo was 17.5 months, with an overall follow-up of 64 months.

The primary composite end point—the time to first cardiovascular event (non-fatal) or time to death—was reached in 48.2% of the cinacalcet group and in 49.2% of the placebo group, suggesting that cinacalcet treatment did not significantly reduce cardiovascular risk.

Editor’s comment: Vascular calcification that induces arterial stiffness and leads to serious cardiovascular events is a major complication of end-stage renal failure/dialysis. These effects and the ensuing mortality have been ascribed to elevated parathyroid hormone (PTH) levels. Yet cinacalcet, a drug that can reduce serum calcium and PTH levels effectively, failed to reduce cardiovascular event risk in this trial, at least in the primary unadjusted intention-to-treat analysis. This is a great disappointment, but the methodological issues, discussed in the accompanying editorial, leave a bitter taste of failed opportunity. Cinacalcet may, in fact, be useful, but this could not be demonstrated.

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