EVOLVEing past Cinacalcet

One of the regular criticisms of nephrology is the lack of good quality randomized controlled trials. This is particularly the case in the world of renal bone disease where we target surrogate endpoints without necessarily knowing for certain what the effect this has on the most important outcome – patient survival. The EVOLVE trial was once such trial which examined the role of cinacalcet in preventing all-cause and cardiovascular mortality. The results of this trial were somewhat ambiguous in that the overall results were negative but this could have been affected by the slightly older age of the treatment group (after adjustment for age, there was a benefit to cinacalcet). There was, however, a wonderful rebuttal to this particular argument in a letter to the editor published later in the NEJM by Giovanni Tripepi.

Overall, the number needed to treat to prevent a single death was 500 and this is balanced by a 62% drop-out rate in the treatment group. There was also a lower rate of parathyroidectomy in the treatment group.

Last month NDT published and ERA-EDTA position statement on the use of calcimimetics in patients on dialysis. Based on a meta-analysis (which was largely derived from the EVOLVE trial), they made the definitive statement that cinacalcet should not be used in patients on dialysis to reduce cardiovascular or all-cause mortality. Further, they pointed out that although the original trials showed that PTH could be successfully lowered using these drugs and that this could reduce the rate of parathyroidectomies, there is no evidence that this has any benefits either beyond the prevention of surgery. They called for a randomized trial of parathyroidectomy vs. cinacalcet for the treatment of intractable hyperparathyroidism with hard endpoints. I second that call.