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Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial
Patrick H Pun1, Safa Abdalla2, Geoffrey A Block3
1Department of Medicine, Duke University, Durham, North Carolina, USA.
Insights
Cinacalcet effectively lowers serum calcium in hemodialysis patients. This study found no link between dialysate calcium levels or serum-dialysate gradients and cardiovascular event risks when using cinacalcet.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- Abnormal calcium regulation in hemodialysis patients is associated with increased cardiovascular event risk.
- Cinacalcet, a calcimimetic, reduces serum calcium by suppressing parathyroid hormone secretion.
- Observational studies suggest risks linked to dialysate calcium concentration and serum-dialysate gradients.
Purpose of the Study:
- To investigate the risks associated with dialysate calcium and serum-dialysate gradients in the context of cinacalcet use.
- To determine if baseline dialysate calcium or serum-dialysate gradients modify cinacalcet's effect on cardiovascular outcomes in hemodialysis patients.
Main Methods:
- Analysis of data from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial.
- Inclusion of 3883 hemodialysis patients randomized to cinacalcet or placebo.
- Examination of baseline dialysate calcium concentration and serum-dialysate calcium gradients as modifiers of cinacalcet's effect on adjudicated cardiovascular endpoints.
Main Results:
- No association was found between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the examined cardiovascular endpoints.
- Neither dialysate calcium concentration nor serum-dialysate calcium gradient significantly modified the effect of cinacalcet on cardiovascular death or major cardiovascular events.
- Serum calcium concentrations significantly decreased in the cinacalcet group, with infrequent changes in dialysate calcium in both groups.
Conclusions:
- The effects of cinacalcet on cardiovascular death and major cardiovascular events in hemodialysis patients are not altered by dialysate calcium prescription or serum-dialysate calcium gradients.
- Dialysate calcium management strategies do not appear to influence the cardiovascular benefits of cinacalcet in this patient population.
Abstract:
Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.
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