Hypocalcemia and cardiovascular mortality in cinacalcet users

Area of Science:

• Nephrology
• Cardiology
• Clinical Pharmacology

Background:

• Calcimimetics are frequently prescribed to hemodialysis patients to manage secondary hyperparathyroidism and influence serum calcium levels.
• While current guidelines suggest low calcium levels induced by calcimimetics may be benign, evidence from large observational studies is limited.
• This study investigates the association between serum calcium levels and cardiovascular mortality in calcimimetic users within a Japanese dialysis registry.

Purpose of the Study:

• To examine the relationship between serum calcium levels and cardiovascular mortality in patients undergoing maintenance hemodialysis or hemodiafiltration.
• To specifically assess this association in patients using calcimimetics, including cinacalcet.
• To determine if hypocalcemia, particularly transiently induced, poses a risk for cardiovascular death.

Main Methods:

• A 9-year prospective cohort study utilizing a nationwide Japanese registry for dialysis patients, with baseline data from end-2009.
• Inclusion criteria encompassed patients on maintenance hemodialysis or hemodiafiltration.
• Cox proportional hazard regression analyses were performed using baseline, time-dependent, and time-averaged models.

Main Results:

• Cinacalcet was used by 12.7% of the 180,136 patients in the cohort.
• In the time-dependent model, the lowest calcium decile (<8.4 mg/dL) was significantly associated with higher cardiovascular mortality in both cinacalcet users (HR 1.32) and the overall cohort (HR 1.15).
• Hypocalcemia was linked to increased risk of sudden death, hemorrhagic stroke, heart failure, and ischemic heart disease, irrespective of cinacalcet use.

Conclusions:

• Transient hypocalcemia is associated with an elevated risk of cardiovascular death, independent of cinacalcet therapy.
• Healthcare providers should be vigilant regarding hypocalcemia, even when transiently induced by calcimimetics like cinacalcet.
• Further attention to managing serum calcium levels in dialysis patients using calcimimetics is warranted to mitigate cardiovascular risks.