Calcimimetic agents show short-term benefits for patients with CKD, but side effects vary
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For patients with kidney disease, calcimimetic agents lowered parathyroid hormone levels in the short term, with each agent consisting of a different side-effect profile, according to a systematic study review.
“Secondary hyperparathyroidism is associated with all-cause and cardiovascular mortality, and international clinical practice guidelines suggest that serum [parathyroid hormone] PTH levels should be lowered toward a target range,” Suetonia C. Palmer, MB ChB, PhD, of the University of Otago Christchurch in New Zealand, and colleagues, wrote. “Calcimimetic drugs mimic the action of calcium on calcium-sensing receptors in the parathyroid gland and suppress PTH synthesis and secretion.”
Arguing that evidence is scare regarding the comparative effectiveness and potential side effects (including hypocalcemia, nausea and vomiting) among available calcimimetic medications, the researchers conducted a review of published studies. In total, they examined 36 trials of 11,247 adults with chronic kidney disease-related secondary hyperparathyroidism and focused on trials that compared use of a calcimimetic agent (cinacalcet, etelcalcetide and evocalcet) to another calcimimetic agent or placebo. The researchers noted that all but four trials involved patients on dialysis and that the median follow-up in the studies was 26 weeks.
Results showed calcimimetic agents were more likely to achieve target PTH levels with “high or moderate certainty” vs. placebo.
Considering specific agents, the researchers found that compared with placebo etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR = 4.93) and cinacalcet (OR = 2.78), though it caused more hypocalcemia than the other agents.
Cinacalcet was found to cause more nausea than placebo, while also increasing the odds for nausea compared to evocalcet. Similarly, etelcalcetide induced more nausea than placebo or evocalcet, but this was to a “lesser extent” than cinacalcet, according to the researchers.
“Etelcalcetide was the most efficacious calcimimetic agent for lowering serum PTH levels, but incurred hypocalcemia, nausea and vomiting,” they elaborated. “Cinacalcet ranked worst for nausea and had somewhat lower effectiveness. Evocalcet had lower effectiveness for achieving target PTH levels while incurring fewer adverse effects.”
The researchers further noted that differences in long-term effects between the agents regarding risk for mortality, cardiovascular endpoints (cardiovascular mortality or heart failure) or fractures remains undetermined.
“At present,” they concluded, “the benefits of calcimimetic agents are limited to lowering serum PTH levels during short-term follow-up.”
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