Cinacalcet’s effects on survival may vary by parathyroid hormone level, with greater impact in patients with severe secondary hyperparathyroidism (SHPT), a new Japanese study suggests.
The Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial did not examine some relevant factors and excluded patients with serum intact parathyroid hormone (iPTH) levels below 300 pg/mL, so researchers conducted a study with patients at different iPTH levels. A team led by Tadao Akizawa, MD, of Showa University School of Medicine, and Noriaki Kurita, MD, of Fukushima Medical University Hospital, examined the effects of cinacalcet initiation in 8,229 chronic kidney disease patients on hemodialysis who had SHPT. About 42% of patients started cinacalcet over the 36 months (2008–2011) of the Mineral and Bone Disorders Outcomes Study for Japanese CKD Stage 5D Patients at a dose of 25–50 mg/day.
The investigators employed marginal structural models (similar to intention to treat analysis) so they could adjust for time-dependent confounders. The models present the average mortality rate that would be expected if no patients and all patients received cinacalcet.
Over an average 33 months, the risk of death from any cause fell by 51% in patients with iPTH levels at or above 500 pg/mL treated with cinacalcet, according to a report in Scientific Reports. The investigators also observed a reduction in cardiovascular hospitalization and mortality for patients with iPTH levels above 300 pg/mL, but the result was not statistically significant. Treated patients with iPTH levels below 300 pg/mL at baseline did not exhibit improved survival, warranting further research.
The EVOLVE trial, which showed no statistically significant benefit of cinacalcet on cardiovascular outcomes, may have been subject to dilution because a good number of treated patients discontinued the drug and a fifth of placebo patients initiated it.
“These findings indicate that decisions about using cinacalcet should take into account the severity of SHPT,” Dr Akizawa and colleagues concluded.