Comparative Effectiveness of Alternative Treatment Approaches to Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: An Observational Trial Emulation

Rationale & Objective: Optimal approaches treat secondary hyperparathyroidism (SHPT) patients on maintenance hemodialysis (HD) have yet to be established in randomized controlled trials (RCTs). Study Design: Two observational clinical trial emulations. Setting & Participants: Both emulations included adults receiving in-center HD from a national dialysis organization. The patients who had SHPT in the period between 2009 and 2014, were insured for >_180 days by Medicare as primary payer, and did not have contraindications or poor health status limiting theoretical trial participation.Exposure: The parathyroid hormone (PTH) Target Trial emulation included patients with new-onset SHPT (first PTH 300-600 pg/mL), with 2 arms defined as up-titration of either vitamin D sterols or cinacalcet within 30 days (lower target) or up-titration (higher target). The Agent Trial emulation included patients with a PTH >_300 pg/mL while on >_6 mu g weekly of vitamin D sterol (paricalcitol equivalent dose) and no prior history of cinacalcet. The 2 arms were defined by the first dose or agent change within 30 days (vitamin D-favoring [vitamin-D was up-titrated] cinacalcet-favoring [cinacalcet was added] nondefined [neither applies]). Multiple trials patient were allowed in trial 2.Outcome: The primary outcome was all-cause death over 24 months; secondary outcomes included cardiovascular (CV) hospitalization or the composite of CV hospitalization or death. Analytical Approach: Pooled logistic regression. Results: There were 1,152 patients in the PTH Target Trial (635 lower target and 517 higher target). There were 2,726 unique patients with 6,727 patient trials in the Agent Trial (6,268 vitamin D-favoring trials and 459 cinacalcetfavoring trials). The lower PTH target approach was associated with reduced adjusted hazard of death (HR, 0.71 [95% CI, 0.52-0.93]), CV hospitalization (HR, 0.78 [95% CI, 0.63-0.9 8]), and their composite (HR, 0.74 [95% CI, 0.61-0.8 9]). The cinacalcet-favoring approach demonstrated lower adjusted hazard of death compared to the vitamin D-favoring approach (HR, 0.79 [95% CI, 0.62-0.9 9]), but not of CV hospitalization or the composite outcome. Limitations: Potential for residual confounding; low use of cinacalcet with low power. Conclusions: SHPT management that is focused on lower PTH targets may lower mortality and CV disease in patients receiving HD. These findings should be confirmed in a pragmatic randomized trial.