Cinacalcet HCl and concurrent low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: the ACHIEVE study results

Abstract

Background and objectives: Patients with chronic kidney disease (CKD) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) was established to guide treatment practices for these disorders. The ACHIEVE study was designed to test two treatment strategies for achieving KDOQI goals.

Design, setting, participants, measurements: Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study. Subjects were randomly assigned to treatment with either cinacalcet and low-dose vitamin D (Cinacalcet-D) or flexible vitamin D alone (Flex-D) to achieve KDOQI-recommended bone mineral targets. ACHIEVE included a 6-week screening phase, including vitamin D washout, a 16-week dose-titration phase, and an 11-week assessment phase.

Results: Of 173 subjects enrolled, 83% of Cinacalcet-D and 67% of Flex-D subjects completed the study. A greater proportion of Cinacalcet-D versus Flex-D subjects had a >30% reduction in parathyroid hormone (PTH) (68% versus 36%, P < 0.001) as well as PTH <300 pg/ml (44% versus 23%, P = 0.006). The proportion of subjects simultaneously achieving targets for intact PTH (150-300 pg/ml) and calcium-phosphorus product (Ca x P) (<55 mg2/dl2) was also greater (21% versus 14%), but this was not statistically significant. This was attributable to 19% of Cinacalcet-D subjects with a PTH value below the KDOQI target range.

Conclusions: Achievement of KDOQI targets was difficult, especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm.

Figures

Figure 1.

Intact parathyroid hormone (iPTH) (A), calcium-phosphorus product (Ca × P) (B), calcium (Ca) (C), and phosphorus (P) (D) values recorded at each scheduled visit for subjects receiving either cinacalcet plus constant low-dose vitamin D (Cinacalcet-D) or flexible vitamin D (Flex-D). Data presented as median ± interquartile range. SCR, screening phase (previtamin D washout); BL, baseline (postvitamin D washout).

Figure 2.

Median percent changes from baseline to assessment values for intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca × P). Cinacalcet-D, n = 75; Flex-D, n = 64; *P < 0.001; †P = 0.003.

Figure 3.

Proportion of subjects reaching additional intact parathyroid hormone (iPTH) targets by treatment group. Cinacalcet-D, n = 75; Flex-D, n = 64; *P = 0.006, †P = 0.009, ‡P < 0.001; Ca × P, calcium-phosphorus product.

Figure 4.

Weekly vitamin D dose (A) and daily cinacalcet dose (B) at each measured time point. Data presented as mean ± standard error for subjects that received vitamin D. Zero doses are included. Vitamin D doses are presented as paricalcitol equivalents, where 2 μg paricalcitol equals 1 μg doxercalciferol. SCR, screening phase (previtamin D washout); BL, baseline (postvitamin D washout). Arrow indicates day 1 of treatment.