Cinacalcet plus low-dose vitamin D therapy may attenuate progression of coronary artery calcification (CAC) compared with flexible vitamin D therapy alone in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), according to a new study.

It is well documented that CAC is common and progressive in HD patients. Researchers theorize that CAC may be aggravated by elevated plasma parathyroid hormone (PTH) and/or calcium (Ca) and phosphorus (P) levels.

In the new study, researchers randomized 360 HD patients with SHPT and detectable CAC to treatment with cinacalcet (30-180 mg a day) plus low-dose vitamin D or to flexible vitamin D therapy. In both arms of the study, Ca-based phosphate binders were used exclusively and the therapeutic target for PTH was 150-300 pg/mL. The primary end point of the study was the percent change in Agatston CAC score from baseline to week 52. Additional analyses were also conducted using the volume score, and the investigators analyzed the change in Agatston calcium score for the aorta.

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The study further showed that Agatston CAC scores increased by 31% from baseline in the flexible vitamin D group and by 24% in the cinacalcet group. The volume CAC scores increased by 30% from baseline in the flexible vitamin D group but only by 22% in the cinacalcet group, and the Agatston aorta scores increased by 33% in the flexible vitamin D group but only 20% in the cinacalcet group.

In addition, the median plasma PTH levels decreased by 65 pg/mL from baseline at week 52 in the flexible vitamin D group and by 132 pg/mL in the cinacalcet group.  The mean serum Ca increased by 0.17 mg/dL in the flexible vitamin D group but decreased by 0.51 mg/dL in the cinacalcet group and the serum P decreased by 0.24 mg/dL in the flexible vitamin D group and by 0.92 mg/dL in the cinacalcet group.

Although the primary end point for the percentage of change in CAC scores was not statistically significant, the difference between groups for the change in volume score was, said study investigator William Goodman, MD, Clinical Research Medical Director for Global Development at Amgen Inc, Thousand Oaks, Calif.

Biochemical control of SHPT was better with cinacalcet plus low dose vitamin D, which may help account for the trend toward less progression of cardiovascular calcification in the cinacalcet group, Dr. Goodman observed. Study results support the hypothesis that a treatment strategy including cinacalcet may favorably affect the progression of cardiovascular calcification compared with traditional vitamin D therapy, he said.

“Most importantly, we think that choices about treatment strategies for secondary hyperparathyroidism may slow the progression of established vascular calcification in this population,” Dr. Goodman told Renal & Urology News. “Vascular calcification is thought to be a significant contributor to the very high cardiovascular mortality rate. We readily acknowledge that it is not a validated surrogate. It doesn’t predict events. So, these data are encouraging, but they are preliminary.”

A large prospective trial is underway to examine mortality and cardiovascular events in HD patients treated with cinacalcet. Data from that study are expected to be available sometime next year, Dr. Goodman said.