NEW YORK (Reuters Health) – In the PRIMO trial, treatment with vitamin D2 (paricalcitol) did not improve measures of cardiac structure, function or left ventricular mass in patients with chronic kidney disease, as researchers had hoped.
The authors of a commentary published with the study February 15 in the Journal of the American Medical Association say, “At this time, paricalcitol cannot be recommended for patients with CKD.”
CKD has adverse effects on vitamin D metabolism. Vitamin D deficiency is common in this patient population, reaching up to 80% of patients with stage three to five disease. “There is much interest in vitamin D and several studies suggest there may be a link between vitamin D and heart disease,” Dr. Ravi Thadhani of Massachusetts General Hospital, Boston, explained in an email to Reuters Health.
“We specifically examined the effect of a potent form of vitamin D and cardiac structure and function and found no major effect over a one year period. We did find other interesting effects such as a reduction in episodes of cardiac related hospitalizations from heart failure, but these require additional studies to confirm,” Dr. Thadhani added.
The PRIMO trial was conducted in 11 countries during 2008-2010. It enrolled 227 patients (mostly hypertensive men) with CKD (estimated GFR 15-60 mL/min/1.73m²) and mild to moderate left ventricular hypertrophy. Study subjects were randomly allocated to receive by mouth 2 micrograms per day of paricalcitol (n=115) or matching placebo (n=112) for 48 weeks.
The researchers say reductions in parathyroid hormone levels were noted at four weeks in the paricalcitol group and these levels were maintained in the normal range throughout the study.
However, neither left ventricular mass index at 48 weeks (the primary outcome) nor any other of the 10 assessed parameters of cardiac structure or function (including measures of diastolic function) improved in patients taking paricalcitol compared to those taking placebo.
Paricalcitol appeared to be associated with fewer cardiovascular-related hospitalizations (1 vs 8 with placebo), as well as an attenuated increase in blood levels of B-natriuretic peptide (BNP), but a greater incidence of hypercalcemia (22.6% vs 0.9%).
Dr. Thadhani told Reuters Health, “the suggestive effects we uncovered related to heart failure are worth studying further. A study of patients at risk for or history of heart failure but with normal ejection fraction followed for 1-2 years would be an ideal target population.”
Drs. Stefan D. Anker and Stephan von Haehling of Charite Campus Virchow-Klinikum in Berlin, Germany, who wrote the linked commentary, agree that more study is needed. The PRIMO trial “needs to be followed by a larger trial adequately powered to assess clinical end points such as cardiac-related hospitalizations, dialysis events, and mortality,” they write.
“The deciding factor for whether to prescribe paricalcitol (vitamin D) for patients with CKD should be based on improvement in important clinical outcomes rather than other end points,” they say.
Drs. Anker and von Haehling also say a “concerning” finding in the PRIMO trial was that kidney function deteriorated significantly in this population of patients with CKD taking paricalcitol. There was an average decline of 4.6 mL with paricalcitol vs placebo (p<0.001) by the creatinine-based method and an average decline of 5.6 mL vs placebo (p=0.06) by the cystatin C-based method.
They note, however, at baseline, the estimated GFR showed a difference of about 5 mL/min, with lower values in the group that received paricalcitol. It’s not possible to determine whether the two observations are linked, although more patients in the paricalcitol than placebo group started dialysis during the study (6 patients vs 1 patient; p=0.12).
The PRIMO study was funded by an investigator-initiated grant from Abbott Laboratories.
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