The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis.

Abstract

BACKGROUND:

This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone.

METHODS:

Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30- 180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 μg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52.

RESULTS:

Median (P10, P90) Agatston CAC scores increased 24% (-22%, 119%) in the cinacalcet group and 31% (-9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (-12%, 105%) and 30% (-6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve.

CONCLUSIONS:

In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

• Authors: Paolo Raggi, Glenn M Chertow, Pablo Urena Torres, Botond Csiky, Agostino Naso, Kaldun Nossuli, Moustafa Moustafa, William G Goodman, Nicole Lopez, Gerry Downey, Bastian Dehmel, Jürgen Floege, ADVANCE Study Group
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 26 Issue 4 Pg. 1327-39 (Apr 2011) ISSN: 1460-2385 [Electronic] England
• PMID: 21148030 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Naphthalenes
• Vitamins
• Vitamin D
• Cinacalcet

Topics

• Adult
• Calcinosis (drug therapy, etiology)
• Cinacalcet
• Coronary Artery Disease (drug therapy, etiology)
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Humans
• Hyperparathyroidism, Secondary (drug therapy, etiology)
• Kidney Failure, Chronic (complications, therapy)
• Male
• Middle Aged
• Naphthalenes (therapeutic use)
• Prognosis
• Prospective Studies
• Renal Dialysis
• Vitamin D (therapeutic use)
• Vitamins (therapeutic use)