Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism

Cunningham, John A.; Danese, Mark D.; Olson, Kurt; Klassen, Preston S.; Chertow, Glenn M.

doi:10.1111/j.1523-1755.2005.00596.x

Cited by 520 publications

(364 citation statements)

References 47 publications

(48 reference statements)

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“…At present, there are no reports of randomized, prospective clinical trials that have investigated the effects of such therapies on mortality in dialysis patients. As a consequence, treatment decisions have been forced to rely on results from post hoc analyses of prospective studies (cinacalcet) (16) and observational studies (vitamin D sterols) (9,32). Overall, it is clear that additional studies are necessary to confirm any associations between existing therapies for CKD-MBD and patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…The calcimimetic cinacalcet HCl reduces serum PTH, calcium, phosphorus, and Ca ϫ P in dialysis patients (13)(14)(15), and in a post hoc analysis, treatment was associated with improved clinical outcomes, including improved quality of life and reduced risk for parathyroidectomy, cardiovascular hospitalization, and fracture (16). Furthermore, in a recent small, singlearm study, treatment with cinacalcet was associated with progressive improvement in markers of bone metabolism, including bone AP (17).…”

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confidence: 99%

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Cinacalcet Lowers Serum Alkaline Phosphatase in Maintenance Hemodialysis Patients

Belozeroff¹,

Goodman²,

Ren³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: Studies suggest an association between elevated serum alkaline phosphatase (AP) and increased mortality in hemodialysis patients, but the effect of existing therapies on AP is not fully understood. We assessed the effects of cinacalcet on AP in a secondary analysis of controlled trial data.Design, setting, participants, & measurements: This was a post hoc analysis of data from three 26-wk randomized, double-blind, placebo-controlled, phase 3 trials and a 26-wk double-blind, placebo-controlled extension trial that investigated cinacalcet in secondary hyperparathyroidism treatment in dialysis patients. Hemodialysis patients (n ‫؍‬ 890) with intact parathyroid hormone >300 pg/ml and serum calcium >8.4 mg/dl received cinacalcet plus standard therapy or standard therapy alone for up to 52 wk. Total, not bone-specific, AP was assessed (proportion of cinacalcet/control subjects achieving a >20% or any AP reduction from baseline; the proportion of subjects with AP >120 U/L) at baseline; the end of titration; and study weeks 26, 42, and 52.Results: At 52 wk, a greater proportion of cinacalcet-treated patients had either a >20% (39 versus 18%) or any (58 versus 36%) AP reduction compared with control subjects, respectively. The likelihood of achieving either a >20% or any AP reduction (determined by relative proportion) was 2.33 (95% confidence interval 1.50 to 3.61) and 1.74 (95% confidence interval 1.31 to 2.31), respectively, at week 52. Cinacalcet treatment tended toward a decreased percentage of patients with AP >120 U/L (baseline, 42.6%; week 52, 30.6%) compared with control (35.0 to 48.6%, respectively).Conclusions: In this combined analysis of controlled trials of patients who were receiving hemodialysis, cinacalcet lowered total serum AP.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cinacalcet Lowers Serum Alkaline Phosphatase in Maintenance Hemodialysis Patients

Belozeroff¹,

Goodman²,

Ren³

et al. 2009

Clinical Journal of the American Society of Nephrology

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“…Prescription patterns for hemodialysis patients with secondary hyperparathyroidism have begun to vary widely since cinacalcet introduction (1)(2)(3), and the effects of these patterns on laboratory values (1-9) and clinical outcomes (10,11) have attracted attention. Before cinacalcet introduction, the only treatment option available for elevated parathyroid hormone (PTH) levels was vitamin D receptor activator (VDRA) (12).…”

Section: Introductionmentioning

confidence: 99%

Prescription Patterns and Mineral Metabolism Abnormalities in the Cinacalcet Era

Fukagawa

Fukuma

Ônishi³

et al. 2012

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives Prescription patterns for hemodialysis patients with secondary hyperparathyroidism have varied widely since market introduction of cinacalcet. This study examined associations between prescription patterns and subsequent laboratory values. Design, setting, participants, & measurements Using a Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients subcohort, 1716 prevalent hemodialysis patients (4048 sets for repeated measures between January 2008 and July 2009) with an intact parathyroid hormone (iPTH) level >180 pg/ml who used intravenous vitamin D receptor activator (VDRA) without cinacalcet were selected. Prescription patterns were defined based on cinacalcet administration (starting or not) and VDRA dosage change (decreased [<−25%], stable [−25% to 25%], or increased [>25%]). Proportion differences (PDs) were determined for decreasing iPTH levels by at least one category (<180, 180–299, 300–499, and ≥500 pg/ml) and for achieving target phosphorus (3.5–6.0 mg/dl) and calcium (8.4–10.0 mg/dl) levels, adjusting for potential confounders. Results The starting cinacalcet and increased VDRA patterns were associated with decreasing iPTH levels (PD, 0.25 and 0.13; 95% confidence intervals [95% CIs], 0.19–0.31 and 0.09–0.17, respectively); combination use had an additive association (PD, 0.34; 95% CI, 0.20–0.42). The starting cinacalcet and decreased VDRA combination was associated with simultaneously achieving target phosphorus (PD, 0.12; 95% CI: 0.04–0.20) and calcium (PD, 0.09; 95% CI, 0.01–0.17) levels. Conclusions Certain combinations of cinacalcet and VDRA were associated with decreasing iPTH and achieving targets for phosphorus and calcium. Combinations may prove advantageous versus VDRA alone in managing secondary hyperparathyroidism.

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“…Further, Cc reduced the amount of fractures and the rate of CV hospitalisation in dialysis patients. 18 The two trials the CONTROL study 19 and the OPTIMA study 20 evaluated the effects of Cc with the goal to reduce the dose of vitamin D 19 and to reach the target for iPTH 20 in patients with end-stage renal failure (ESRF).…”

Section: Introductionmentioning

confidence: 99%

Experience with Cinacalcet for Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease Stage III and IV

Forslund

Koistinen

Miettinen

2009

Clinical Medicine. Therapeutics

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Dysequilibrium in calcium and phosphate metabolism with development of secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD) stage III and IV. Dietary phosphate restrictions and calcium based oral phosphate binders have not been effective in all subjects with SHPT, and soft tissue and vascular calcifications with an increased risk of cardiovascular death related are known consequences. Treatment with the calcimimetic Cinacalcet (Cc) has contributed to a better calcium and phosphate control in patients given hemodialysis treatment. In this retrospective study we present our experience with Cc given to ten (one year) or five (two years) patients with CKD stage III and IV and SHPT not suitable for surgery. With conventional therapy target levels of intact parathyroid hormon (iPTH) are seldomly reached the reason why an iPTH value  300 ng/l was considered acceptable. Levels of iPTH decreased significantly after 3 months of Cc treatment and remained at the lower level. Plasma ionized-Ca (Ca) concentrations decreased initially but remained above 1.00 mmol/l in all but one patient. Phophate (P) levels increased to 1.41 ± 0.09 mmol/l (mean ± SE) leaving the Ca × P product unchanged. While patients with high iPTH needed high Cc doses up to 90 mg/day, some of the patients required very low doses 4.5-20 mg/day in order to achieve a decrease in iPTH levels. Only one patient reported gastric pain needing dose reduction and other adverse effects were not found. No changes in QT-time were observed. We experienced that Cc treatment was promising to control SHPT and stabilized the Ca-P balance in patients with CKD stage III and IV. Dosing may be challenging and laboratory values should be controlled often (monthly) as these patients may have variable response to Cc treatment. Due to the minimal knowledge about its effect on morbidity and mortality in the predialytic population further controlled studies are needed to confirm its efficacy and safety.

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Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism

Cited by 520 publications

References 47 publications

Cinacalcet Lowers Serum Alkaline Phosphatase in Maintenance Hemodialysis Patients

Cinacalcet Lowers Serum Alkaline Phosphatase in Maintenance Hemodialysis Patients

Prescription Patterns and Mineral Metabolism Abnormalities in the Cinacalcet Era

Experience with Cinacalcet for Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease Stage III and IV

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