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The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis.
Nephrol Dial Transplant. 2017 01 01; 32(1):111-125.ND

Abstract

Background

It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD).

Methods

We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD.

Results

Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies).

Conclusion

Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful.

Authors+Show Affiliations

Department of Epidemiology & Biostatistics, Western University, London, ON, Canada.Department of Epidemiology & Biostatistics, Western University, London, ON, Canada.Department of Epidemiology & Biostatistics, Western University, London, ON, Canada. London Health Sciences Centre, Division of Nephrology, Western University, London, ON, Canada.Department of Epidemiology & Biostatistics, Western University, London, ON, Canada.Department of Epidemiology & Biostatistics, Western University, London, ON, Canada. London Health Sciences Centre, Division of Nephrology, Western University, London, ON, Canada.Department of Epidemiology & Biostatistics, Western University, London, ON, Canada. Centre for Medical Evidence, Decision Integrity & Clinical Impact (MEDICI), Department of Anesthesia & Perioperative Medicine, Western University, London, ON, Canada.

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

27651467

Citation

Habbous, Steven, et al. "The Efficacy and Safety of Sevelamer and Lanthanum Versus Calcium-containing and Iron-based Binders in Treating Hyperphosphatemia in Patients With Chronic Kidney Disease: a Systematic Review and Meta-analysis." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 32, no. 1, 2017, pp. 111-125.
Habbous S, Przech S, Acedillo R, et al. The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant. 2017;32(1):111-125.
Habbous, S., Przech, S., Acedillo, R., Sarma, S., Garg, A. X., & Martin, J. (2017). The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 32(1), 111-125. https://doi.org/10.1093/ndt/gfw312
Habbous S, et al. The Efficacy and Safety of Sevelamer and Lanthanum Versus Calcium-containing and Iron-based Binders in Treating Hyperphosphatemia in Patients With Chronic Kidney Disease: a Systematic Review and Meta-analysis. Nephrol Dial Transplant. 2017 01 1;32(1):111-125. PubMed PMID: 27651467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis. AU - Habbous,Steven, AU - Przech,Sebastian, AU - Acedillo,Rey, AU - Sarma,Sisira, AU - Garg,Amit X, AU - Martin,Janet, PY - 2016/03/29/received PY - 2016/07/13/accepted PY - 2016/9/22/pubmed PY - 2017/9/28/medline PY - 2016/9/22/entrez KW - chronic kidney disease KW - hyperphosphatemia KW - lanthanum KW - sevelamer KW - systematic review SP - 111 EP - 125 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 32 IS - 1 N2 - Background: It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). Methods: We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD. Results: Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies). Conclusion: Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/27651467/The_efficacy_and_safety_of_sevelamer_and_lanthanum_versus_calcium_containing_and_iron_based_binders_in_treating_hyperphosphatemia_in_patients_with_chronic_kidney_disease:_a_systematic_review_and_meta_analysis_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfw312 DB - PRIME DP - Unbound Medicine ER -