Correspondence

Financial Disclosure: The authors declare that they have norelevant financial interests.

References1. Abidin MR, Spector DA, Kittur DS. Peritoneal dialysis

catheter outflow obstruction due to oviductal fimbriae: a casereport. Am J Kidney Dis. 1990;16(3):256-258.

2. Moreiras-Plaza M, Cáceres-Alvarado N. Peritoneal dialysiscatheter obstruction caused by Fallopian tube wrapping. Am JKidney Dis. 2004;44(2):e28-30.

3. Borghol M, Alrabeeah A. Entrapment of the appendix andthe fallopian tube in peritoneal dialysis catheters in two children.J Pediatr Surg. 1996;31(3):427-429.

4. Klein Z, Magen E, Fishman A, Korzets Z. Laparoscopicsalpingectomy: the definitive treatment for peritoneal dialysiscatheter outflow obstruction caused by oviductal fimbriae. J Lapa-roendosc Adv Surg Tech A. 2003;13(1):65-68.

5. Uchiyama K, Fujikawa K, Suga A, Naito K. Laparoscopicsalvage of malfunctioning peritoneal dialysis catheters caused byovarian fimbria: a case report. Hinyokika Kiyo. 2001;47(9):669-671.

© 2011 by the National Kidney Foundation, Inc.doi:10.1053/j.ajkd.2010.11.017

RESEARCH LETTER

Sevelamer Prescriptions After Reportingof the Dialysis Clinical Outcomes Revisited(DCOR) Trial Findings: An Analysis of 5,495Patients Receiving Maintenance Dialysis inOntario, CanadaTo the Editor:

A randomized controlled trial (RCT) often is accepted as thebest way to test the effects of a therapy. When an RCT shows asignificant benefit or harm, the findings can readily translateinto clinical practice.1-3 However, predicting the effect of anegative trial (one that fails to show statistically significantresults) is more problematic. We recently showed that 4D (DerDeutsche Diabetes Dialyse Studie), a negative trial of atorvasta-tin in dialysis patients, was not associated with a change in theuse of statin drugs in this population.4 We speculated thatanother negative study, the DCOR (Dialysis Clinical OutcomesRevisited) trial,5 also might have failed to influence sevelameruse in dialysis patients and therefore examined the rate ofsevelamer prescriptions before and after reporting of DCORresults.

Using Ontario’s health administrative data, we conducted aretrospective interventional analysis from January 1, 2001, toMarch 31, 2009. Ontario is Canada’s most populous province,with approximately 13 million residents who receive universalhealth coverage under the Ontario Health Insurance Plan (OHIP).Beginning in 2001, prescription drug coverage for sevelamerwas provided at a physician’s request to any patient withend-stage renal disease who on 2 occasions had serum calciumand phosphate concentrations �2.65 and �1.80 mmol/L, respec-tively, despite using a calcium-based binder. We determined thenumber of quarterly sevelamer prescriptions using the OntarioDrug Benefits (ODB) database, which has an error rate of�1%.6 We assembled a cohort of patients receiving mainte-nance dialysis using billing codes recorded in the OHIP data-base (Item S1, available as online supplementary material). Toascertain prescription drug use from the ODB database, we

limited our cohort to patients 66 years or older. We excluded

Am J Kidney Dis. 2011;57(2):352-359

cases of dialysis for acute kidney injury. Patients were removedfrom the cohort at the time of kidney transplant or death. Withinthis cohort, we determined the numbers of sevelamer prescrip-tions per 1,000 dialysis patients each quarter for 33 quarters.

Reporting of DCOR results at the American Society ofNephrology annual conference in November 2005 was ourintervention of interest. DCOR was a prospective multicenteropen-label RCT comparing sevelamer with calcium-based phos-phate binders in 2,103 patients receiving maintenance hemodi-alysis. The investigators aimed to show reductions in all-causeand cardiovascular mortality, but after 45 months of follow-up,no significant differences in these outcomes were found.5 Al-though presented first in November 2005, the trial was pub-lished in November 2007, with a secondary analysis publishedin March 2008.5,7 To assess for a change in sevelamer prescrip-tion rate after the reporting of DCOR, we applied an autoregres-sive integrated moving average model–based intervention anal-ysis to a time series of sevelamer prescriptions per 1,000patients. As a tracer outcome, we assessed the calcitriol prescrip-tion rate within the cohort, expecting that DCOR results wouldhave no impact on calcitriol prescriptions. During the 8-yearstudy period, our cohort grew from 3,528 to 5,495 patients.Table 1 lists baseline characteristics of patients enrolled inDCOR and those in our cohort. Overall, Ontario patients wereolder, less likely to have diabetes, and on dialysis therapylonger. The intervention analysis showed a significant change insevelamer prescription rate after the reporting of DCOR (Fig 1;P � 0.01). A significant change in prescription rate of the tracerdrug calcitriol was neither expected nor observed.

After DCOR results were reported, we observed a sudden haltin the increasing number of sevelamer prescriptions filled byelderly patients on dialysis therapy. We suspect that physiciansresponded strongly to the results of DCOR for a number ofreasons. First, this finding may reflect physicians’ appropriatelycautious interpretation of the subgroup analysis that suggestedimproved mortality rates in patients older than 65 years.5,7,8

Second, there were no mortality data from other studies torefute DCOR’s findings. Third, inexpensive and effective alter-native medications were readily available to treat hyperphos-phatemia. Finally, unlike statins, no evidence outside the end-stage renal disease population existed to support the use ofsevelamer.

Our study examined a large cohort of patients and ascertainedprescriptions and comorbid conditions using validated codesand reliable databases.6,9 However, our cohort was not perfectlyanalogous to the patients enrolled in DCOR. Although therewere no changes to funding for sevelamer or the procurement

Table 1. Baseline Characteristics of Patients in the DCOR Trialand Ontario Cohort

DCOR Ontario Cohorta

Sample size 2,103 5,495

Age (y) 60 � 15 76 � 7

Women (%) 45.6 43.6

Diabetes mellitus (%)b 50.2 38.0

Dialysis duration (mo) 38 � 40 50 � 46

Note: Values expressed as mean � standard deviation orpercentage unless stated otherwise.

Abbreviation: DCOR, Dialysis Clinical Outcomes Revisited.aBaseline characteristics were determined using the most

recent quarter of data (January 1, 2009, to March 31, 2009).bFor Ontario data, the diagnosis of diabetes mellitus was

determined using valid health administrative codes.

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lysis t

Correspondence

process during the study interval, immeasurable factors, such aschanges in its marketing, may have influenced our findings.Although this was a population-based study, generalization ofour findings to jurisdictions without universal prescription drugcoverage may not be appropriate. In conclusion, our studysuggests that the knowledge provided by DCOR has beentranslated into the practices of Ontario nephrologists.

Matthew A. Weir, MD,1 Arsh K. Jain, MD1

Tara Gomes, MHSc,2 David N. Juurlink, MD, PhD2,3,4

Muhammad Mamdani, PharmD, MA, MPH,2,3,4,5 Lihua Li, MSc1

Amit X. Garg, MD, PhD1,2

1University of Western OntarioLondon, Canada

2Institute for Clinical Evaluative Sciences (ICES)3Sunnybrook Health Sciences Centre

4University of Toronto5St. Michael’s Hospital

Toronto, Canada

AcknowledgementsThe corresponding author, Dr Weir, may be contacted at

mweir@uwo.ca.Support: This project was supported by the Lawson Health Re-

search Institute and the Ontario Drug Policy Research Network,which receives funding from the Ontario Ministry of Health and

Figure 1. Sevelamer prescriptions in patients on maintenance dia

Long-term Care (MOHLTC) Drug Innovation Fund. Dr Weir was

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supported by the Clinical Investigator Program Award at the Univer-sity of Western Ontario and funding from the MOHLTC. Dr Garg wassupported by a Clinician Scientist Award from the Canadian Institutesof Health Research. The Institute of Clinical Evaluative Sciences(ICES) receives funding from the MOHLTC. The opinions, results,and conclusions reported in this paper are those of the authors and areindependent from the funding sources.

Financial Disclosure: The authors declare that they have norelevant financial interests.

Supplementary MaterialItem S1: Definition of Maintenance Dialysis Patients.Note: The supplementary material accompanying this article

(doi:10.1053/j.ajkd.2010.09.025) is available at www.ajkd.org.

References1. Jackevicius CA, Anderson GM, Leiter L, Tu JV. Use of the

statins in patients after acute myocardial infarction: does evidencechange practice? Arch Intern Med. 2001;161(2):183-188.

2. Austin PC, Mamdani MM, Tu K, Jaakkimainen L. Prescrip-tions for estrogen replacement therapy in Ontario before and afterpublication of the Women’s Health Initiative Study. JAMA. 2003;289(24):3241-3242.

3. Tu K, Mamdani MM, Jacka RM, Forde NJ, Rothwell DM,Tu JV. The striking effect of the Heart Outcomes PreventionEvaluation (HOPE) on ramipril prescribing in Ontario. CMAJ.

herapy. Abbreviation: DCOR, Dialysis Clinical Outcomes Revisited.

2003;168(5):553-557.

Am J Kidney Dis. 2011;57(2):352-359

Correspondence

4. Lam NN, Jain AK, Hackam DG, et al. Results of a random-ized controlled trial on statin use in dialysis patients had noinfluence on statin prescription. Kidney Int. 2009;76:1172-1179.

5. Suki WN, Zabaneh R, Cangiano JL, et al. Effects of sevel-amer and calcium-based phosphate binders on mortality in hemo-dialysis patients. Kidney Int. 2007;72(9):1130-1137.

6. Levy AR, O’Brien BJ, Sellors C, et al. Coding accuracy ofadministrative drug claims in the Ontario Drug Benefit database.Can J Clin Pharmacol. 2003;10(2):67-71.

7. St. Peter WL, Liu J, Weinhandl E, Fan Q. A comparison ofsevelamer and calcium-based phosphate binders on mortality,

hospitalization, and morbidity in hemodialysis: a secondary analy-

Am J Kidney Dis. 2011;57(2):352-359

sis of the Dialysis Clinical Outcomes Revisited (DCOR)randomized trial using claims data. Am J Kidney Dis. 2008;51(3):445-454.

8. Winkelmayer WC, Tonelli M. Phosphate binder choice indialysis patients: a call for evidence-based rather than marketing-based clinical practice. Am J Kidney Dis. 2008;51(3):362-365.

9. Juurlink D, Preyra C, Croxford R, et al. Canadian Institute forHealth Information Discharge Abstract Database: A Validation Study.Toronto, Canada: Institute for Clinical Evaluative Sciences; 2006.

© 2011 by the National Kidney Foundation, Inc.

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