Rates of Hyperkalemia after Publication of the Randomized Aldactone Evaluation Study
David N. Juurlink, M.D., Ph.D., Muhammad M. Mamdani, Pharm.D., M.P.H., Douglas S. Lee, M.D., Alexander Kopp, B.A., Peter C. Austin, Ph.D., Andreas Laupacis, M.D., and Donald A. Redelmeier, M.D.
Background The Randomized Aldactone Evaluation Study (RALES)demonstrated that spironolactone significantly improves outcomesin patients with severe heart failure. Use of angiotensin-convertingenzyme(ACE) inhibitors is also indicated in these patients. However,life-threatening hyperkalemia can occur when these drugs areused together.
Methods We conducted a population-based time-series analysisto examine trends in the rate of spironolactone prescriptionsand the rate of hospitalization for hyperkalemia in ambulatorypatients before and after the publication of RALES. We linkedprescription-claims data and hospital-admission records formore than 1.3 million adults 66 years of age or older in Ontario,Canada, for the period from 1994 through 2001.
Results Among patients treated with ACE inhibitors who had recentlybeen hospitalized for heart failure, the spironolactone-prescriptionrate was 34 per 1000 patients in 1994, and it increased immediatelyafter the publication of RALES, to 149 per 1000 patients bylate 2001 (P<0.001). The rate of hospitalization for hyperkalemiarose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patientsin 2001 (P<0.001), and the associated mortality rose from0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As comparedwith expected numbers of events, there were 560 (95 percentconfidence interval, 285 to 754) additional hyperkalemia-relatedhospitalizations and 73 (95 percent confidence interval, 27to 120) additional hospital deaths during 2001 among older patientswith heart failure who were treated with ACE inhibitors in Ontario.Publication of RALES was not associated with significant decreasesin the rates of readmission for heart failure or death fromall causes.
Conclusions The publication of RALES was associated with abruptincreases in the rate of prescriptions for spironolactone andin hyperkalemia-associated morbidity and mortality. Closer laboratorymonitoring and more judicious use of spironolactone may reducethe occurrence of this complication.
Source Information
From the Departments of Medicine (D.N.J., D.S.L., A.L., D.A.R.), Pharmacy (M.M.M.), Health Policy, Management, and Evaluation (D.N.J., M.M.M., D.S.L., P.C.A., A.L., D.A.R.), and Public Health Sciences (P.C.A.), University of Toronto; and the Institute for Clinical Evaluative Sciences (D.N.J., M.M.M., D.S.L., A.K., P.C.A., A.L., D.A.R.) both in Toronto.
Address reprint requests to Dr. Juurlink at Sunnybrook and Women's College Health Sciences Centre, G Wing 106, 2075 Bayview Ave., Toronto, ON M4N 3M5, Canada, or at dnj{at}ices.on.ca.
Hyperkalemia after the Publication of RALES
Goldfarb D. S., Newsome B. B., Warnock D. G., Witham M. D., Gillespie N. D., Struthers A. D., Cavallari L., Vaitkus P., Groo V., Juurlink D. N., Mamdani M. M., Redelmeier D. A.
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N Engl J Med 2004;
351:2448-2450, Dec 2, 2004.
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