Angiotensin-converting enzyme inhibitors andcardiovascular outcomes in patients onmaintenance hemodialysis
Tara I. Chang, MD, MS,
David Shilane, PhD,
Steven M. Brunelli, MD, MSCE,
Alfred K. Cheung, MD,
Glenn M. Chertow, MD, MPH,
and Wolfgang C. Winkelmayer, MD, MPH, ScD
Palo Alto, CA; Boston, MA; and Salt Lake City, UT
Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but thereare few data regarding their effectiveness in ESRD.
We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose andmembrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, usingproportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and thecomposite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.
In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazardratio 0.97, 95% CI 0.82-1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzymeinhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11-1.80). In thepropensity score
matched cohort, ACEI use was not significantly associated with any outcomes, including heart failurehospitalization.
In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI usemay not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in thegeneral population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease. (Am Heart J 2011;162:324-30.)
Angiotensin-converting enzyme inhibitors (ACEIs) havebeen shown to reduce mortality and cardiovascular morbidity in a variety of clinical scenarios, such aspostacute myocardial infarction or in patients with heartfailure or left ventricular dysfunction.
Persons withend-stage renal disease (ESRD) on dialysis carry anexceptionally high burden of cardiovascular disease, with45% of all deaths attributed to cardiovascular causes.
Although current national clinical practice guidelines
recommend the use of ACEIs in patients on maintenancedialysis, there are few data regarding their effectivenessfor cardiovascular disease prevention in this populationbecause randomized clinical trials of ACEIs systematically excluded patients with ESRD.Given the uncertainty surrounding the effectiveness of ACEIs in patients on maintenance hemodialysis, weconducted a secondary analysis of data from the HEMOstudy.
The HEMO study data have several advantagesover previous observational studies, in that the datacontain exceptionally detailed clinical information, allow- ing for improved case-mix adjustment, and clinicaloutcomes were rigorously adjudicated using standardizedcriteria rather than determined by administrative codes. We hypothesized that subjects receiving ACEIs at study entry would have lower risks of mortality and
Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA,
Department of Health Research and Policy, Stanford University School of Medicine, Palo Alto, CA,
Renal Division, Department of Medicine, Brigham and Women's Hospital,Harvard Medical School, Boston, MA,
Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, and
Division of Nephrology & Hypertension,University of Utah, Salt Lake City, UT.Submitted March 9, 2011; accepted May 3, 2011.Reprint requests: Tara I. Chang, MD, MS, Stanford University School of Medicine Divisionof Nephrology, 780 Welch Road, Suite 106, Palo Alto, CA 94304.E-mail:firstname.lastname@example.org 0002-8703/$ - see front matter © 2011, Mosby, Inc. All rights reserved.doi:10.1016/j.ahj.2011.05.004