CLINICAL RESEARCH: LEFT VENTRICULAR DYSFUNCTION
Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction
Areef Ishani, MD*,*,
Eric Weinhandl, MS ,
Zihong Zhao, MS,
David T. Gilbertson, PhD,
Allan J. Collins, MD, ,
Salim Yusuf, MD and
Charles A. Herzog, MD,
* Section of Nephrology, Department of Medicine, Minneapolis VAMC and the University of Minnesota, Minneapolis, Minnesota
Minneapolis Medical Research Foundation, Minneapolis, Minnesota
Divisions of Nephrology and Cardiology, Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota
Division of Cardiology, and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
Manuscript received July 27, 2004;
revised manuscript received September 21, 2004,
accepted October 4, 2004.
* Reprint requests and correspondence: Dr. Areef Ishani, Division of Nephrology (111J), Department of Medicine, Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, Minnesota 55417 (Email: isha0012{at}umn.edu).
OBJECTIVES: We aimed to investigate the impact of angiotensin-converting enzyme inhibitors (ACEIs) on hematocrit values in those with heart failure, and the relationship between incident anemia and mortality.
BACKGROUND: Prevalent anemia is an independent risk factor for morbidity and mortality in those with heart failure. Studies in patients with polycythemia have demonstrated that ACEIs are effective in lowering hematocrit values.
METHODS: We used the Studies Of Left Ventricular Dysfunction (SOLVD) database to compare the odds of developing new anemia at one year in patients who were not anemic at entry and who were randomized to enalapril or placebo. Cox proportional hazards models were utilized to determine the impact of incident and prevalent anemia on subsequent mortality.
RESULTS: Enalapril increased the odds of incident anemia (hematocrit  39% in men or 36% in women) at one year by 48% (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.20 to 1.82) in unadjusted and 56% (OR 1.56, 95% CI 1.26 to 1.93) in adjusted models. With multivariate analysis, prevalent anemia at randomization was associated with a 44% (hazard ratio [HR] 1.44, 95% CI 1.31 to 1.66) increase in all-cause mortality, whereas incident anemia after randomization was associated with a 108% increase (HR 2.08, 95% CI 1.82 to 2.38). After adjusting for incident and prevalent anemia, use of enalapril was associated with a survival benefit.
CONCLUSIONS: Enalapril was associated with increased odds of developing anemia at one year. Those with periods of time with incident anemia had the poorest survival, followed by those with prevalent anemia, then those without anemia. Enalapril was protective of overall mortality after adjusting for incident anemia and in those with prevalent anemia.
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Abbreviations and Acronyms
| | ACEI = angiotensin-converting enzyme inhibitor | | ARB = angiotensin receptor blocker | | CI = confidence interval | | HF = heart failure | | HR = hazard ratio | | NYHA = New York Heart Association | | OR = odds ratio | | SOLVD = Studies Of Left Ventricular Dysfunction |
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