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ACE Inhibitors or ARBs: Which to Prescribe?

Many dialysis patients, including patients on frequent home hemodialysis, have been diagnosed with heart failure. In one large study, 31% of patients who initiated home hemodialysis already had heart failure.1 One of the cornerstones of pharmacologic therapy for heart failure is renin-angiotensin system blockade, which may be achieved with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). In most clinical practice guidelines, ACE inhibitors are recommended as first-line therapy, while ARBs are recommended as a second option for patients who cannot tolerate an ACE inhibitor, typically because of a dry, persistent cough and atypically because of angioedema.2  Perhaps as a manifestation of this, the use of ACE inhibitors exceeds the use of ARBs by a ratio of roughly 2 to 1 among dialysis patients who are enrolled in Medicare Part D.3

In dialysis-dependent chronic kidney disease, we lack large randomized clinical trials that definitively prove the efficacy of either ACE inhibitors or ARBs for the treatment of heart failure, although several small trials have suggested benefit.4 Despite this uncertainty, we know an important detail about the pharmacokinetics of these drug classes: aside from fosinopril, ACE inhibitors are cleared by hemodialysis, whereas ARBs are not. Thus, there is rationale for the preferential use of ARBs in dialysis patients with appropriate indications.

In an exhaustive review of randomized clinical trials in the April 3, 2018 issue of the Journal of the American College of Cardiology, Messerli and colleagues found that risks of clinical outcomes (e.g., cardiovascular death, myocardial infarction, and stroke) were similar with ACE inhibitors and ARBs, but that the risk of drug withdrawal due to adverse events was 28% lower with ARBs versus ACE inhibitors (hazard ratio of drug withdrawal, 0.72; 95% confidence interval, 0.65-0.81).5

The authors concluded that “risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.” 5

Today in the United States, many ARBs, including candesartan, losartan, and the relatively oft-used valsartan, are available in generic formulations. Considering the review by Messerli and colleagues, as well as the added nuance of drug dialyzability, it seems reasonable to consider whether dialysis patients with heart failure should be prescribed ARBs as first-line therapy.

 

  1. Weinhandl, E.D., Gilbertson, D.T., Collins, A.J. Mortality, hospitalization, and technique failure in daily home hemodialysis and matched peritoneal dialysis patients: a matched cohort study. Am J Kidney Dis. 2016;67:98–110.
  2. Yancy, C.W., et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;CIR.0b013e31829e8776, originally published June 5, 2013.
  3. Frankenfield, D.L., et al. Utilization and costs of cardiovascular disease medications in dialysis patients in Medicare Part D. Am J Kidney Dis. 2012 May;59(5):670-81.
  4. Inrig, J.K. Antihypertensive Agents in Hemodialysis Patients: A Current Perspective. Semin Dial. 2010;23(3):290-297.
  5. Messerli, F.H., Bangalore, S., Bavishi, C., Stefano F. Rimoldi, S.F. Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use? J Am Coll Cardiol. 2018;71(13):1474-1482.
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Eric Weinhandl, PhD, MS

Adjunct Assistant Professor
University of Minnesota College of Pharmacy

Clinical Epidemiologist and Statistician
NxStage Medical, Inc.

Eric Weinhandl is an epidemiologist with about 14 years of research experience in chronic kidney disease, mostly regarding dialysis and pharmaceuticals. Eric worked at the United States Renal Data System (USRDS) Coordinating Center between 2004 and 2014 and has conducted studies with Amgen, Baxter, DaVita, NxStage, Sigma Tau, and the Peer Kidney Care Initiative.

Articles by Eric Weinhandl, PhD, MS
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