Cost–Effectiveness of Angiotensin-converting Enzyme Inhibitors in Nondiabetic Advanced Renal Disease

Charles Christian Adarkwah; Afschin Gandjour


Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(2):215-223. 

In This Article

Abstract and Introduction


Background: National and international clinical guidelines do not consistently recommend treating nondiabetic proteinuric patients with advanced renal disease with an angiotensin-converting enzyme (ACE) inhibitor.
Objective: To determine the cost–effectiveness of ACE inhibitor therapy in nondiabetic proteinuric patients with advanced renal disease in Germany.
Methods: Two strategies were compared: treating patients with advanced renal disease with an ACE inhibitor and no ACE inhibitor treatment. A lifetime Markov decision model was developed using published data on costs and health outcomes and simulated the progression of renal disease with costs and benefits discounted at 3%. A statutory health insurance perspective was adopted.
Results: In the base-case analysis, ACE inhibitor treatment is associated with lower costs and higher benefit and therefore dominates the no-treatment strategy. A probabilistic sensitivity analysis demonstrates that the probability of savings is 80%.
Conclusion: ACE inhibitor treatment for nondiabetic patients with advanced renal disease is highly cost effective.


End-stage renal disease (ESRD) is defined by the need for long-term dialysis or renal transplantation.[1] It is a final outcome of advanced renal disease, which is defined as a serum creatinine level of ≥3.0 mg/dl. The prevalence of ESRD has increased progressively in the few past decades in the developed world.[2] In Germany, for example, more than 90,000 patients currently receive renal replacement therapy.[2] The economic burden is considerable – in Germany, the cost of ESRD treatment is approximately €45,000 per patient per year.[3]

Angiotensin-converting enzyme (ACE) inhibitors slow down the progression from mild-to-moderate chronic kidney disease (CKD; with a serum creatinine level of 1.5–3.0 mg/dl) to ESRD in nondiabetic patients with hypertension.[4–6] ACE inhibitors have also proved to be cost effective in this patient population. In the USA, for example, benazepril treatment improves health and lowers costs, as modeled over a 7-year period.[7]

In patients with advanced renal disease (serum creatinine levels of ≥3.0 mg/dl), physicians may be reluctant to use ACE inhibitors owing to concerns that potassium levels or serum creatinine will rise.[8,9] Side effects and risks of ACE inhibitor therapy are well described in patients with chronic renal disease. These risks include cough, hyperkalemia, mild reduction in glomerular filtration rate in patients with parenchymal renal disease and acute renal failure in patients with bilateral renal artery stenosis or volume depletion.[10–13] A placebo-controlled randomized controlled trial (RCT) by Hou et al. demonstrated that ACE inhibitors can be used safely in this patient population;[1] in the 8-week run-in period, only four out of 281 patients with a serum creatinine above level 3 mg/ml had to be excluded because of hyperkalemia. Of the 224 patients who underwent randomization, the incidence of hyperkalemia was similar among patients who received an ACE inhibitor and those who received placebo.

The RCT by Hou et al. also demonstrated that ACE inhibitor therapy has a renoprotective effect in this patient population,[1] thus confirming the result of a small prior RCT.[14] Hou et al. demonstrated that the renal protective effect of ACE inhibitors in patients with advanced CKD is not only due to their antihypertensive action as the reduction in the rate of progression changed little after correction for blood pressure.[1] Although more than 90% of patients in this study population suffered from hypertension (baseline blood pressure of >150/85 mmHg), these patients did not suffer from hypertensive kidney disease as the main cause of their renal failure. In approximately 60%, glomerular disease was the main cause.[1]

The cost–effectiveness of providing ACE inhibitors in this patient population has yet to be evaluated. Therefore, the aim of this article was to determine the cost–effectiveness of ACE inhibitor therapy in nondiabetic patients with advanced renal disease (serum creatinine level above 3.0 mg/dl) and proteinuria, based on a meta-analysis of the RCTs by Ihle et al.[14] and Hou et al.[1]


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