Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy

Background: Structured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy. Methods: A systematic literature search was performed in MEDLINE and EMBASE for the period from November 1, 1999 to Oct 31, 2011. Two reviewers independently assessed the quality of the articles included and extracted data. All cost-effectiveness results were converted to 2011 Euros. Results: Up to October 2011, 434 articles were identified. After full-text checking and quality assessment, 30 articles were finally included in this review involving 39 study settings. All 6 ACEIs studies were literature-based evaluations which synthesized data from different sources. Other 33 studies were directed at ARBs and were designed based on specific trials. The Markov model was the most common decision analytic method used in the evaluations. From the cost-effectiveness results, 37 out of 39 studies indicated either ACEIs or ARBs were cost-saving comparing with placebo/conventional treatment, such as amlodipine. A lack of evidence was assessed for valid direct comparison of cost-effectiveness between ACEIs and ARBs. Conclusion: There is a lack of direct comparisons of ACEIs and ARBs in existing economic evaluations. Considering the current evidence, both ACEIs and ARBs are likely cost-saving comparing with conventional therapy, excluding such RAAS inhibitors. Background Approximately one fourth to one third of patients with diabetes mellitus develop renal manifestations [1-4]. Clinical stages of diabetic nephropathy are generally categorized into stages based on the values of urinary albumin excretion: microalbuminuria (MiA) and macroalbuminuria (MaA) [5]. The prevalence of MiA and MaA in type 2 diabetes is as high as 37–40% in western countries and 57.4–59.8% in Asian countries [6-8]. 20–40% of type 2 diabetic patients with MiA progress to overt nephropathy, * Correspondence: y.huang02@umcg.nl Department of Pharmacy, Unit of Pharmaco Epidemiology & Pharmaco Economics, University of Groningen, Groningen, The Netherlands Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Full list of author information is available at the end of the article © 2014 Huang et al.; licensee BioMed Central Commons Attribution License (http://creativec reproduction in any medium, provided the or and by 20 years after onset of overt nephropathy, about 20% will have progressed to end-stage renal diseases (ESRD) [9]. Because of the large prevalence, diabetes has become the most common single cause of ESRD in the U.S. and Europe [10,11]. As therapies and interventions for coronary artery disease continue to improve, more patients with type 2 diabetes may be expected to survive long enough to develop renal failure. In developed countries, ESRD is a major cost driver for health-care systems, with annual growth of dialysis programs ranging between 6% and 12% over the past two decades and continuing to grow, particularly in developing countries [12]. Although there are no definitive cure solutions, there is good evidence that adequate treatment can delay or prevent the progress of diabetic nephropathy including strict control of glycaemia, early Ltd. This is an open access article distributed under the terms of the Creative ommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and iginal work is properly cited. Huang et al. BMC Nephrology 2014, 15:15 Page 2 of 17 http://www.biomedcentral. com/1471-2369/15/15 treatment of hypertension, dietary protein restriction and lipid-lowering therapy [13]. Targeting renin–angiotensin–aldosterone system (RAAS) is the most effective way to delay renal disease progression. Treatment guidelines therefore recommended angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as the first-choice agents for treating nephropathy in diabetic patients [14]. Both ACEIs and ARBs target the RAAS and have proven their renal protective effects in diabetic patients in various clinical trials. One disadvantage of ACEIs [15-17] in comparison with ARBs is the higher risk of dry cough while significant differences in effectiveness between these two drug classes have not been shown convincingly although ARBs have been more thoroughly investigated in controlled settings in the recent decade providing relatively high levels of evidence. Often clinical practice guidelines recommend both ACEIs and ARBs in diabetic patients with or even without (micro)albuminuria [18]. Pharmacoeconomic evaluations of ACEIs and ARBs have been widely applied based on clinical trials’ results. The pharmacoeconomic results of ARBs have been reviewed previously [19-26]. ARBs were suggested to be cost saving in type 2 diabetic patients with nephropathy versus conventional therapy, largely due to the high costs of treatment of ESRD. However, a systematic review of costTable 1 Search terms for systematic review Search terms MEDLINE Drug Mesh: Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; TIAB (Title and Abstract): ACEIs; ARBs; ACEI; ARB; ren angiotensin system inhibitor*; renin angiotensin aldosterone system inhibitor*; ACE inhibitor*; RAS inhibitor*; RAAS inhibitor*; angiotensin converting enzyme inhibitor*; renin angiotensin system inhibitor* angiotensin receptor blocker*; Losartan; Candesartan; Valsartan; Irbesartan; Telmisartan; Eprosartan; Olmesart Azilsartan; Benazepril; Captopril; Enalapril; Fosinopril; Lisinopril; Moexipril; Perindopril; Quinapril; Ramipril; Trandolapril Diabetic Nephropathy (DN) Mesh: Diabetes Mellitus, Type 2; Diabetic Nephropath Kidney Failure, Chronic; TIAB: diabetic nephropathy*; diabetic renal disease*; diabetic kidney disease*; Economic Evaluation (EE) Mesh: Economics, Pharmaceutical; Costs and Cost Analy Drug Costs; Cost Savings; Cost of Illness; Cost-Benefit Ana TIAB: cost effect*; cost utility; cost benefit*; economic evaluation*; cost analys* Search Strategy (“Drug Term 1”[Mesh] OR “Drug Term 2”[TIAB] .) AN (“DN Term 1”[Mesh] OR “DN Term 2”[TIAB] .) AND (“EE Term 1”[Mesh] OR “EE Term 2”[TIAB] .) a: An asterisk (*) following the word is the wildcard character, which means to sear can be found in MEDLINE. effectiveness results of ACEIs in type 2 diabetic patients with renal disease is still lacking. In addition, the need of a structured pharmacoeconomic comparison of the ACEIs with ARBs is pointed out by some researchers [21,26]. The aim of this study is to address the similarities and differences in cost-effectiveness analyses for both ACEIs and ARBs in type 2 diabetic patients with nephropathy. In particular, three objectives are addressed: 1) to summarize the cost-effectiveness of ACEIs; 2) to update the costeffectiveness of ARBs; 3) to compare the characteristics of different economic evaluations and analyze potential differences and similarities in the cost-effectiveness between the two drug classes reviewed.