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Cost-effectiveness of ACE inhibitor therapy to prevent dialysis in nondiabetic nephropathy: influence of the ACE insertion/deletion polymorphism

Vegter, Stefana b; Perna, Annalisad; Hiddema, Wâtsea; Ruggenenti, Pierod,e; Remuzzi, Giusepped,e; Navis, Gerjana b; Postma, Maarten J.a c

doi: 10.1097/FPC.0b013e3283307ca0

Introduction End-stage renal disease is associated with high health-care costs and low quality of life compared with chronic kidney disease. The renoprotective effectiveness of angiotensin-converting enzyme inhibitors (ACEi) is largely determined by the ACE insertion/deletion (I/D) polymorphism. We determined the cost-effectiveness of ACEi therapy in nondiabetic nephropathy for the ACE II/ID and for the ACE DD genotype separately. Furthermore, we considered a selective screen-and-treat strategy in which patients are prescribed alternative, more effective, therapy based on their ACE (I/D) polymorphism.

Methods Time-dependent Markov models were constructed; cohorts of 1000 patients were followed for 10 years. Data were mainly gathered from the Ramipril Efficacy In Nephropathy trial. Both univariate and probabilistic sensitivity analyses were performed.

Results ACEi therapy dominated placebo in both the ACE II/ID group (€15 826, and 0.091 quality-adjusted life years gained per patient) and the ACE DD group (€105 104 and 0.553 quality-adjusted life years gained). Sensitivity analyses showed 30.2% probability of ACEi being not cost-effective in the ACE II/ID group, against an almost 100% probability of cost-effectiveness in the ACE DD group. A selective screen-and-treat strategy should incorporate an alternative therapy for patients with the ACE II/ID genotype with an at least 9.1% increase in survival time compared with ACEi therapy to be cost-effective. Sensitivity analyses show that higher effectiveness and lower costs of the alternative therapy improve the cost-effectiveness of a screening strategy.

Conclusion ACEi therapy is a cost-saving treatment compared with placebo in nondiabetic nephropathy, irrespective of ACE (I/D) genotype. However, ACEi therapy saved more costs and more health gains were achieved in the ACE DD genotype than in the ACE II/ID genotype. An alternative treatment featuring a modest increase in effectiveness compared with ACEi therapy for patients with the ACE II/ID genotype can be incorporated in a cost-effective or even cost-saving screen-and-treat strategy.

Departments of aPharmacy, Unit of PharmacoEpidemiology and PharmacoEconomics (PE2), University of Groningen

bInternal Medicine, Division of Nephrology

cEpidemiology, University Medical Centre Groningen (UMCG), Groningen, The Netherlands

dClinical Research Centre for Rare Diseases ‘Aldo e Cele Daccò’, Mario Negri Institute for Pharmacological Research, Bergamo, Italy

eUnit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy

Correspondence to Stefan Vegter, MSc, Department of Pharmacy, Unit of PharmacoEpidemiology and PharmacoEconomics (PE2), Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands

Tel: +31 50 363 8204; fax: +31 50 363 2772; e-mail:

Received 11 November 2008 Accepted 6 July 2009

© 2009 Lippincott Williams & Wilkins, Inc.