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

Pharmacogenet Genomics. 2009 Sep;19(9):695-703. doi: 10.1097/FPC.0b013e3283307ca0.

Abstract

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 (euro15 826, and 0.091 quality-adjusted life years gained per patient) and the ACE DD group (euro105 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / economics*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cost-Benefit Analysis
  • Humans
  • Kidney Failure, Chronic / economics*
  • Kidney Failure, Chronic / genetics*
  • Markov Chains
  • Mutagenesis, Insertional
  • Peptidyl-Dipeptidase A / genetics*
  • Placebo Effect
  • Polymorphism, Genetic*
  • Quality of Life
  • Quality-Adjusted Life Years
  • Renal Dialysis
  • Sequence Deletion

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • ACE protein, human
  • Peptidyl-Dipeptidase A