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

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 (h15 826, and 0.091 quality-adjusted life years gained per patient) and the ACE DD group (h105 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.

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

“…During about 3 years treatment of Japanese patients with a combination of ACE inhibitors and angiotensin receptor antagonists in carriers of II and ID genotypes proteinurea decreased (35). In contrast, in a large study among Italian patients during 10 years treatment a greater health benefit of ACE inhibitors in carriers of DD genotype compared with ID or II genotypes has been observed (36). It has been demonstrated that T2DM patients with normoor micro-albuminuria carrying I allele had a better response to ACE inhibitor therapy compared to those patients with D allele.…”

Pharmacogenetics and Metabolism: Past, Present and Future

“…In general, studies have shown that PGx is potentially cost-effective under certain circumstances (Carlson et al 2009;Vegter et al 2009;Meckley et al 2010). Some authors consider that findings showing non-robust benefit of PGx testing are due to limited knowledge of its therapeutic application since access to technology and genotyping expenses are no longer limiting factors.…”

Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients

“…The cost of the genetic screening test for the CCR5D32 polymorphism was based on PCR and included staff costs [36]. The price of hsCRP screening was based on Dutch laboratory prices.…”

“…In this context, the threshold analysis showed that even modest pharmacological effectiveness would result in a treatment strategy that is good value for money. A similar approach has recently been taken in analyzing the potential cost-effectiveness of alternative treatments for patients with chronic kidney disease resistant to angiotensin I-converting enzyme inhibitors due to angiotensin I-converting enzyme (insertion/deletion) polymorphisms [36]. Finally, the robustness of the cost-effectiveness estimate depends on whether or not pharmacologically Threshold analysis on the influence of CCR5 blocking therapy costs and effectiveness on the cost-effectiveness of a screen and treat strategy.…”