Cost-effectiveness of pharmacogenetic testing to predict treatment response to angiotensin-converting enzyme inhibitor

Objective This study aimed to assess the potential cost-effectiveness of testing patients with nephropathies for the I/D polymorphism before starting angiotensin-converting enzyme (ACE) inhibitor therapy, using a 3-year time horizon and a healthcare perspective. Methods We used a combination of a decision analysis and Markov modeling technique to evaluate the potential economic value of this pharmacogenetic test by preventing unfavorable treatment in patients with nephropathies. The estimation of the predictive value of the I/D polymorphism is based on a systematic review showing that DD carriers tend to respond well to ACE inhibitors, while II carriers seem not to benefit adequately from this treatment. Data on the ACE inhibitor effectiveness in nephropathy were derived from the REIN (Ramipril Efficacy in Nephropathy) trial. We calculated the number of patients with end-stage renal disease (ESRD) prevented and the differences in the incremental costs and incremental effect expressed as life-years free of ESRD. A probabilistic sensitivity analysis was conducted to determine the robustness of the results. Results Compared with unselective treatment, testing patients for their ACE genotype could save 12 patients per 1000 from developing ESRD during the 3 years covered by the model. As the mean net cost savings was &U20AC;356 000 per 1000 patient-years, and 9 life-years free of ESRD were gained, selective treatment seems to be dominant. Conclusion The study suggests that genetic testing of the I/D polymorphism in patients with nephropathy before initiating ACE therapy will most likely be cost-effective, even if the risk for II carriers to develop ESRD when treated with ACE inhibitors is only 1.4% higher than for DD carriers. Further studies, however, are required to corroborate the difference in treatment response between ACE genotypes, before genetic testing can be justified in clinical practice.

[1]  J. Steurer,et al.  Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy? – A systematic review , 2005, Current controlled trials in cardiovascular medicine.

[2]  J. Emery,et al.  How can the evaluation of genetic tests be enhanced? Lessons learned from the ACCE framework and evaluating genetic tests in the United Kingdom , 2005, Genetics in Medicine.

[3]  Andrew Briggs,et al.  Probabilistic analysis of cost-effectiveness models: statistical representation of parameter uncertainty. , 2005, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[4]  H. Krumholz,et al.  National Patterns of Use and Effectiveness of Angiotensin-Converting Enzyme Inhibitors in Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction , 2004, Circulation.

[5]  Johan L Severens,et al.  Discounting health outcomes in economic evaluation: the ongoing debate. , 2004, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[6]  D. Sica ACE inhibitor intolerance and lessons learned from the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) trials. , 2004, Congestive heart failure.

[7]  S. Yusuf,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting enzyme inhibitors: the CHARM-alternative trial , 2004 .

[8]  A. Hofman,et al.  Pharmacoeconomic evaluation of testing for angiotensin-converting enzyme genotype before starting beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor therapy in men. , 2004, Pharmacogenetics.

[9]  K. Borch-Johnsen,et al.  Hypertension in people with Type 2 diabetes: knowledge‐based diabetes‐specific guidelines , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[10]  Karl Swedberg,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial , 2003, The Lancet.

[11]  Milton C Weinstein,et al.  Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices--Modeling Studies. , 2003, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[12]  Giuseppe Remuzzi,et al.  Nephropathy in Patients with Type 2 Diabetes , 2002 .

[13]  Giuseppe Remuzzi,et al.  Clinical practice. Nephropathy in patients with type 2 diabetes. , 2002, The New England journal of medicine.

[14]  J. Kvetny,et al.  Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus. , 2001, QJM : monthly journal of the Association of Physicians.

[15]  G. Remuzzi,et al.  Ramipril prolongs life and is cost effective in chronic proteinuric nephropathies. , 2001, Kidney international.

[16]  C. Schmid,et al.  Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. , 2001, Annals of internal medicine.

[17]  E. Salido,et al.  Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism. , 2000, Kidney international.

[18]  G. Remuzzi,et al.  Chronic proteinuric nephropathies. II. Outcomes and response to treatment in a prospective cohort of 352 patients: differences between women and men in relation to the ACE gene polymorphism. Gruppo Italiano di Studi Epidemologici in Nefrologia (Gisen) , 2000, Journal of the American Society of Nephrology : JASN.

[19]  G. Remuzzi,et al.  ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1. , 2000, Kidney international.

[20]  G. Navis,et al.  Angiotensin-converting enzyme gene I/D polymorphism and renal disease , 1999, Journal of Molecular Medicine.

[21]  G. Remuzzi,et al.  Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial , 1998, The Lancet.

[22]  P. Talmud,et al.  Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM. , 1998, Diabetes.

[23]  G. Mayer,et al.  Angiotensin-Converting Enzyme Gene Polymorphism Determines the Antiproteinuric and Systemic Hemodynamic Effect of Enalapril in Patients with Proteinuric Renal Disease , 1998, Kidney and Blood Pressure Research.

[24]  M J Buxton,et al.  Modelling in economic evaluation: an unavoidable fact of life. , 1997, Health economics.

[25]  X. Jeunemaître,et al.  Does long‐term angiotensin converting enzyme inhibition affect the concentration of tissue‐type plasminogen activator‐plasminogen activator inhibitor‐1 in the blood of patients with a previous myocardial infarction , 1997, Coronary artery disease.

[26]  F. Valderrábano,et al.  Report on management of renal failure in Europe, XXIV, 1993. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[27]  J. Ehrich,et al.  Report on management of renal failure in Europe, XXIII. , 1994, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[28]  J R Beck,et al.  Markov Models in Medical Decision Making , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[29]  P Corvol,et al.  An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. , 1990, The Journal of clinical investigation.