دورية أكاديمية
Individualized angiotensin-converting enzyme (ACE)-inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants: The PERindopril GENEtic (PERGENE) risk model
| العنوان: | Individualized angiotensin-converting enzyme (ACE)-inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants: The PERindopril GENEtic (PERGENE) risk model |
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| المؤلفون: | Oemrawsingh, R.M. (Rohit), Akkerhuis, K.M. (K. Martijn), Vark, L.C. (Laura) van, Redekop, W.K. (Ken), Rudež, G. (Goran), Remme, W.J. (Willem), Bertrand, M.E. (Michel), Fox, K.M. (Kim), Ferrari, R. (Roberto), Danser, A.H.J. (Jan), Maat, M.P.M. (Moniek) de, Simoons, M.L. (Maarten), Brugts, J.J. (Jasper), Boersma, H. (Eric) |
| المصدر: | Journal of the American Heart Association vol. 5 no. 3 |
| سنة النشر: | 2015 |
| المجموعة: | RePub - Publications from Erasmus University, Rotterdam |
| مصطلحات موضوعية: | pharmacogenetics, angiotensin-converting enzyme inhibitor, Coronary artery disease, Individualized therapy, Risk model |
| الوصف: | Background-Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. Methods and Results-Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective. Conclusions--Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://repub.eur.nl/pub/94950Test; urn:hdl:1765/94950 |
| DOI: | 10.1161/JAHA.115.002688 |
| الإتاحة: | https://doi.org/10.1161/JAHA.115.002688Test https://repub.eur.nl/pub/94950Test |
| رقم الانضمام: | edsbas.C1397777 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/JAHA.115.002688 |
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