Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model
BackgroundPatients 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 com...
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| Format: | Article |
| Language: | English |
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Wiley
2016-03-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.115.002688 |
| _version_ | 1811334192919740416 |
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| author | Rohit M. Oemrawsingh K. Martijn Akkerhuis Laura C. Van Vark W. Ken Redekop Goran Rudez Willem J. Remme Michel E. Bertrand Kim M. Fox Roberto Ferrari A.H. Jan Danser Moniek de Maat Maarten L. Simoons Jasper J. Brugts Eric Boersma |
| author_facet | Rohit M. Oemrawsingh K. Martijn Akkerhuis Laura C. Van Vark W. Ken Redekop Goran Rudez Willem J. Remme Michel E. Bertrand Kim M. Fox Roberto Ferrari A.H. Jan Danser Moniek de Maat Maarten L. Simoons Jasper J. Brugts Eric Boersma |
| author_sort | Rohit M. Oemrawsingh |
| collection | DOAJ |
| description | BackgroundPatients 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 ResultsClinical, 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. ConclusionsBoth 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. |
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| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T17:04:13Z |
| publishDate | 2016-03-01 |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-6824d0c793a749909c8ab7e5d2500d7a2022-12-22T02:38:31ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-03-015310.1161/JAHA.115.002688Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk ModelRohit M. Oemrawsingh0K. Martijn Akkerhuis1Laura C. Van Vark2W. Ken Redekop3Goran Rudez4Willem J. Remme5Michel E. Bertrand6Kim M. Fox7Roberto Ferrari8A.H. Jan Danser9Moniek de Maat10Maarten L. Simoons11Jasper J. Brugts12Eric Boersma13Thoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsThoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsThoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsInstitute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The NetherlandsThoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsSTICARES Cardiovascular Research Foundation, Rhoon, The NetherlandsLille Heart Institute, Lille, FranceNational Heart and Lung Institute, Imperial College and ICMS, Royal Brompton Hospital, London, United KingdomDepartment of Cardiology and LTTA Center, University Hospital of Ferrara and Salvatore Maugeri Foundation, IRCCS, Lumezzane, ItalyDepartment of Pharmacology, Erasmus MC, Rotterdam, The NetherlandsDepartment of Hematology, Erasmus MC, Rotterdam, The NetherlandsThoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsThoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsThoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute COEUR, Rotterdam, The NetherlandsBackgroundPatients 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 ResultsClinical, 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. ConclusionsBoth 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.https://www.ahajournals.org/doi/10.1161/JAHA.115.002688angiotensin‐converting enzyme inhibitorcoronary artery diseaseindividualized therapypharmacogeneticsrisk model |
| spellingShingle | Rohit M. Oemrawsingh K. Martijn Akkerhuis Laura C. Van Vark W. Ken Redekop Goran Rudez Willem J. Remme Michel E. Bertrand Kim M. Fox Roberto Ferrari A.H. Jan Danser Moniek de Maat Maarten L. Simoons Jasper J. Brugts Eric Boersma Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiotensin‐converting enzyme inhibitor coronary artery disease individualized therapy pharmacogenetics risk model |
| title | Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model |
| title_full | Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model |
| title_fullStr | Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model |
| title_full_unstemmed | Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model |
| title_short | Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model |
| title_sort | individualized angiotensin converting enzyme ace inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants the perindopril genetic pergene risk model |
| topic | angiotensin‐converting enzyme inhibitor coronary artery disease individualized therapy pharmacogenetics risk model |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.115.002688 |
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