A prospective study of the impact of AGTR1 A1166C on the effects of candesartan in patients with heart failure

Author:

de Denus Simon123,Dubé Marie-Pierre124,Fouodjio René12,Huynh Thao5,LeBlanc Marie-Hélène6,Lepage Serge7,Sheppard Richard8,Giannetti Nadia9,Lavoie Joël1,Mansour Asmaa10,Provost Sylvie12,Normand Valérie12,Mongrain Ian12,Langlois Mathieu12,O'Meara Eileen14,Ducharme Anique14,Racine Normand14,Guertin Marie-Claude10,Turgeon Jacques11,Phillips Michael S1,Rouleau Jean-Lucien14,Tardif Jean-Claude124,White Michel14,

Affiliation:

1. Research Center, Montreal Heart Institute, Montreal, Canada

2. Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Canada

3. Faculty of Pharmacy, Université de Montréal, Montreal, Canada

4. Faculty of Medicine, Université de Montréal, Montreal, Canada

5. McGill Health University, McGill University, Montreal, Canada

6. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada

7. Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada

8. Jewish General Hospital, McGill University, Montreal, Canada

9. Royal-Victoria Hospital, McGill University, Montreal, Canada

10. Montreal Health Innovations Coordinating Center, a division of the Montreal Heart Institute, Montreal Canada

11. CRCHUM, Research Center, Centre Hospitalier de l'Université de Montréal, Montreal, Canada

Abstract

Aim: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure. Materials & methods: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%. Results: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022). Conclusion: AGTR1 1166C carriers may experience a greater long-term compensatory renin–angiotensin–aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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