Ulrik M Mogensen1, Lars Køber2, Søren L Kristensen2, Pardeep S Jhund3, Jianjian Gong4, Martin P Lefkowitz4, Adel R Rizkala4, Jean L Rouleau5, Victor C Shi4, Karl Swedberg6, Michael R Zile7, Scott D Solomon8, Milton Packer9, John J V McMurray10. 1. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK; Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. 2. Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. 3. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 4. Novartis Pharmaceutical Corporation, East Hanover, NJ. 5. Institut de Cardiologie de Montréal, Montréal, Canada. 6. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; National Heart and Lung Institute, Imperial College, London, United Kingdom. 7. Medical University of South Carolina and RHJ Department of Veterans Administration Medical Center, Charleston, SC. 8. Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA. 9. Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX. 10. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. Electronic address: john.mcmurray@glasgow.ac.uk.
Abstract
BACKGROUND:Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. CONCLUSIONS: Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited.
RCT Entities:
BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. CONCLUSIONS: Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited.
Authors: Vyacheslav A Korshunov; Breandan Quinn; Abrar Faiyaz; Rifat Ahmed; Mark P Sowden; Marvin M Doyley; Bradford C Berk Journal: Br J Pharmacol Date: 2019-06-24 Impact factor: 8.739
Authors: Rafał Niemiec; Irmina Morawska; Maria Stec; Wiktoria Kuczmik; Andrzej S Swinarew; Arkadiusz Stanula; Katarzyna Mizia-Stec Journal: Int J Environ Res Public Health Date: 2022-02-13 Impact factor: 3.390
Authors: Leanne Mooney; Nathaniel M Hawkins; Pardeep S Jhund; Margaret M Redfield; Muthiah Vaduganathan; Akshay S Desai; Jean L Rouleau; Masatoshi Minamisawa; Amil M Shah; Martin P Lefkowitz; Michael R Zile; Dirk J Van Veldhuisen; Marc A Pfeffer; Inder S Anand; Aldo P Maggioni; Michele Senni; Brian L Claggett; Scott D Solomon; John J V McMurray Journal: J Am Heart Assoc Date: 2021-11-19 Impact factor: 6.106