Akshay S Desai1, Muthiah Vaduganathan1, John G Cleland2,3, Brian L Claggett1, Ebrahim Barkoudah1, Peter Finn1, Finnian R McCausland4, Mehmet B Yilmaz5, Martin Lefkowitz6, Victor Shi6, Marc A Pfeffer1, John J V McMurray7, Scott D Solomon1. 1. Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women's Hospital, Boston, MA. 2. Robertson Centre for Biostatistics, Institute of Health and Wellbeing and British Heart Foundation Centre of Research Excellence, University of Glasgow, United Kingdom (J.G.C.). 3. National Heart and Lung Institute, Imperial College, London, United Kingdom (J.G.C.). 4. Renal Division (F.R.M.), Brigham and Women's Hospital, Boston, MA. 5. Department of Cardiology, Dokuz Eylul University, Izmir, Turkey (M.B.Y.). 6. Novartis Pharmaceuticals, East Hanover, NJ (M.L., V.S.). 7. British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.).
Abstract
BACKGROUND: Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction. METHODS: PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms. RESULTS: Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P<0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30). CONCLUSIONS: Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
BACKGROUND: Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction. METHODS: PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms. RESULTS: Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P<0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30). CONCLUSIONS: Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
Authors: Akshay S Desai; Pardeep S Jhund; Brian L Claggett; Muthiah Vaduganathan; Zi Michael Miao; Toru Kondo; Ebrahim Barkoudah; Abdel Brahimi; Eugene Connolly; Peter Finn; Ninian N Lang; Finnian R Mc Causland; Martina McGrath; Mark C Petrie; John J V McMurray; Scott D Solomon Journal: JAMA Cardiol Date: 2022-10-03 Impact factor: 30.154
Authors: Maoning Lin; Jiachen Zhan; Yi Luan; Duanbin Li; Yu Shan; Tian Xu; Guosheng Fu; Wenbin Zhang; Min Wang Journal: Front Cardiovasc Med Date: 2022-05-11