Author + information
- Received April 24, 2020
- Accepted May 11, 2020
- Published online September 28, 2020.
- Domingo Pascual-Figal, MD, PhDa,b,∗ (, )@domingopascualf,
- Rolf Wachter, MDc,d,e,
- Michele Senni, MDf,
- Weibin Bao, MSg,
- Adele Noè, PhDh,
- Heike Schwende, PhDi,
- Dmytro Butylin, MDi,
- Margaret F. Prescott, PhDg,
- on behalf of the TRANSITION Investigators
- aCardiology Department, Virgen de la Arrixaca University Hospital, Universidad de Murcia, Murcia, Spain
- bCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- cClinic and Policlinic for Cardiology, University Hospital Leipzig, Leipzig, Germany
- dClinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany
- eGerman Cardiovascular Research Center, partner site Göttingen, Göttingen, Germany
- fCardiology Division, Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
- gNovartis Pharmaceuticals, East Hanover, New Jersey
- hNovartis Pharma AG, Basel, Switzerland
- ↵∗Address for correspondence:
Dr. Domingo Pascual-Figal, Cardiology Department, Virgen de la Arrixaca University Hospital, Universidad de Murcia, Murcia, Spain.
Objectives This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response.
Background NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF).
Methods Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline.
Results In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p < 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose ≥49/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor–naive or angiotensin receptor blocker–naive, and no prior myocardial infarction.
Conclusions In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)
- acute decompensated heart failure
- heart failure with reduced ejection fraction
- N-terminal pro–B-type natriuretic peptide
- TRANSITION study
This study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Pascual-Figal has served on the advisory board for and/or received speaker honoraria from Novartis, Servier, Roche, AstraZeneca, Vifor, Pfizer, and Abbott. Dr. Wachter has served on the advisory board for and/or received speaker honoraria from Boehringer Ingelheim, Bayer, CVRx, Medtronic, Novartis, Pfizer, Sanofi, and Servier; and received research grant supports from Boehringer Ingelheim, the European Union, and Bundesministerium für Bildung und Forschung. Dr. Senni has received consultancy fees and/or speaker honoraria from Novartis, Bayer, Abbott, Merck, AstraZeneca, Vifor Pharma, and Boehringer Ingelheim. Drs. Bao, Noè, Schwende, Butylin, and Prescott are employees of Novartis.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received April 24, 2020.
- Accepted May 11, 2020.
- 2020 The Authors