John R Teerlink1, Beth A Davison2, Gad Cotter2, Aldo P Maggioni3, Naoki Sato4, Ovidiu Chioncel5, Georg Ertl6, G Michael Felker7, Gerasimos Filippatos8, Barry H Greenberg9, Peter S Pang10, Piotr Ponikowski11, Christopher Edwards2, Stefanie Senger2, Sam L Teichman12, Olav Wendelboe Nielsen13, Adriaan A Voors14, Marco Metra15. 1. Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, CA, USA. 2. Momentum Research, Inc., Durham, NC, USA. 3. Italian Association of Hospital Cardiologists (ANMCO) Research Center, Florence, Italy. 4. Cardiology and Intensive Care Unit, Nippon Medical School, Musashi-Kosugi Hospital, Kawasaki, Japan. 5. University of Medicine Carol Davila, Bucharest, Romania. 6. Julius-Maximilians-Universität Würzburg, Würzburg, Germany. 7. Division of Cardiology, Duke University School of Medicine, Durham, NC, USA. 8. Athens University Hospital Attikon, Athens, Greece. 9. Division of Cardiology, University of California, San Diego, CA, USA. 10. Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. 11. Department of Heart Diseases, Medical University, Military Hospital, Wroclaw, Poland. 12. Formerly Corthera, San Carlos, CA, USA. 13. Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. 14. University Medical Center Groningen, Groningen, The Netherlands. 15. Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
Abstract
AIMS: The effectiveness and safety of 48 h intravenous 30 μg/kg/day serelaxin infusion in acute heart failure (AHF) has been studied in six randomized, controlled clinical trials. METHODS AND RESULTS: We conducted a fixed-effect meta-analysis including all studies of intravenous serelaxin initiated within the first 16 h of admission for AHF. Endpoints considered were the primary and secondary endpoints examined in the serelaxin phase III studies. In six randomized controlled trials, 6105 total patients were randomized to receive intravenous serelaxin 30 μg/kg/day and 5254 patients to control. Worsening heart failure to day 5 occurred in 6.0% and 8.1% of patients randomized to serelaxin and control, respectively (hazard ratio 0.77, 95% confidence interval 0.67-0.89; P = 0.0002). Serelaxin had no statistically significant effect on length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration resulted in statistically significant improvement in markers of renal function and reductions in both N-terminal pro-B-type natriuretic peptide and troponin. No significant adverse outcomes were noted with serelaxin. Through the last follow-up, which occurred at an average of 4.5 months (1-6 months), serelaxin administration was associated with a reduction in all-cause mortality, with an estimated hazard ratio of 0.87 (95% confidence interval 0.77-0.98; P = 0.0261). CONCLUSIONS: Administration of intravenous serelaxin to patients admitted for AHF was associated with a highly significant reduction in the risk of 5-day worsening heart failure and in changes in renal function markers, but not length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration was safe and associated with a significant reduction in all-cause mortality.
RCT Entities:
AIMS: The effectiveness and safety of 48 h intravenous 30 μg/kg/day serelaxin infusion in acute heart failure (AHF) has been studied in six randomized, controlled clinical trials. METHODS AND RESULTS: We conducted a fixed-effect meta-analysis including all studies of intravenous serelaxin initiated within the first 16 h of admission for AHF. Endpoints considered were the primary and secondary endpoints examined in the serelaxin phase III studies. In six randomized controlled trials, 6105 total patients were randomized to receive intravenous serelaxin 30 μg/kg/day and 5254 patients to control. Worsening heart failure to day 5 occurred in 6.0% and 8.1% of patients randomized to serelaxin and control, respectively (hazard ratio 0.77, 95% confidence interval 0.67-0.89; P = 0.0002). Serelaxin had no statistically significant effect on length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration resulted in statistically significant improvement in markers of renal function and reductions in both N-terminal pro-B-type natriuretic peptide and troponin. No significant adverse outcomes were noted with serelaxin. Through the last follow-up, which occurred at an average of 4.5 months (1-6 months), serelaxin administration was associated with a reduction in all-cause mortality, with an estimated hazard ratio of 0.87 (95% confidence interval 0.77-0.98; P = 0.0261). CONCLUSIONS: Administration of intravenous serelaxin to patients admitted for AHF was associated with a highly significant reduction in the risk of 5-day worsening heart failure and in changes in renal function markers, but not length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration was safe and associated with a significant reduction in all-cause mortality.
Authors: Abdelrahman N Emara; Noha O Mansour; Mohamed Hassan Elnaem; Moheb Wadie; Inderpal Singh Dehele; Mohamed E E Shams Journal: J Clin Med Date: 2022-05-31 Impact factor: 4.964
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