Michele Senni1, John J V McMurray2, Rolf Wachter3, Hugh F McIntyre4, Inder S Anand5, Vincenzo Duino1, Arnab Sarkar6, Victor Shi7, Alan Charney7. 1. Cardiology Division, Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy. 2. British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 3. Clinic for Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany. 4. Cardiology Department, Conquest Hospital, St Leonards on Sea, UK. 5. Veterans Medical Center Minneapolis, Minneapolis, MN, USA. 6. Novartis Healthcare Ltd, Hyderabad, India. 7. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Abstract
AIMS: The TITRATION trial investigated two strategies to initiate and up-titrate sacubitril/valsartan (LCZ696) to the same target dose, over a condensed (3-week) or conservative (6-week) period, in patients with heart failure with reduced ejection fraction (HFrEF) and systolic blood pressure (SBP) of ≥100 mmHg. This post hoc analysis examined the relationship between baseline SBP at screening and achievement of the target dose of sacubitril/valsartan of 97 mg/103 mg (also termed 'LCZ696 200 mg') twice per day during the study. METHODS AND RESULTS: Patients (n = 498) were categorized in four groups based on SBP at screening: 100-110mmHg (n = 70); 111-120 mmHg (n = 93); 121-139 mmHg (n = 168) and ≥140mmHg (n = 167). Overall, 72.7%, 76.1%, 85.6% and 82.9%, respectively, of patients in these SBP categories achieved and maintained the target dose of sacubitril/valsartan without down-titration/dose interruption over 12 weeks ('treatment success'). Compared with patients with SBP of 100-110mmHg, rates of treatment success among patients in the higher SBP groups [111-120 mmHg (P = 0.96); 121-139 mmHg (P = 0.06) and ≥140 mmHg (P = 0.25)] did not differ significantly. A higher percentage of patients with lower SBP (100-110 mmHg) achieved treatment success with gradual up-titration (6 weeks) (∼80%) than with rapid up-titration (∼69%). Similar findings were observed with regard to 'tolerability success' (maintenance of the target dose for at least the final 2 weeks prior to study completion). Hypotension occurred more frequently in patients with lower SBP. CONCLUSIONS: The majority of patients (>80%) with SBP of ≥100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually. These findings suggest that low SBP should not prevent clinicians from considering the initiation of sacubitril/valsartan.
RCT Entities:
AIMS: The TITRATION trial investigated two strategies to initiate and up-titrate sacubitril/valsartan (LCZ696) to the same target dose, over a condensed (3-week) or conservative (6-week) period, in patients with heart failure with reduced ejection fraction (HFrEF) and systolic blood pressure (SBP) of ≥100 mmHg. This post hoc analysis examined the relationship between baseline SBP at screening and achievement of the target dose of sacubitril/valsartan of 97 mg/103 mg (also termed 'LCZ696 200 mg') twice per day during the study. METHODS AND RESULTS:Patients (n = 498) were categorized in four groups based on SBP at screening: 100-110 mmHg (n = 70); 111-120 mmHg (n = 93); 121-139 mmHg (n = 168) and ≥140 mmHg (n = 167). Overall, 72.7%, 76.1%, 85.6% and 82.9%, respectively, of patients in these SBP categories achieved and maintained the target dose of sacubitril/valsartan without down-titration/dose interruption over 12 weeks ('treatment success'). Compared with patients with SBP of 100-110 mmHg, rates of treatment success among patients in the higher SBP groups [111-120 mmHg (P = 0.96); 121-139 mmHg (P = 0.06) and ≥140 mmHg (P = 0.25)] did not differ significantly. A higher percentage of patients with lower SBP (100-110 mmHg) achieved treatment success with gradual up-titration (6 weeks) (∼80%) than with rapid up-titration (∼69%). Similar findings were observed with regard to 'tolerability success' (maintenance of the target dose for at least the final 2 weeks prior to study completion). Hypotension occurred more frequently in patients with lower SBP. CONCLUSIONS: The majority of patients (>80%) with SBP of ≥100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually. These findings suggest that low SBP should not prevent clinicians from considering the initiation of sacubitril/valsartan.
Authors: Jennifer Cautela; Jean-Michel Tartiere; Alain Cohen-Solal; Anne Bellemain-Appaix; Alexis Theron; Thierry Tibi; James L Januzzi; François Roubille; Nicolas Girerd Journal: Eur J Heart Fail Date: 2020-04-30 Impact factor: 15.534
Authors: Rebabonye B Pharithi; Maria Ferre-Vallverdu; Alan S Maisel; Eoin O'Connell; Myra Walshe; Claire Sweeney; James Barton; Kathrine McDonald; Daniel O'Hare; Chris Watson; Joe Gallagher; Mark Ledwidge; Kenneth McDonald Journal: ESC Heart Fail Date: 2020-01-05