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Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: Insights from the TITRATION study
Senni, Michele McMurray, John Wachter, Rolf McIntyre, Hugh F. Anand, Inder S. Duino, Vincenzo Sarkar, Arnab Shi, Victor C. Charney, Alan
Senni, Michele
McMurray, John
Wachter, Rolf
McIntyre, Hugh F.
Anand, Inder S.
Duino, Vincenzo
Sarkar, Arnab
Shi, Victor C.
Charney, Alan
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: 100–110 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.
Keywords
LCZ696, Sacubitril/valsartan, Heart failure, Tolerability, Hypotension, Blood pressure, Titration
Date
2018
Type
Journal article
Journal
European Journal of Heart Failure
Book
Volume
20
Issue
3
Page Range
491-500
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
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Controlled