Tolerability and efficacy of sacubitril/valsartan in clinical practice

Abstract

Background Heart failure (HF) is a major cause of morbidity and mortality. Sacubitril/valsartan has demonstrated reductions in HF hospitalisation, and all‐cause mortality in patients with heart failure with reduced ejection fraction. Aims To assess the tolerability and efficacy of sacubitril/valsartan in an intention to treat patient cohort. Methods Sixty‐five patients who were commenced on sacubitril/valsartan in 2017 at a major metropolitan centre in Victoria were retrospectively audited. Clinical outcomes and quality of life scores were obtained pre and post sacubitril/valsartan commencement through phone and regular clinic follow up, 6–12 months after commencement of sacubitril/valsartan. Results Fourteen percent of patients were able to achieve maximal dose (97/103 mg twice daily) whilst 37% remained on 49/51 mg and 23% on 24/26 mg. The mean systolic blood pressure reduced from 118 ± 18 mmHg to 109 ± 15 mmHg with symptomatic hypotension (30%) being the most common side‐effect leading to dose reduction or drug cessation. Left ventricular ejection fraction improved from 29.1 ± 9.7% to 33.8 ± 9.9% (P < 0.05) on drug. There was also a significant improvement in quality of life scores; EQ5D‐VAS 40 pre versus 67 post sacubitril/valsartan (P < 0.05), and New York Heart Association class (P < 0.05). Importantly, 10 patients lost an existing indication for device based therapy after treatment with sacubitril/valsartan. Conclusions Sacubitril/valsartan is a much needed therapeutic advancement in the treatment of HF. Our study indicates it is well tolerated with improvements in cardiac function and symptoms. Sacubitril/valsartan could redefine the definition of ‘optimal medical therapy’ when assessing patients for device based therapies.

Predictors of sacubitril/valsartan high dose tolerability in a real world population with HFrEF

“…Baseline SBP is, of course, the primary determinant for achieving of higher Sac/Val dose. In our cohort, a significant reduction in BP was observed during follow‐up, and hypotension still represents, in several observational studies, the main determinant of ineffective up‐titration 24 . Elderly patients are frailer, with a higher co‐morbidity burden and, therefore, more prone to adverse effects during up‐titration, compared with the selected trial population 7 .…”

“…In our cohort, a significant reduction in BP was observed during follow‐up, and hypotension still represents, in several observational studies, the main determinant of ineffective up‐titration. 24 Elderly patients are frailer, with a higher co‐morbidity burden and, therefore, more prone to adverse effects during up‐titration, compared with the selected trial population. 7 Finally, as expected, the baseline tolerability of ACEi/ARBs maximum dose plays a key role in achieving of Sac/Val target dose, in line with previous literature findings.…”

Effect of angiotensin receptor neprilysin inhibitor on physical activity in patients with heart failure with reduced ejection fraction, monitored by implantable electronic device home monitoring

“…Current guidelines recommend up-titration of ARNI to the highest dose tolerated by the patient, with a minimal effective daily dose of 48/52 mg 1,14,33 . Due to the blood-pressure-lowering effect of ARNI, maximal doses are frequently not well tolerated by patients 33–35 . In a recent study evaluating the tolerability of an ARNI up-titration, only 14% of patients tolerated the maximal daily dose of 194/206 mg, whereas nearly a quarter of the patients in this study remained on the minimal daily dose of 48/52 mg 33 .…”

“…As reported by Kraai et al , 32 more than half of patients with symptomatic heart failure prefer to improve their quality of life, even at the expense of longevity. Current guidelines recommend up-titration of ARNI to the highest dose tolerated by the patient, with a minimal effective daily dose of 48/52 mg 1,14,33 . Due to the blood-pressure-lowering effect of ARNI, maximal doses are frequently not well tolerated by patients 33–35 .…”

The Efficacy and Safety of Sacubitril/Valsartan in Heart Failure Patients: A Review

“…A retrospective cohort study reported significant improvements in NYHA class ( P < 0.05) and the quality of life scores on the EQ5D-VAS (standardized instrument to measure health outcomes) ( P < 0.05) in HFrEF patients treated with sacubitril/valsartan after 6 to 12 months of follow-up. 50 In another retrospective cohort study, sacubitril/valsartan therapy obviously improved NYHA class from 2.3 ± 0.6 to 1.8 ± 0.5 ( P < 0.001), increased LVEF from 31.2 ± 7.0% to 37.3 ± 10.5% ( P < 0.001) and decreased the level of NT-pro-BNP from 3884 ± 4871 pg/ml to 1975.3 ± 3006.6 pg/ml ( P = 0.0001) in HFrEF patients after 316.1 ± 155.9-day follow-up. 51 However, given the weak level of evidence from observational studies, RCTs and meta-analyses should be implemented.…”