Canadian Real-World Experience of Using Sacubitril/Valsartan in Patients With Heart Failure With Reduced Ejection Fraction: Insight From the PARASAIL Study

Abstract

Background To determine the effectiveness of sacubitril/valsartan 97/103 mg twice daily (b.i.d.) on tolerability, safety, and quality of life (QoL) in Canadian patients with heart failure with reduced ejection fraction in a real-life setting. Methods In P rospective, Multicenter, Open L a bel, Post-App r ov a l S tudy Ai med at Characterizing the Use of L CZ696 at 97 mg Sacubitril/103 mg Valsartan bid in Patients With HFrEF (PARASAIL), an open-label, prospective, phase IV, multicentre study, outpatients with heart failure with reduced ejection fraction and New York Heart Association functional class II-III were followed up for 12 months. The suggested starting dose of sacubitril/valsartan was 24/26 mg b.i.d. replacing angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, with an uptitration to 97/103 mg b.i.d. or as per clinical judgement. The primary endpoint was the proportion of patients achieving the target dose of sacubitril/valsartan 97/103 mg b.i.d. after 6 months of treatment. Results For the 302 patients included, the mean age was 64.47 years, and a majority of patients (82.8%) belonged to New York Heart Association class II. Overall, 195 (64.6%) patients were on maximum dose of sacubitril/valsartan 97/103 mg b.i.d. after 6 months and 62.3% remained on this dose at month 12. Using patient global assessment, patients experienced an improvement in QoL. For Minnesota Living with Heart Failure Questionnaire scores, a significant decrease from the baseline was observed at weeks 4, 12, and 24 ( P < 0.0001 for all), which indicated an improvement in QoL. The patient global assessment and Minnesota Living with Heart Failure Questionnaire results correlate with moderate but significant changes in Euro quality of life-5D visual analogue scale scores. Conclusions Results of the PARASAIL study in a real-life setting have shown that most patients were on sacubitril/valsartan 97/103 mg b.i.d. and the treatment was well tolerated. The patient-reported outcomes showed an overall improvement in patients’ QoL.

Sacubitril‐valsartan initiation in chronic heart failure patients impacts sleep apnea: the ENTRESTO‐SAS study

“…This appears similar to the 35.7% of patients reported at 7 months in a non-selected cohort, 32 but low compared with a further report mentioning >60% of the patients with a 97/103 mg SV dosage at 6 months. 31 We also report that 12.65% of our patients presented an SV-associated hypotension, which is similar to the fraction (10.3%) reported in the PARASAIL study. 31 Only 3.80% of our whole population presented a 30% decrease in eGFR in comparison, which is quite comparable with the 3.03% reported by Pharithi et al 35 Limits and strengths of the study A limit, but also a strength, of our study is the real-life design.…”

“…31 We also report that 12.65% of our patients presented an SV-associated hypotension, which is similar to the fraction (10.3%) reported in the PARASAIL study. 31 Only 3.80% of our whole population presented a 30% decrease in eGFR in comparison, which is quite comparable with the 3.03% reported by Pharithi et al 35 Limits and strengths of the study A limit, but also a strength, of our study is the real-life design. Although randomized controlled trials are the gold standard for evaluating treatment effects, they may not always fully represent what happens in real life because of inherent selection bias.…”

“…), and 64.41% with mineralocorticoid receptor antagonist, as in previous reports. [29][30][31][32][33] After SV initiation, NT-proBNP values decreased by 30% or more in 51.72% of the whole population (a threshold considered as clinically significant 22,34 ), which is near the 46.3% reported by Pharithi et al 35 In G1 patients, SV initiation was associated with an improvement in right ventricular function as previously reported. 29,33 SV also improved the NYHA class, the Minnesota Living with Heart Failure Questionnaire scores, and the EQ-5D VAS scores, as previously reported.…”

Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study

“…The QoL improvement with sac/val treatment is an important issue and, according with this, in PARADIGM-HF it occurred early after 8 months as demonstrated by increase in KCCQ (McMurray JJ, et al, 2014) and this finding has been also reported in different real life settings so as Parasail study and Provide-HF (Haddad H, et al, 2020;Mentz RJ, et al, 2020) after a follow-up of 12 weeks and 12 months, respectively. Our study shows more consistent data because the QoL improvement rises up at 6 months by the start of the treatment with sac/val and it persists over 24 months.…”

“…The potential reverse remodelling effect of sac/val has been demonstrated in the PRIME study, a prospective randomized trial showing that sac/val is more effective than the only angiotensin receptor blocker to improve functional mitral regurgitation HF associated after 12 months of follow-up, without significant changes in LVEF (Kang DH, et al, 2019). Moreover, several real world evidence studies have reported an improvement of cardiac remodelling markers and patients' functional capacity (Spannella F, et al, 2019;Moliner-Abós C, et al, 2019;Wachter R, et al, 2019;Haddad H, et al, 2020;Mentz RJ, et al, 2020;Correale M, et al, 2020;Cosentino et al, 2019;Martens P, et al, 2018). In particular, a retrospective cohort study on a small number of HFrEF patients showed, after a mean follow-up of 14 months, a significant improvement in LVEF and GLS (De Vecchis R, et al, 2019).…”