The PARASAIL study- Patient Reported Outcomes from the Canadian Real World Experience use of Sacubitril/Valsartan in Patients with Heart Failure and Reduced Ejection Fraction

Background PARASAIL is the first Canadian prospective, multicenter, open-label study which aims at characterizing the real-life effectiveness and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure with reduced ejection fraction (HFrEF) treated for a 12 months period. Here we present the final analysis results of the PARASAIL Study for the tolerability and effect of sacubitril/valsartan (Sac/Val) on quality of life (QoL). Methods Participants were HFrEF outpatients with an ejection fraction of ≤ 40%, NYHA class II or III and on stable doses of ACEI or ARB with additional HF treatment as per CCS guidelines. The suggested starting dose of Sac/Val was 24 mg/26 mg bid replacing ACEI or ARB, with an up-titration to 49 mg/51 mg bid then to 97 mg/103 mg bid every 2-4 weeks or as per clinical judgement. Symptomatic hypotension and/or SBP below 100 mmHg, estimated GFR below 30mL/min/1.73m 2 , angioedema or necessity to use ACEI or ARB concomitantly, were amongst the exclusion criteria. Changes in quality of life was measured with the patients Minnesota living with HF questionnaire (MLHFQ), EQ-5D questionnaire and patient global assessment (PGA) at baseline and at 4, 12 and 24 weeks after conversion to Sac/Val. Results Patients (n=302) had a mean age of 64 years, 80% male, 90% Caucasian, mostly NYHA Class II (83%), with a mean baseline ejection fraction of 29 ± 7.5% and blood pressure of 122/73 mmHg. Sac/Val starting dose of 24/26 mg was used for most patients (90%) and up-titration to maximum dose of Sac/Val was achieved for the majority (65%) at 12 weeks. Quality of life significantly improved: 52% of patients reported a significant improvement of their overall scores at week 4, 59% at week 12 and 64% at week 24 as measured with PGA. Using MLHFQ, patients experienced a 19%, 21% and 23% decrease in the score compared to baseline at weeks 4 and 24 with respectively (all p Conclusion The PARASAIL trial was designed to evaluate the real-life therapeutic effectiveness, tolerability and safety of Sac/Val in HFrEF patients. Although the lack of a comparator group limits the interpretation, the results shown by the validated questionnaires indicate a potential early and sustained improvement in Quality of Life at week 4, week 12 and week 24 of treatment with Sac/Val compared to baseline, in line with results from PARADIGM.