THE PARASAIL STUDY- CANADIAN REAL WORLD EXPERIENCE USE OF SACUBITRIL/VALSARTAN IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION

Abstract

PARASAIL was a Canadian prospective, multicenter, open-label study with the objective of characterizing over a 12 months period the real-life effectiveness, tolerability and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure with reduced ejection fraction (HFrEF). Participants were HFrEF outpatients with an ejection fraction of ≤ 40%, NYHA class II or III and on stable doses of ACEI or ARB and treated as per CCS guidelines and clinical judgment. The suggested starting dose of Sac/Val was 24/26 mg bid replacing ACEI or ARB, with an up-titration to 49/51 mg bid then to 97/103 mg bid every 2-4 weeks, however, the decision to up-titrate was left to the investigator’s discretion. Key exclusion criteria included symptomatic hypotension and/or SBP below 100 mmHg, estimated GFR below 30mL/min/1.73m2, angioedema or necessity to use ACEI or ARB concomitantly. Tolerability was assessed by; 1) assessing the number of patients remaining on the Sac/Val target dose of 97/103 mg bid at Month 6 (primary objective) and at Month 12; 2) measuring time to up-titration to the Sac/Val 49/51 mg dose and Sac/Val 97/103 mg dose; 3) measuring the number of dose reduction from Sac/Val 97/103 mg. Patients (n=302) had a mean age of 64 years, 80% male, 90% Caucasian, mostly NYHA Class II (83%), and 45% had prior heart failure-related hospitalization. The mean baseline ejection fraction was 29 ± 7.5% and blood pressure was 122/73 mmHg. Sac/Val starting dose of 24/26 mg was used for most patients (90%). At Month 6, 195 patients (64.6%) remained on the Sac/Val 97/103 mg dose, 46 patients (15.2%) remained on the 49/51 mg dose and 29 patients (9.6%) remained on the 24/26 mg dose. The majority of patients (65%) achieved the maximum dose of Sac/Val 97/103 mg at 12 weeks. At Month 12, 62% of the patients remained on the maximum dose of Sac/Val. Only a small proportion of patients (12%) have been down-titrated after achieving the maximal target dose of Sac/Val. Overall, the treatment was well tolerated with a discontinuation rate of 13% at Month 12. PARASAIL trial describes real-life tolerability and safety of Sac/Val in a Canadian HFrEF patient population. The results presented here showthat the target dose of Sac/Val 97/103 mg is generally achievable.