Abstract
BACKGROUND: Experience with sacubitril-valsartan in real-world patients with heart failure and reduced ejection fraction (HFrEF) is congruent with findings from clinical trials. Detailed assessment of safety and clinical outcomes in the Canadian context is less well explored. METHODS: The PAtient RegisTry assessing effectiveness and safety of HEart failure treatment with LCZ696 acrOss CaNada (PARTHENON) was a prospective, observational, multicentre study. Patients with HFrEF who were prescribed sacubitril-valsartan were recruited from 32 sites across Canada and followed for at least 3 years. The primary outcome was the association between baseline natriuretic peptide levels and the combined endpoint of all-cause mortality or all-cause hospitalization. Secondary outcomes included incidence of hypotension, hyperkalemia, and renal impairment. Additionally, observed all-cause mortality was compared with risk-model predicted mortality. RESULTS: A total of 996 patients were enrolled in the registry; 19.1% discontinued the study early, and 10.8% died. No statistically significant association occurred between baseline natriuretic peptide levels and all-cause mortality or all-cause hospitalization (adjusted hazard ratio 1.04; 95% confidence interval: 0.91-1.20). Clinically relevant hypotension, hyperkalemia, and an increased creatinine level were observed in 24%, 4%, and 24%, respectively. The mean absolute change in left ventricular ejection fraction over 18 months was +8.2% +/- 10.8%. The observed 3-year mortality rate was lower than the 3-year mortality rate predicted by the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (10.8%, vs 29% +/- 13.7%); observed survival was higher than the Seattle Heart Failure Model predicted survival (89.2%, vs 53.4% +/- 26.4%). CONCLUSIONS: The PARTHENON registry confirms the safety and tolerability of sacubitril-valsartan in patients with HFrEF in a real-world setting. The registry also demonstrated improvement in left ventricular ejection fraction, and a lower mortality rate, compared to the predicted mortality rate in this population.