Abstract 19378: First Experience with Concomitant AT1 and Neprilysin (NEP 24.11) Inhibition with LCZ696 in Patients with Chronic Heart Failure
Introduction: In the setting of heart failure (HF), chronic RAAS activation is detrimental, while NEP (neprilysin, NEP 24.11) activation is expected to induce a beneficial response. LCZ696, an angiotensin receptor neprilysin inhibitor (ARNI), offers the synergy of concomitant angiotensin II AT1 receptor and neprilysin enzyme inhibition. We report the first results of LCZ696 in patients with stable chronic HF, exploring the tolerability of LCZ696.
Methods: Patients with stable HF (NYHA II-IV, LVEF <40), on optimal medical therapy entered an open-label study. After a short washout of ACEI therapy, patients were treated with LCZ696 100 mg BID for 7 days and then uptitrated to 200 mg BID for an additional 14 days, maintaining other chronic stable background therapy. Patients remained in the clinic during the study period.
Results: Thirty patients (NYHA II 56%, LVEF 33.6±4.6%, male 83.3%, BMI 30.7±4.6kg/m2) entered the study. Background treatment included θ-blockers (90%), ASA (90%), statin (50%), aldosterone antagonists (33.3%), Ca-antagonists (16.7%), nitrates (33.3%), loop diuretics (63.3%), thiazide diuretics (26.7%) and digoxin (13.3%). Twenty-seven subjects completed the study, with no discontinuations due to hypotension; three subjects were withdrawn due to serum K+ values >5.5 mEq/L. Seven other patients had transient potassium increases that were normal at the final treatment visit. No serious adverse events (AEs) were reported. Overall 21 (70%) subjects experienced one or more AEs (53.3% on LCZ696 100 mg and 50% on 200 mg BID). Most common clinical AEs were dizziness (13.3%), headache (10%) and insomnia (6.7%). Two cases of syncope were reported, one hypoglycemic and one vasovagal, and there was one case of worsening HF; none of these were felt to be drug related. Plasma NT-pro BNP decreased from 1050.0±1162.3 to 664.7±765.9 (p<0.01 vs baseline) during the study.
Summary: Patients in chronic cardiac failure were safely switched from ACEI treatment to LCZ696. No serious AEs and no cases of angioedema were reported during the study. LCZ696 was well tolerated in patients with chronic stable HF.
- © 2010 by American Heart Association, Inc.