| dc.description.abstract | AimsTo assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction 35%). Methods and resultsA 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (condensed' regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (conservative' regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naive patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (condensed' vs. conservative') 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for condensed' vs. conservative'; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/condensed' vs. high-dose/conservative' and 84.9% vs. 73.6% (P = 0.030) for low-dose/conservative' vs. low-dose/condensed'. ConclusionsInitiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group. | en_US |
| dc.contributor.department | [Senni, Michele] Azienda Osped Papa Giovanni XXIII, Heart Failure & Heart Transplant Unit, Cardiol, Piazza OMS, I-24127 Bergamo, Italy -- [McMurray, John J. V.] Univ Glasgow, British Heart Fdn Cardiovasc Res Ctr, Glasgow, Lanark, Scotland -- [Wachter, Rolf] Univ Med Goettingen, Clin Cardiol & Pneumol, Gottingen, Germany -- [McIntyre, Hugh F.] Brighton & Sussex Med Sch, Med, Brighton, E Sussex, England -- [Reyes, Antonio] Univ Hosp Virgen de Valme, Med Interna, Seville, Spain -- [Andreka, Peter] Gottsegen Gyorgy, Orszagos Kardiol Int, Felnott Kardiol Osztaly, Budapest, Hungary -- [Shehova-Yankova, Nina] MHAT Bratan Shukerov, Dept Cardiol, Smoljan, Bulgaria -- [Anand, Inder] Vet Med Ctr Minneapolis, Minneapolis, MN USA -- [Yilmaz, Mehmet B.] Cumhuriyet Univ, Fac Med, Cardiol, Sivas, Turkey -- [Gogia, Harinder] Cardiol Consultants Orange Cty, Anaheim, CA USA -- [Martinez-Selles, Manuel] Hosp Gregorio Maranon, Serv Cardiol, Madrid, Spain -- [Martinez-Selles, Manuel] Univ Europea, Madrid, Spain -- [Martinez-Selles, Manuel] Univ Complutense, Madrid, Spain -- [Zilahi, Zsolt] Kardiol Szakrendeles, Nyiregyhaza, Hungary -- [Cosmi, Franco] UO Cardiol, PO Osped Valdichiana S Margherita, Cortona, Italy -- [Gelev, Valeri] MHAT Tokuda Hosp Sofia, Clin Cardiol & Angio, Sofia, Bulgaria -- [Galve, Enrique] Hosp Valle De Hebron, Cardiol, Barcelona, Spain -- [Gomez-Doblas, Juanjo J.] Hosp Virgen de la Victoria, Cardiol, Campus Univ Teatinos, Malaga, Spain -- [Nociar, Jan] Kardio 1 Sro, Lucenec, Slovakia -- [Radomska, Maria] Letesia Sro, Trebisov, Slovakia -- [Sokolova, Beata] Galenum Sro, Ambulancia & Odbore Vutorne Lekarstvo, Bratislava, Slovakia -- [Volterrani, Maurizio] IRCCS San Raffaele Pisana, Rome, Italy -- [Sarkar, Arnab] Novartis HC Ltd, Hyderabad, Andhra Pradesh, India -- [Reimund, Bernard] Novartis Pharma AG, Basel, Switzerland -- [Chen, Fabian -- Charney, Alan] Novartis Pharmaceut, E Hanover, NJ USA | en_US |
