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Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Extrapolating Long-term Event-Free and Overall Survival With Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis of a Phase 3 Randomized Clinical Trial
JAMA Cardiology  (IF14.676),  Pub Date : 2021-11-01, DOI: 10.1001/jamacardio.2021.2632
Kieran F. Docherty, Pardeep S. Jhund, Brian Claggett, João Pedro Ferreira, Olof Bengtsson, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Anna Maria Langkilde, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Mikaela Sjöstrand, Scott D. Solomon, John J. V. McMurray, DAPA-HF Investigators and Committees, John J.V. McMurray , David L. DeMets , Silvio E Inzucchi , Lars Køber, Mikhail N. Kosiborod, Anna Maria Langkilde, Felipe A. Martinez , Piotr Ponikowski, Marc S. Sabatine, Mikaela Sjöstrand, Scott D. Solomon, Mirta Diez, Jose Carlos Nicolau, Tzvetana Katova, Jonathan Howlett, Eileen O’Meara, Subodh Verma, Junbo Ge, Jan Belohlavek, Morten Schou, Michael Böhm, Bela Merkely, Vijay Chopra, Masahumi Kitakaze, Rudolf De Boer, Jarosław Drożdż, Sergey Tereshchenko, Andrej Dukát, Charlotta Ljungman, Chern-En Chiang, Mark Petrie, Inder Anand, Akshay Desai, Pham Nguyễn Vinh, S Sassone, D Aizenberg, M Talavera, G Mercau, D Martinez, J Albisu, A Hershson, R García Durán, M Hominal, N Cluigt, F Colombo Berra, E Perna, R Ahuad Guerrero, D García Brasca, C Zaidman, C Majul, J Taborda, H Luquez, J Sala, A Sosa Liprandi, G Cursack, O Montaña, A Fernandez, M Najenson, S Nani, G Caruso, E Fairman, S Pereiro Gonzalez, L Maia, A Pereira, P Rossi, D Precoma, F Neuenschwander, G Reis, F Guimaraes, J Saraiva, F Arantes , M Hernandes, J Borges, B Paolino, E Vasconcellos, E Manenti, P Pimentel, P Leaes, S Rassi, T Dalcoquio, T Katova, D Avramov, N Spasova, D Raev, B Chompalova, M Milanova, M Tokmakova, N Runev, A Mihov, A Gogov, A Dincheva , N Iliev, B Kolomanov, Y Ivanova, K Ilieva, D Karageorgiev, I Efremov, N Botushanov, S Vladeva, C Constance, S Vizel, A Pandey, D Phaneuf, S Mehta, D Rupka, Y Pesant, P Poirier, R Chehayeb, M Babapulle, E O’Meara, J Howlett, L Yao, R Mckelvie, S Verma, M Hartleib, R Vijayaraghavan, J Vyselaar, F Azzari, J Cha, F Nasser-Sharif, T.Z. Maung, S Mansour, Y Khaykin, R Lee, P Fong, H Jiang, X Li, L Fu, Y Li, D Wang, Q Zhao, Y Dong, Y Zhou, X Lin, J Dong, X Zhang, Z Zheng, W Huang, Y Gu, J Liu, X Guo, L Wu, Q Tang, D Peng, W Dong, Y Liang, Z Li, Z Wang, B Han, C Wu, J Belohlavek, J Slaby, J Spinar, P Hajek, L Busak, J Carda, L Spinarova, I Malek, J Skopek, R Kuchar, E Krcova, O Mayer Jr, D Kucera, M Schou, L Køber, K Egstrup, J Hove, G Gislason, L Videbæk, M Böhm, R Nischik, N Toursarkissian, K Appel, E Schmidt, I Weigmann, M Kellerer, A Al-Zoebi, U Stephan, A Wilke, S Genth-Zotz, G Simonis, D Tschöpe, A Costard-Jäckle, B Merkely, P Andrássy, E Noori, Z Járai, F Poór, C Király, A Czigány, L Nagy, Á Motyovszki, G Masszi, V Mehta, V Chopra, A Naik, M Gadkari, R Sawant, M Mahapekar, S Karna, M Deshpande, V Bhargava, V Kothiwale, J Menon, D Sinha, S Sinha, H Kokane, P Udgire, M Sandhu, M Suzuki, M Nishino, A Kiyosue, K Sumii, S Suzuki, Y Noguchi, S Tanaka, H Takase, M Mohri, S Higashiue, N Fujimoto, H Iseki, T Kuramochi, T Shibasaki, H Tsutsui, Y Takagi, Y Katayama, N Takeyasu, T Anzai, H Nagashima, A Kimura, T Kakuta, T Hashimoto, H Sugino, K Saito, S Hiroi, H Kamiya, K Fukui, S Matsuoka, K Moritani, Y Tomobuchi, Y Hata, R Kawamura, E Hattori, K Fujimoto, N Takahashi, W Takahashi, T Kadokami, H Ueno, S Uchikawa, T Shinozaki, Y Onishi, N Komiyama, S Inoue, Y Momiyama, Y Ueda, Y Komura, T Arakawa, H Meno, M Higuchi, Y Hayashi, K Seki, K Fujii, K Harada, A Wada, T Kasai, K Kuwahara, Y Yasaka, I Uchida, Y Okumura, Y Hisamatsu, T Nunohiro, K Tsukahara, A Hirohata, M Asakura, R De Boer, L Bellersen, H Swart, B Groenemeijer, S Zoet Nugteren, C De Nooijer, P Nierop, R Robles De Medina, J Van Eck, M Van Hessen, J Drożdż, P Miękus, R Ściborski, B Mikłaszewicz, W Sudnik, R Mariankowski, R Witek, G Drelich, E MirekBryniarska, S Szynal, L Pawłowicz, J Lampart, R Korzeniak, J Prokopczuk, S Boldueva, Y Didenko, N Dzhaiani, L Ermoshkina, V Kostenko, E Vishneva, N Koziolova, S Tereschenko, D Pevzner, L Krylova, A Chernyavsky, A Kazakov, S Aksentiev, R Nilk, Z Paltsman, A Galyavich, A Maltcev, P Kopylov, A Ezhov, J Shilko, L Antalik, V Bugan, P Fulop, L Jamriskova, D Kollarova, V Macek, M Slovenska, L Tomasova, D Vinanska, R Smik, J Selecky, I Majercak, P Olexa, C Ljungman, A Hedman, C Lindholm, K Lindmark, T Mooe, C Chiang, L Lin, M Liu, K Chang, C Hsia, J Shih, P Liu, T Lin, H Chang, J Huang, I Hsieh, W Tseng, M Petrie, R Gardner, A Clark, A Japp, P Jhund, C Lang, S Leslie, C Murphy , C Petrie, J Walsh, A Arif , D Avino, S Banerjee, M Kanwar, M Berk, C Brown, C Ince Jr, T Lewis, A Nikfarjam, J Patel, K Ramanathan, A Schabauer, T Greene, K Shah, R Sotolongo, A Viera, O Akinboboye, A Arouni, B Bertolet, L Chandra, T Cimato, S Deleon, M Bennett, F Franchi, G Hamroff, D Hotchkiss, M Jardula, J Javier, N Kazemi, J Kostis, J Lash, L Levinson, I Lieber, E Lo, S Mahal, R Manshadi, F Mody, A Paraschos, M Pursley, G Hickey, J Londono, D Singal, S Srivastava, J Teel, J Castriz, L Kantaros, C Venugopal, C Staniloae, D Gupta, F Syed, M Zacharias, N Jaffrani, P Wakefield, M Nassif, T Haddad, S Iskander, G Lewis, B Al-Joundi, W French, M Ogunniyi, S Emani, S Weiss, R Cheng, V Florea, S Joseph, S Lederman, J Izzo, M Bernstein, E Fruehling, B Foley, L Younis, D Song, V Pham, H Nguyen, H Do, B Truong, T Nguyen, D Ho

Importance Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients.

Objective To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime.

Design, Setting, and Participants Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months.

Interventions Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy.

Main Outcomes and Measures The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause.

Results A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival.

Conclusions and Relevance These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF.

Trial Registration ClinicalTrials.gov Identifier: NCT03036124