Background: Renin inhibition in heart failure with reduced ejection fraction (HF-REF)

1. JJV McMurray1, WT Abraham2, K Dickstein3, LV Køber4, MA Ali5, Y Chiang5, AS Desai6, C Gimpelewicz5, Q Sho5, SD Solomon6, G Tarnesby5, BM Massie7, H Krum8 on behalf of the ATMOSPHERE committees and investigators. 1University of Glasgow, UK; 2Ohio State University, USA; 3Stavanger University Hospital, Stavanger, Norway; 4Copenhagen University Hospital, Denmark; 6Brigham and Women's Hospital, Boston, USA; 5Novartis Pharma AG, Basel, Switzerland; 7University of California, San Francisco, USA; 8Monash University, Australia. Direct renin inhibition with aliskiren alone, and in combination with enalapril, compared with enalapril, in heart failure: Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE)

2. Background: Renin inhibition in heart failure with reduced ejection fraction (HF-REF) • ACE inhibitors reduce mortality and reduce heart failure hospitalization rates in patients with HF-REF, across the spectrum of symptom severity (CONSENSUS, SOLVD). • ARBs are an alternative in patients unable to tolerate an ACE inibitor because of cough (CHARM-Alternative). • ARBs futher reduce cardiovascular mortality (CHARM-Added) and heart failure hospitalization (CHARM-Added, Val-HeFT) when added to an ACE inhibitor. • Might a direct renin inhibitor (aliskiren) add to the benefit of an ACE inhibitor or be a better alternative to an ACE inhibitor?

3. Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) In reducing the risk of the primary composite outcome of cardiovascular death or heart failure hospitalization Superiority hypotheses • Aliskiren added to enalapril is superior to enalapril • Aliskiren monotherapy is superior to enalapril Non-inferiority hypothesis • Aliskiren monotherapy is non-inferior to enalapril https://clinicaltrials.gov NCT00853658

4. ATMOSPHERE: Entry criteria • Age ≥18 years. NYHA class II-IV. LVEF ≤0.35 • BNP ≥150 pg/ml (NTpro-BNP ≥600 pg/ml) or if HF hosp. within12 mo. BNP ≥100 pg/ml (NTpro-BNP ≥400 pg/ml) • Background ACEi therapy equivalent to enalapril ≥10 mg/d • Beta-blocker unless contraindicated/not tolerated • SBP ≥95 mmHg run-in/ ≥90 mmHg at randomization • eGFR ≥35 ml/min/1.73m2 at randomization /no decrease >25% during run in • Potassium <5.0 mmol/l run-in/ <5.2 mmol/l at randomization

5. ATMOSPHERE: Trial design Primary outcome: CV death or heart failure hospitalization (event driven: target 2318 patients [2369 accrued]) *89% 10mg bid †Target dose (titrated from 150mg qd) Randomization Enalapril 5-10mg bid* (n=2336) Enalapril 5-10mg bid Enalapril + Aliskiren150mg qd Aliskiren 300mg qd† (n=2340) Enalapril 5-10mg bid + Aliskiren300mg qd (n=2340) Open-label run-in Double-blind Median follow-up = 36.6 months 4-12 weeks Prior ACEi use discontinued

6. ATMOSPHERE: Baseline characteristics

7. ATMOSPHERE: Censoring of patients with diabetes* • Following the results of ALTITUDE (aliskiren added to an ACE-I/ARB in patients with diabetes and CKD/CVD) and ASTRONAUT (aliskiren added to an ACE-I/ARB in patients hospitalized with HF), the Clinical Trials Facilitation Group of the Heads of Medicines Agencies in Europe requested that patients with diabetes have study drug discontinued. • Follow-up for the efficacy analyses in patients with diabetes (and some others) who had treatment discontinued because of a regulatory request was censored at the date of implementation of these requests. Patients off study drug were still followed to end of the trial. • Median follow-up for analysis of efficacy in patients with diabetes was 24.1 months and in patients without diabetes was 46.0 months. *and some others

8. ATMOSPHERE: Trial conduct • Completeness of follow-up for vital status (at end of trial or regulatory censoring date). • Combination therapy: 31/2340 (1.3%) had unknown vital status. • Aliskiren: 19/2340 (0.8%) had unknown vital status. • Enalapril: 19/2336 (0.8%) had unknown vital status. • Study drug dose (mean ±SD) • Combination group:19.0 (3.0) mg of enalapril and 272 (58) mg of aliskiren; Aliskiren group: 276 (55) mg; Enalapril group 18.6 (3.5) mg. • Study drug discontinuation • Non-diabetics: Combination 44%, aliskiren 40%; enalapril 42%. Proportion of possible treatment time patients took study drug was 77%, 81% and 80%, respectively. • Diabetics: 31%, 28% and 32%; 80%, 84 and 82%, respectively.

9. Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) In reducing the risk of the primary composite outcome of cardiovascular death or heart failure hospitalization Superiority hypotheses • Aliskiren added to enalapril is superior to enalapril • Aliskiren monotherapy is superior to enalapril Non-inferiority hypothesis • Aliskiren monotherapy is non-inferior to enalapril https://clinicaltrials.gov NCT00853658

10. ATMOSPHERE: Primary outcome

11. ATMOSPHERE: Components of the primary composite outcome CV death HF hospitalization

12. ATMOSPHERE: Effect of combination therapy in patients with and without diabetes Effect of combination therapy on the primary outcome in patients without diabetes (*additional superiority hypothesis in revised statistical analysis plan) Interaction P-value = 0.35

13. Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) In reducing the risk of the primary composite outcome of cardiovascular death or heart failure hospitalization Superiority hypotheses • Aliskiren added to enalapril is superior to enalapril • Aliskiren monotherapy is superior to enalapril Non-inferiority hypothesis • Aliskiren monotherapy is non-inferior to enalapril https://clinicaltrials.gov NCT00853658

14. ATMOSPHERE: Comparison of enalapril and aliskiren monotherapy (non-inferiority) Pre-specified criterion for declaring non-inferiority was a P-value ≤0.0123 (one-sided) *Did not meet the pre-specified P-value for significance

15. ATMOSPHERE: Secondary and exploratory outcomes • Secondary outcome: • Kansas City Cardiomyopathy Questionnaire (KCCQ) - Change in the clinical summary score (CSS) from baseline to 12 months • Exploratory outcomes (selected): • Composite CV outcome: CV death, HF hospitalization, MI, stroke or resuscitated cardiac arrest • Composite renal outcome: renal death, ESRD (initiation of dialysis, renal transplantation, or a serum Cr above 6.0 mg/dl [530 μmol/l]), or doubling of serum Cr from baseline (to >upper limit of normal) sustained for at least 1 month

16. ATMOSPHERE: Pre-specified secondary outcome • = Comparison of enalapril plus aliskiren versus enalapril; (2)= Comparison of aliskiren versus enalapril

17. ATMOSPHERE: Pre-specified exploratory outcomes† • †Selected pre-specified outcomes • = Comparison of enalapril plus aliskiren versus enalapril; (2)= Comparison of aliskiren versus enalapril • * renal death, ESRD (initiation of dialysis, renal transplantation, or a serum Cr above 6.0 mg/dl [530 μmol/l]), or doubling of serum Cr from baseline (to >upper limit of normal) sustained for at least 1 month

18. ATMOSPHERE: All-cause mortality

19. Aliskiren n/N (%) Enalapril n/N (%) Combination n/N (%) Enalapril n/N (%) Interaction P-value Interaction P-value ATMOSPHERE: Pre-specified subgroups Favors enalapril Favors aliskiren Favors combination Favors enalapril

20. ATMOSPHERE: Safety outcomes • = Comparison of enalapril plus aliskiren versus enalapril; (2)= Comparison of aliskiren versus enalapril

21. Summary and conclusions Combination therapy • The addition of aliskiren to an evidence-based dose of enalapril led to more adverse events without an increase in benefit. • This finding differs from the prior ARB “add-on” trials and may reflect a difference in study design (the previous trials did not require an evidence-based dose of background ACE inhibitor). • There is probably a ceiling to RAS blockade in heart failure, above which there is no further benefit Aliskiren monotherapy • Non-inferiority was not demonstrated for aliskiren compared with enalapril.

22. In memory of our colleague and friend Henry Krum, 1958-2015 Henry Krum, 1958-2015

23. The following persons participated in the ATMOSPHERE trial Executive Committee: Original co-chairs Barry Massie and Henry Krum; co-chairs 2015- Henry Krum (Deceased 2015) and John McMurray; William Abraham, Kenneth Dickstein, Lars Køber. National Leaders: Argentina: Felipe Martinez; Australia: Peter McDonald; Austria: Martin Huelsmann, Richard Pacher (Deceased 2015); Belgium: Johan Vanhaecke; Brazil: Luiz Carlos Bodanese; Canada: Jonathan Howlett; China: Yuhua Liao; Colombia: Luis Eduardo Echeverria; Costa Rica: Mario Speranza; Czech Republic: Jiri Widimsky; Denmark: Lars Køber; Dominican Republic: Rafael Pichardo; Estonia: Riina Vettus; Finland: Ilkka Kantola; France: Yves Juilliere; Germany: Matthias Pauschinger, Stefan Anker; Greece: Ioannis Nanas; Ireland: Brendan McAdam Italy: Aldo Maggioni; Japan: Hiroyuki Tsutsui; Latvia: Janina Romanova; Lithuania: Ausra Kavoliuniene; Mexico: Jose Luis Arenas Leon; The Netherlands: Adriaan Voors; Norway: Marcel Moufack; Peru: Juan Lema; Poland: Piotr Ponikowski; Portugal: Cândida Fonseca; Russia: Yury Shvarts, Vyacheslav Mareev; Slovakia: Gabriel Kamensky; South Africa: Johan Roos; Korea: Byung-Hee Oh: Spain: López Sendón; Sweden: Jan Östergren; Switzerland: Frank Enseleit: Taiwan: Wenter Lai: Thailand: Piyamitr Sritara Turkey: Dilek Ural; UK: Iain Squire, Martin Cowie; USA: Eric Velazquez; Venezuela: María Inés Marulanda. Data Monitoring Committee:Karl Swedberg (Chair), Jeffrey S. Borer, Bertram Pitt, Stuart Pocock, Jean L. Rouleau. Clinical Endpoint Committee: Co-chairs: Scott D. Solomon and Akshay S. Desai; Director of Operations: Chau Duong; Business Administrator: Renee Mercier; Project Coordinator: Amanda Sullivan; Physician Reviewers: Natalie Bello, Ebrahim Barkoudah, Abdel Brahimi, Patricia Campbell, Davide Castagno, David Charytan, Miguel Morita Fernandes de Silva, Peter Finn, Aidan Flynn, Mauro Gori, L. Howard Hartley, Pardeep Jhund, Jacob Joseph, Rumen Kasabov, Wilson Nadruz Jr., Kayode Odutayo, Anne-Catherine Pouleur, Vinutha Rajesh, Odilson Silvestre, Olga Vasylyeva, Ali Vazir, Larry Weinrauch. Independent statistician: Nicola Greenlaw, Robertson Centre for Biostatistics, University of Glasgow. Countries (patients):Argentina (501), Australia (41), Austria (59), Belgium (73), Brazil (201), Canada (77), China (465), Colombia (146), Costa Rica (18), Czech Republic (307), Denmark (253), Dominican Republic (23), Estonia (47), Finland (24), France (34), Germany (470), Greece (59), India (782), Ireland (16), Italy (286), Japan (210), Republic of Korea (143), Latvia (65), Lithuania (61), Mexico (50), Netherlands (162), Norway (22), Peru (116), Poland (302), Portugal (54), Romania (290), Russia (553), Slovakia (327), South Africa (52), Spain (142), Sweden (141), Switzerland (15), Taiwan (113), Thailand (56), Turkey (70), United Kingdom (48), United States (116), Venezuela (76). Investigators: Argentina: Alvarenga Pablo, Moises Azize Guillermo, Baroni Marcos, Bendersky Mario, Luna Alejandra, Allende Guillermo, Colombo Hugo, Cuneo Carlos, Montenegro Eleonora, Diez Fabian, Garcia Pinn Jorge, Prado Aldo, Ibañez Luz, Aiub Jorge, Jure Horacio, Resk Jorge, Luquez Hugo, Majul Claudio, Marin Marcos, Martinez Jimena, Montana Oscar, Muntaner Juan, Perna Eduardo, Piskorz Daniel, Poy Carlos, Ronderos Ricardo, Scaro Graciela, Sosa Liprandi Maria, Acosta Adriana, Vigo Santiago, Zangroniz Pedro, García Brasca Daniela, Fernandez Alberto, Dominguez Andrea, Caccavo Alberto, Garcia Duran Ruben, Budassi Nadia, Sosa Carlos. Australia: J Karrasch, T Marwick, B Singh, E Vogl, I Jeffrey, C DePasquale, P MacDonald, M Fitzpatrick, D Cross, K Kostner. Austria: Hülsmann Martin, Jakl Gabriele, Hoppe Uta, Fruhwald Friedrich, Frick Matthias, Siostrzonek Peter, Breier Roland, Kunschitz Evelyn, Ebner Christian. Belgium: Vanhaecke Johan, Hollanders Geert, Nellessen Eric, Mullens Wilfried, Thoeng John, Missault Luc, Troisfontaines Pierre, Marenne Frédéric, Lozano Angel, Delforge Marc, Roelandt Raf, Gurne Olivier, Vlassak Irmien. Brazil: Bodanese Luiz, Rocha Augusto, Leaes Paulo, Precoma Dalton, Finimundi Helius, Pelloso Eraldo, David Joao, Saraiva Jose, Bittencourt Marcelo, Moura Lidia Ana, Canesin Manoel, Clausell Nadine, Marino Roberto Luis, Rassi Salvador, Alves Silvia, Barbosa Eduardo, Abib Eduardo, Saad Jamil, Vieira Nubia, Sampaio Roney, Saporito Wladmir. Canada: Gupta Milan, Howlett Jonathan, Mouzayek Kouz Simon, Pandey Shekhar, Searles Greg, Bergeron Sebastien, White Michel, Constance Christian, Haddad Haissam, Talbot Paul. China: J Ge, M Wei, G Lu, S Wu, N Sun, Y Ke, W ZHU, S Lv, H Li, L Zhang, Y Chen, W Ding, W Gao, T Hu, Z Li, J Hu, X Li, H Li, Y Hao, X Li, L Tang, G Fu, N Wang, J Wang, T Jiang, H Chen, Y Dong, D Xu, Y Liao, W Jin, Z Yao, J Chen, X Ji, Y Zheng, R Zhao.Colombia: María Elías, Echeverria Luis, Cotes Carlos, Botero Rodrigo, Manzur Fernando, Urina Miguel, Torres Adriana, Jaramillo Mónica, Roa Nubia, Moncada Miguel, Jaramillo Carlos, Ternera Ernesto, Reynales Humbert. Costa Rica: Arce Mario, Speranza Mario, Valerio Fernando, Camacho Sergio. Czech Republic: Skalicka Hana, Jerabek Ondrej, Kuchar Roman, Maratka Tomas, Berka Lubomir, Kuchar Jiri, Kobza Richard, Smid Jan, Krais Ladislav, Machova Vilma, Homza Miroslav, Dedkova Svatava, Nechvatal Libor, Matyasek Ivo, Belohlavek Jan, Naplava Robert, Tyl Petr, Busak Ladislav, Kochrt Milan. Denmark: J Larsen, N Ralfkjaer, S Rasmussen, P Joergensen, N Bruun, I Raymond, K Klarlund, J Schou, N Nielsen, G Gislason, L Koeber, J Nielsen, J Handberg, O Nielsen, J Petersen, S Hvitfeldt, E Nielsen, A Vittrup, E Korup, K Egstrup, H Andersen, J Markenvard, H Rickers, L Videbaek.Dominican Republic: Almonte Claudio, Diaz Pedro, Pichardo Rafael, Velazco Casimiro, Martinez Petronila. Estonia: R Vettus, V Vahula, M Reimand, J Eha. Finland: I Kantola, J Rinne, T Keski-Opas, K Nyman, H Kervinen. France:Juilliere Yves, Habib Gilbert, Garbarz Eric, Isnard Richard, Cohen Ariel, Douard Herve, Eicher Jean-Christophe, Frances Yves-Michel, Salvat Muriel, Remaud Philippe, Regimbart Christine, Rumeau Philippe. Germany: Duengen Hans-Dirk, Pauschinger Matthias, Abdel Qader Muwafeg, Abel Christoph, Ammer Konrad, Aring Ralf, Auch-Schwelk Wolfgang, Preissner Andreas, Barth Andreas, Beermann Jens, Schmitt Susanne, Brachmann Johannes, Brandstetter Ralf, Brode Marcus, Nuding Sebastian, Claus Gunther, Deissner Michael, Dengler Thomas, Faghih Markus, Voigt Jan-Gerrit, Geschke Evelyn, Hofmann Monika, Graemer Gernot, Grooterhorst Peter, Gutting Matthias, Wachter Rolf, Hoenen Stefan, Horacek Thomas, Jaensch Sybille, Jordan Ralf, Frankenstein Lutz, Klingenheben Thomas, Konermann Martin, Kruck Irmtraut, Landers Bernhard, Marks Hans-Joachim, Meffert Christian, Meisel Eckhard, Mitrovic Veselin, Mueller Otmar, Nagel Frank, Omran Heyder, Reinig Karsten, Richard Frank, Sarnighausen Hans-Eckart, Scheibner Thomas, Schellong Sebastian, Schneider Diethold, Schulze Matthias, Schweizer Johannes, Stellmach Heiko, Stelzner Frank, Sulliga Martin, Unkelbach Manfred, Voehringer Hans-Friedrich, Vormann Reinhold, Weier Bernd, Werner Gerald, Winkelmann Bernhard, Wolde Claus-Henning, Schulze Uwe, Marschner Juergen, Schwerin Gerhard, Holmer Stephan, Kraemer Alfred, Bott Jochen, Darius Harald, Osterhues Hans-H, Rieker Werner, de Haan Fokko, Baar Markus, Hanefeld Christoph, Sanuri Mazin, Weimer Joachim, Barakat Alain, Henke Roswitha, Moericke Ruediger, Bodammer Michael, Schoen Norbert, Baeumer Anselm, Erlinger Rudolf, Merke Juergen, Taggeselle Jens, Hensen Johannes, Wichterich Klaus, Hansen Claudius, Gaub Regina, Killat Holger, Troeger Steffen, Foerster Andreas, Lankisch Mark, Hohensee Hartmut, Krummenerl Annette, Becker Bernd, Stratmann Matthias, Landgraf Irmgard, Stoerk Stefan, Melchior Klaus, Natour Mohammed, Regner Stefan, Menzel Frank, Schiffer Clemens, Knapp Markus. Greece: J Nanas, F Gerasimos, T Konstantinos, V Pyrgakis, C Karvounis, P Makridis, I Zarifis, N Smyrnioudis. India: A Ravikanth, D Talwar, S Selvamani, A Mohanty, P Kumar, M Thomas, P Reddy, S Mandyam, J Gupta, B Pinto, N Khanna, S Kareem, T Nair, A Khan, M Lohkare, J Arneja, V Bisne, S Suryawanshi, P Grant, V Pai, N Patki, K Jothiraj, T Alexanader, O Naidu, K Sharma, A Joshi, A Kapoor, V Narain, V Sharma, V Srinath, V Kale, K Mohan, A Awasthi, D Chauhan, R Saligrama, S Sahu, R Polavarapu, A Mahajan, S Washimkar. Italy: Glorioso Nicola, Bernardinangeli Marino, Aucello Giuseppe, Volpe Massimo, Di Somma Salvatore, Mos Lucio, Fascetti Ferdinando, Sinagra Gianfranco, Di Biase Matteo, Bertoli Daniele, Frisinghelli Anna, Scalvini Simonetta, Febo Oreste, Brunazzi Maria Cristiana, De Pellegrin Annamaria, Murrone Adriano, Bosi Stefano, Marra Sebastiano, Calò Leonardo, Saba Pier Sergio, Minneci Calogero, Oltrona Visconti Luigi, Pagnoni Nicoletta, Lembo Giuseppe, Baroni Monica, Bolognese Leonardo, Caserta Carlo, Venturini Elio, De Santis Fernando, Margonato Alberto, De Caterina Raffaele, Piovaccari Giancarlo, Pedretti Roberto, Agostoni Pier Giuseppe, Anselmi Maurizio, Opasich Cristina, Bernardi Daniele, Bianconcini Michele, Ferrini Donatella, Metra Marco, Baldassi Mara, Cosmi Franco, Partesana Nora, Fucili Alessandro, Borghi Claudio, Romei Manuela, Di Lenarda Andrea, Montagna Laura, Perna Gian Piero, Senni Michele. Japan: T Takenaka, S Taguchi, S Sakagami, A Hanatani, K Fujii, R Tamura, M Sata, H Urata, T Muroya, T Yamamoto, T Murohara, T Yamanouchi, M Yasutake, T Fujii, T Wakeyama, Y Hiasa, T Inomata, I Tei, T Sakai, T Ogawa, S Joho, Y Kihara, M Hatano, Y Nagai, S Nanba, Y Sato, S Kinugawa, M Isobe, H Takano, H Tsuboi, K Aonuma, Y Seino, M Yamamuro, K Node, K Saku, H Daida, H Kawata, M Ajioka, H Iida, K Kimura, K Sugimura, N Hagiwara, A Yamada, S Suzuki, T Kawasaki, T Iwasawa. Korea: B Oh, S Chae, Y Kim, D Choi, E Jeon, J Ha, H Seo, Y Ahn, J Kim, J Bae, M Shin, K Ryu. Latvia: J Romanova, N Rozkova, I Veze, A Gersamija. Lithuania: A Kavoliuniene, L Jankauskiene, A Rudys, D Jarasuniene. Mexico: Leon Salvador, Bayram Edmundo, Cardona Ernesto, Velasco Raul, Gonzalez Guerra Jose, Arenas Jose, Garcia Elias, De los Rios Manuel. Netherland: A Voors, A.Breeman, R Troquay, J Herrman, J Tanka, L Cozijnsen, P Keulen, T Lenderink, R Breedveld, P Nierop, M Freericks, J. Cornel, M Keijzers, P Hoogslag, J Lok, Y Pinto, M Pieterse, H Mevissen, D Heijden, J Heymeriks, N Windy. Norway: D Atar, M Moufack, J Otterstad. Peru: Alegre Raul, Coloma Ricardo, Parra Jose, Medina Felix, Reyes Miguel, Villanueva Francisco, Segura Luis, Yanac Pedro, Rios Carlomagno, Lema Juan, Sanabria Enrique, Camacho Luis, Gomez Sanchez Jorge. Poland: Ponikowski Piotr, Tarchalski Janusz, Sciborski Ryszard, Krzciuk Malgorzata, Kalarus Zbigniew, Loboz-Grudzien Krystyna, Nowalany-Kozielska Ewa, Kusnierz Barbara, Derlaga Boguslaw, Szpajer Michal, Krynicki Romulad, Kudzelka Jolanta, Dluzniewski Miroslaw, Swierczynska-Pusz Urszula, Kolodziejczyk Jacek, Baska Jan, Staneta Pawel, Negrusz-Kawecka Marta, Napora Piotr, Nadbrzezny Piotr, Wilczewski Przemyslaw, Golba Krzysztof, Ciemniewski Zbigniew, Berkowski Piotr, Miekus Pawel, Ogorek Michal, Bednarski Janusz, Jaworska Krystyna, Szyszka Andrzej, Zielinski Tomasz, Jankowski Piotr. Portugal: C Fonseca, C Aguiar, M Fiuza, N Lousada, P Monteiro, P Bettencourt, A Andrade, P Gago, J Alves, J Bastos. Romania: Stanciulescu Gabriela, Blajan Daniel, Spiridon Marilena, Virgil Sandru, Pal Istvan Kikeli, Zdrenghea Dumitru, Vida-Simiti Luminita, Pop Calin Florin, Calomfirescu Nicoleta, Podoleanu Cristian, Alexandru Tom Mihai, Popescu Mircea, Radoi Mariana, Ionac Adina, Tudoran Mariana, Ott Dragos, Stoenescu Radu, Crisu Daniela,Russia: V Zadionchenko, L Pavlova, T Morozova, S Martsevich, V Lusov, E Akatova, B Sidorenko, A Kuchmin, N Gratsiansky, S Yakushin, A Rebrov, Y Shvarts, P Dovgalevskiy, O Khrustalev, A Khokhlov, Y Lopatin, S Nedogoda, V Skibitskiy, R Valeeva, N Maximov, K Zrazhevsky, S Shustov, M Sitnikova, V Simanenkov, O Berkovich, N Perepech, S Shulenin, E Maryasova, . Y Nikitin, O Khromtsova, N Izmozherova, A Kuzin, E Volkova, I Shaposhnik, N Koziolova, L Gapon, V Kuznetsov, Y Karpov, V Moiseev, I Nikolskaya, N Shilkina, Y Shapovalova, A Duda, O Solovev, A Kuzmenko, V Dvornikov, D Dronov, L Strongin, V Rezvan. Slovakia: Dukat Andrej, Benacka Jozef, Litvinova Jana, Bugan Viliam, Vinanska Daniela, Dzupina Andrej, Kohlerova Edita, Kamensky Gabriel, Uhliar Rudolf, Hranai Marian, Nociar Jan, Radomska Maria, Farsky Stefan, Toth Peter, Bodnar Juraj, Horvat Peter, Snincak Marian, Lasanova Zuzana, Jakubova Ingrid, Kolikova Veronika, Spisak Vladimir, Gonsorcik Jozef, Juhas Stanislav, Sojka Gabriel, Spurny Peter. South Africa: E Klug, J Roos, I Ebrahim, M Essop, M Alison, I Mitha, C Dyk. Spain: Garcia Puig Juan, Delgado Jimenez Juan, Bover Freire Jose Ramon, Gomez Bueno Manuel, Galve Basilio Enrique, Castel Lavilla Mª Angeles, Noguero Blum Mariana, Lupon Roses Josep, Bardaji Alfredo, Ridocci Soriano Francisco, De Teresa Parreno Luis, Diaz Molina Beatriz, Castro Almudena, Formiga Perez Francesc, Calvo Gomez Carlos, Beltran Robles Manuel, Sanchez Aquino Rosa, Sanz Avertillo Nieves, Fernandez Romero Antonio Jose, Castro Antonio, Garcia del Rio Enrique, Martinez-Selles D´Oliveira Soa Manuel, Sweden: J Ostergren, C Lindholm, R Zlatewa, K Lindmark, K Boman, S Berglund, F Al-Khalili, K Jansson, Z Trivic, M Lycksell, E Andersson, M Fu, L Klintberg, S Cizinsky, G Vikstroem, M Schaufelberger, U Lofstrom, S Bandh, P Cherfan, K Tolagen, G Tasevska. Switzerland: F Enseleit, P Rickenbacher, T Moccetti, S Zbinden, T Burkard, C Roethlisberger, A Gallino, M Romanens. Taiwan: C Lee, C Hou, M Wen, K Chang, L Tsai, S Chen, W Lai, Z Chen. Thailand: P Sritara, B Sunsaneewitayakul, A Sukonthasarn, R Krittayaphong, N Sansanayudh. Turkey: D Ural, O Badak, Y Guray, Z Yigit, S Aydogdu, D Dursunoglu, T Tekten, C Barcin, M Akin, M Yilmaz, L Koldas.USA: Weiss Robert, Lowes Brian, Krueger Steven, Wright Richard, Scott Cranford, Vijay Nampalli, Kuiper Johannes, VanHammersveld Daniel, Frais Michael, Dauber Ira, Litt Marc, Wainwright William, Loh Irving, Mody Freny, Hoagland Peter, Kapoor Divya, Kozinn Marc, Saba Souheil, Collins Gary, Richards Mary, Saadat Mohsen, Gress Jeffery, Vossler Mark, Karunaratne Harischandra, Wu Lambert, Ewald Gregory, Gelernt Mark, Skopicki Hal, Shah Ronak, Bozkurt Biykem,Deichmann Richard, Anderson H. Vernon, Wise Jonathan, Banchs Pieretti Hector, Van Bakel Adrian, Shealy Neal, Smith Mark, Burnham Kenneth, Chomsky Donald, Di Salvo Thomas, Haught Herbert, Massey Clara, McGrew Frank, Schocken Douglas, Lepor Norman, Johnson David, Pla Alejandro, Davis Paul, Weber Bruce, Kraus David, Vazquez-Tanus Jose, Rios De Alonso Maria, Chow Christopher, Kreher Susan, Chaleff Frederick, Foucauld Jean, Henderson David, Hargrove Joe, Brown Christopher, Iteld Bruce, McKenzie Wilfred, Akinboboye Olakunle, Weinstein Debra, Rama Bhola. Venezuela: Isea Jesus, Antepara Norka, Guevara Lempira, Gonzalez Alicex, Beer Nusen, Diaz Luis, Maitas Leonardo, Geraldino Oscar, Marulanda Maria, Mendoza Ivan. Sponsor, Novartis Established Medicines Development Franchise: (Current)Paul Aftring, David Aitken, M. Atif Ali, Lutz Hegemann, Georgia Tarnesby. Previous (Development Franchise): Juergen Armbrecht, Claudio Gimpelewicz, Deborah Keefe,Anastasia Lesogor, Maria Nicolaides, Bernard Reimund. Global Clinical Operations: Current: Stephanie Barou, Ashwini Belsare, Ilse Devrieze, Vishal Mishra, Julien Roustan, Asit Shete, Abhishek Sople, Cathy Surdouski. Previous: Nicolas Carlo, Sreekanth Kunchetty, Arshad Nehaljamali, AmitPadadharia, Ursula Potts. Local Clinical Operations: Gabriela Arantes (Argentina); Kathryn Stephens (Australia); Yvonne Tomberger, Sarah Keusch (Austria); Bart Ryckaert, Caroline Guinee (Belgium); Oliveira Carolina (Brazil); Pascale Raymond, Caroline Garneau (Canada); Wu Ying (China); Andrea Romero (Colombia); Carolina Schoua (Costa Rica, Dominican Republic); Stepanka Vejsadova, Martina Hajkova, Martin Vrlik (Czech Republic); Sissel Nustad (Denmark, Finland, Norway, Sweden); Natalija Robacevskiene (Estonia, Latvia, Lithuania); Sabine Sauger, Thierry Gormon (France); Frauke Krepulat, Jane Stilmann, Jennifer Etschel (Germany); Vaia Koutra (Greece); Akshatha Shetty (India); Rajinder Nerwan (Ireland, United Kingdom); Ilic Orsini (Italy); Hideki Maruyama (Japan); Hyezue Lee (Korea); Jorge Rojas (Mexico); Nine van Zadelhoff  (Netherland); Alexandra Lopez (Peru); Magdalena Michalewicz (Poland); Sara Esteves (Portugal)Silviu Morariu, Selena Boghiu (Romania); Alexander Lents (Russia); Alexandra Lelkesova, Robert Vavra (Slovakia); Lindie Traut (South Africa); Enrique Fernandez Taboada (Spain); Oliver Meub (Switzerland); Jenny Huang (Taiwan); Supunnee Kittisiriprasert (Thailand); Nurhat Bayraktar (Turkey); Linda Ivankoe (USA); Odalys Sosa (Venezuela). Integrated Information Systems: Current: Yanntong Chiang, Nathalie Ezzet, Hui Fang, Santhosh Lyathakula, Sarmistha Roy,Qing Shao. Previous: Albert Kandra. Drug Supply Management: Tamara Spuergin. ATMOSPHERE43 countries, 844 Sites, 7064 Patients Thank You