Disclosure Statement This study was sponsored by Novartis Pharma AG, - PowerPoint PPT Presentation

1 Disclosure Statement • This study was sponsored by Novartis Pharma AG, Basel, Switzerland • Executive Committee and other investigators or their institutions received a consultancy fee • Some authors are employees of Novartis and therefore eligible for stock and stock options Clinicaltrials.gov: NCT00549757 ESC 2012 - Munich

2 The Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) Hans-Henrik Parving 1,2 , Barry M Brenner 3 , John JV McMurray 4 , Dick de Zeeuw 5 , Steven M Haffner 6 , Scott D Solomon 7 , Nish Chaturvedi 8 , Frederik Persson 9 , A. S. Desai 7 , Maria Nicolaides 10 , Alexia Richard 10 , Zhihua Xiang 10 , Juergen Armbrecht 10 and Marc A Pfeffer 7 (on behalf of the ALTITUDE investigators) 1 Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Denmark; 2 Faculty of Health Science, Aarhus University, Denmark; 3 Renal Division, Brigham and Women’s Hospital, and Harvard Medical School, Boston, USA; 4 BHF Cardiovascular Research Centre, University of Glasgow, UK; 5 Department of Clinical Pharmacology, University Medical Centre Groningen, University of Groningen, The Netherlands; 6 Department of Medicine and Clinical Epidemiology, San Antonio, USA; 7 Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, USA; 8 Imperial College, London, UK; 9 Steno Diabetes Center, Gentofte, Denmark; 10 Novartis Pharma AG, Basel, Switzerland

3 Kaplan-Meier estimate for time to the primary composite end-point 30 Aliskiren (nEvent = 767) 28 Placebo (nEvent = 721) 26 HR = 1.08, 95%CI = (0.98, 1.20), p = 0.14 24 Cumulative Event Rate (%) 22 20 18 16 14 12 10 8 6 4 2 0 Month = 0 6 12 18 24 30 36 42 48 Aliskiren (nRisk) = 4274 4077 3890 3603 2847 2139 1250 598 68 Placebo (nRisk) = 4287 4104 3888 3630 2938 2210 1283 588 65 Time (months) and patients at risk

4 ALTITUDE Hazard ratios for the individual components of the primary endpoint Patients with events, n (%) Aliskiren Placebo Hazard ratio P- N = 4274 N = 4287 (95 % CI) value Composite Endpoint 767 (17.9) 721 (16.8) 1.08 (0.98, 1.20) 0.142 CV death 239 (5.6) 213 (5.0) 1.13 (0.94, 1.36) 0.184 Resuscitated sudden death 18 (0.4) 8 (0.2) 2.28 (0.99, 5.23) 0.053 Myocardial infarction 142 (3.3) 140 (3.3) 1.02 (0.81, 1.29) 0.858 Stroke 146 (3.4) 118 (2.8) 1.25 (0.98, 1.60) 0.070 Unplanned hospitalization for heart failure 202 (4.7) 219 (5.1) 0.93 (0.77, 1.13) 0.462 Doubling of baseline serum creatinine 205 (4.8) 215 (5.0) 0.96 (0.79, 1.16) 0.650 Onset of ESRD or renal death 118 (2.8) 108 (2.5) 1.10 (0.85, 1.43) 0.465 Death 375 (8.8) 355 (8.3) 1.07 (0.92, 1.23) 0.388 Endpoints shown represent 92% of projected value of 1620 events for the primary composite endpoint Adjusted for UACR and CVD history Events adjudicated with cut-off date 31 Jan 2012

5 ALTITUDE AEs/SAEs – Potassium Lab analysis Aliskiren (N = 4272) 25 Aliskiren n (%) 38.7 Placebo Placebo (N = 4285) 20 892 (21.0) 15 683 % (16.0) 28.6 10 373 (8.8) 5 239 % (5.6) 0 ≥5.5 -6.0 ≥6.0 K + mmol/L mmol/L 12.1 9.6 8.0 7.2 2.8 2.6 SAE SAE SAE SAE SAE SAE 1.1 0.5 0.7 0.8 0.3 0.4 0.5 0.2 Hyperkalemia Hypotension Diarrhoea Falls