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

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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

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The Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

Hans-Henrik Parving1,2, Barry M Brenner3, John JV McMurray4, Dick de Zeeuw5, Steven M Haffner6, Scott D Solomon7, Nish Chaturvedi8, Frederik Persson9, A. S. Desai7, Maria Nicolaides10, Alexia Richard10, Zhihua Xiang10, Juergen Armbrecht10 and Marc A Pfeffer7 (on behalf of the ALTITUDE investigators)

1Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Denmark; 2Faculty of Health Science,

Aarhus University, Denmark; 3 Renal Division, Brigham and Women’s Hospital, and Harvard Medical School, Boston, USA;

4BHF Cardiovascular Research Centre, University of Glasgow, UK; 5 Department of Clinical Pharmacology, University Medical

Centre Groningen, University of Groningen, The Netherlands; 6Department of Medicine and Clinical Epidemiology, San Antonio, USA; 7 Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, USA; 8Imperial College, London, UK; 9Steno Diabetes Center, Gentofte, Denmark; 10Novartis Pharma AG, Basel, Switzerland

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Kaplan-Meier estimate for time to the primary composite end-point

Aliskiren (nEvent = 767) Placebo (nEvent = 721) HR = 1.08, 95%CI = (0.98, 1.20), p = 0.14

Cumulative Event Rate (%) Time (months) and patients at risk

Aliskiren (nRisk) = 4274 4077 3890 3603 2847 2139 1250 598 68 Placebo (nRisk) = 4287 4104 3888 3630 2938 2210 1283 588 65

Month = 0 6 12 18 24 30 36 42 48

30 28 26 24 22 20 18 16 14 12 10 8 6 4 2

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ALTITUDE Hazard ratios for the individual components of the primary endpoint

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

Patients with events, n (%) Aliskiren N = 4274 Placebo N = 4287 Hazard ratio (95 % CI) P- 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

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Hyperkalemia Hypotension Diarrhoea Falls

5 10 15 20 25

ALTITUDE AEs/SAEs – Potassium Lab analysis

≥5.5-6.0 mmol/L ≥6.0 mmol/L

n (%)

892 (21.0) 373 (8.8) 683 (16.0) 239 (5.6)

K+ %

%

38.7 28.6 12.1 8.0 9.6 7.2 2.8 2.6 SAE 1.1 SAE 0.5 SAE 0.7 SAE 0.8 SAE 0.3 SAE 0.4 0.5 0.2

Aliskiren (N = 4272) Placebo (N = 4285)

Aliskiren Placebo