1. P H Y S I C I A N S ’ A C A D E M Y F O R C A R D I O V A S C U L A R E D U C A T I O N Insights from clinical trials: The unassailable case for LDL-c lowering Kausik Ray, MD St Georges University London, United Kingdom Master class: Exploring the clinical innovations in lipid management? June 4-5, 2010, Barcelona

2. P H Y S I C I A N S ’ A C A D E M Y F O R C A R D I O V A S C U L A R E D U C A T I O N Prof. Kausik Ray: Biography Dr Ray is per June 2010 Professor of Cardiovascular Disease Prevention at St George’s University of London on the Monday. Dr. Kausik Ray received his BSc (Hons) in Pharmacology and MBChB from Birmingham Medical School, and subsequently completed his post graduate training in the West Midlands obtaining his MRCP (UK). He undertook higher specialist training in Cardiology in the West Midlands and Sheffield. He received his MD from the University of Sheffield, studying the role of the IL-1 locus in coronary disease and endothelial function, as a British Heart Foundation Junior Research Fellow, under Professor David Crossman. After completing his clinical training at Sheffield, he was a British Heart Foundation International Fellow at Harvard Medical School/Brigham and Women’s Hospital, working in the TIMI study group under Dr Eugene Braunwald and Dr Christopher Cannon. Whilst in US he undertook many of the key analyses of high dose statin therapy for the management of acute coronary syndromes (ACS) and studies of novel biomarkers in patients with ACS. His clinical interests are in preventative cardiology and the pathogenesis and management of acute coronary syndromes. His present research in Cambridge (funded by the British Heart Foundation) focuses on large scale studies of cardiometabolic risk factors, and in particular adipokines and HDL in prospective studies. He is also assessing the practical utility of novel biomarkers in the management of patients with coronary artery disease.

3. Clinical Events Correlate Directly With On-Treatment LDL-Cholesterol Levels P = placebo; S = statin. Reproduced from O'Keefe et al. J Am Coll Cardiol. 2004;43:2142, with permission. CHD Events (%) 10 9 8 7 6 5 4 3 2 1 0 557595115135155175195 LDL Cholesterol (mg/dL) y = 0.0599x - 3.3952 R 2 = 0.9305 P=.0019 AFCAPS-S WOSCOPS-S ASCOT-S ASCOT-P AFCAPS-P WOSCOPS-P

4. Cholesterol Trialist Collaboration Meta-Analysis of Dyslipidemia Trials 50% 40% 30% 20% 10% 0% -10% 0.5 1.0 1.5 2.0 Reduction in LDL Cholesterol (mmol/L) Major Vascular Events Proportional Reduction in Event Rate (SE) Adapted from CTT Collaborators. Lancet. 2005; 366:1267-78

5. High-dose statin betterHigh-dose statin worse Odds Reduction Event Rates No./Total (%) High DoseStd Dose -16% 3972/13798 (28.8) 4445/13750 (32.3) -16% 1097/13798 (8.0) 1288/13750 (9.4) -12% 462/13798 (3.3) 520/13750 (3.8) +3% 340/13798 (2.5) 331/13750 (2.4) -6% 808/13798 (5.9) 857/13750 (6.2) -18% 316/13798 (2.3) 381/13750 (2.8) Coronary Death or Any Cardiovascular Event Coronary Death or MI Cardiovascular Death Non-Cardiovascular Death Total Mortality Stroke 0.512.5 OR 0.82 95% CI, 0.71-0.96 p=0.012 Odds Ratio (95% CI) Meta-Analysis of Intensive Statin Therapy All Endpoints OR, 0.94 95% CI, 0.85-1.04 P=0.20 OR, 1.03 95% CI, 0.88-1.20 p=0.73 OR, 0.88 95% CI, 0.78-1.00 p=.054 OR, 0.84 95% CI, 0.77-0.91 p=0.00003 OR, 0.84 95% CI, 0.80-0.89 P=.0000000000006 Cannon CP, et al. JACC 2006; 48: 438 - 445.

6. Coronary Heart Disease (CHD) Event Rates in Secondary Prevention Trials R² = 0.9029 p < 0.0001 LDL Cholesterol (mg/dl) CHD Events (%) PROVE-IT-PR PROVE-IT-AT CARE-S LIPID-S HPS-S 4S-S HPS-P CARE-P LIPID-P 4S-P O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6.