Insights from clinical trials : The unassailable case for LDL-c lowering

1. Master class: Exploring the clinical innovations in lipid management? June 4-5, 2010, Barcelona Insights from clinical trials:The unassailable case forLDL-c lowering Kausik Ray, MD St Georges University London, United Kingdom

2. 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 WithOn-Treatment LDL-Cholesterol Levels 10 y = 0.0599x - 3.3952 R2 = 0.9305 P=.0019 9 8 WOSCOPS-P 7 WOSCOPS-S 6 AFCAPS-P CHD Events(%) 5 AFCAPS-S 4 3 ASCOT-P 2 ASCOT-S 1 0 -1 55 75 95 115 135 155 175 195 LDL Cholesterol (mg/dL) P = placebo; S = statin. Reproduced from O'Keefe et al. J Am CollCardiol. 2004;43:2142, with permission.

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

5. Meta-Analysis of Intensive Statin Therapy All Endpoints Odds Ratio (95% CI) OR, 0.84 95% CI, 0.80-0.89 P=.0000000000006 OR, 0.84 95% CI, 0.77-0.91 p=0.00003 OR, 0.88 95% CI, 0.78-1.00 p=.054 OR, 1.03 95% CI, 0.88-1.20 p=0.73 OR, 0.94 95% CI, 0.85-1.04 P=0.20 OR 0.82 95% CI, 0.71-0.96 p=0.012 0.5 1 2.5 High-dose statin better High-dose statin worse Cannon CP, et al. JACC 2006; 48: 438 - 445.

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