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Presenter Disclosure Information

Presenter Disclosure Information. Paul M Ridker, MD, FACC.

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Presenter Disclosure Information

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  1. Presenter Disclosure Information Paul M Ridker, MD, FACC Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Seimens and AstraZeneca. Dr Ridker is the Principal Investigator of JUPITER, an investigator initiated trial funded by AstraZeneca. Dr Ridker has served as a consultant to AstraZeneca, Novartis, Merck, Schering Plough, ISIS, Vascular Biogenics (modest). Dr Ridker has received grant support from the NHLBI, the NCI, the Donald W Reynolds Foundation, the Doris Duke Foundation, the Leducq Foundation, AstraZeneca, SanofiAventis, Novartis and Merck (significant)

  2. Controversies in Prevention: The JUPITER Trial Will it Change Your Practice?Primary Results and Implications Paul M Ridker, MD, MPH Eugene Braunwald Professor of Medicine Director, Center for Cardiovascular Disease Prevention Brigham and Women’s Hospital Harvard Medical School, Boston, MA USA Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes.

  3. LDLC Levels in 136,905 Patients Hospitalized With CAD: 2000- 2006 LDLC (mg/dL) < 130 130-160 > 160 Sachdeva et al, Am Heart J 2009;157:111-7.e2.

  4. JUPITER Trial Design JUPITERMulti-National Randomized Double Blind Placebo Controlled Trial of Rosuvastatin in the Prevention of Cardiovascular EventsAmong Individuals With Low LDL and Elevated hsCRP MI Stroke Unstable Angina CVD Death CABG/PTCA Rosuvastatin 20 mg (N=8901) No Prior CVD or DM Men >50, Women >60 LDL <130 mg/dL hsCRP >2 mg/L Placebo (N=8901) 4-week run-in Baseline LDLC 104 mg/dL Baseline HDLC 49 mg/dL Baseline hsCRP 4.2 mg/L Women 6,800 Non-Caucasian 5,000 Ridker et al, NEJM 2008359:2195-07

  5. JUPITER Primary Trial Endpoint :MI, Stroke, UA/Revascularization, CV Death HR 0.56, 95% CI 0.46-0.69 P < 0.00001 Placebo 251 / 8901 0.08 Number Needed to Treat (NNT5) = 25 - 44 % 0.06 Cumulative Incidence 0.04 Rosuvastatin 142 / 8901 0.02 0.00 0 1 2 3 4 Follow-up (years) Number at Risk Rosuvastatin 8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 157 Placebo 8,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174

  6. JUPITER Myocardial Infarction, Stroke, Cardiovascular Death HR 0.53, 95%CI 0.40-0.69 P < 0.00001 0.05 Placebo (N = 157) 0.04 - 47 % 0.03 Cumulative Incidence 0.02 Rosuvastatin (N = 83) 0.01 0.00 0 1 2 3 4 Follow-up (years) Number at Risk Rosuvastatin 8,901 8,643 8,437 6,571 3,921 1,979 1,370 998 551 159 Placebo 8,901 8,633 8,381 6,542 3,918 1,992 1,365 979 550 181

  7. JUPITER Fatal or Nonfatal Myocardial Infarction HR 0.45, 95%CI 0.30-0.70 P < 0.0002 0.030 0.025 Placebo 0.020 Cumulative Incidence - 55 % 0.015 0.010 Rosuvastatin 0.005 0.000 0 1 2 3 4 Follow-up Years

  8. JUPITER Fatal or Nonfatal Stroke 0.030 HR 0.52, 95%CI 0.34-0.79 P = 0.002 0.025 Placebo 0.020 Cumulative Incidence 0.015 - 48 % 0.010 Rosuvastatin 0.005 0.000 0 1 2 3 4 Follow-up Years

  9. JUPITER Bypass Surgery / Angioplasty HR 0.54, 95%CI 0.41-0.72 P < 0.00001 0.06 Placebo (N = 131) 0.05 0.04 - 46 % Cumulative Incidence 0.03 0.02 Rosuvastatin (N = 71) 0.01 0.00 0 1 2 3 4 Follow-up (years) Number at Risk Rosuvastatin 8,901 8,640 8,426 6,550 3,905 1,966 1,359 989 547 158 Placebo 8,901 8,641 8,390 6,542 3,895 1,977 1,346 963 538 176

  10. JUPITER All Cause Mortality HR 0.80, 95%CI 0.67-0.97 P= 0.02 Placebo 247 / 8901 0.06 - 20 % 0.05 0.04 Cumulative Incidence 0.03 Rosuvastatin 198 / 8901 0.02 0.01 0.00 0 1 2 3 4 Follow-up (years) Number at Risk Rosuvastatin 8,901 8,847 8,787 6,999 4,312 2,268 1,602 1,192 683 227 Placebo 8,901 8,852 8,775 6,987 4,319 2,295 1,614 1,196 684 246

  11. JUPITER Primary Endpoint – Understudied or “Low Risk” Subgroups Understudied Subgroups N HR (95%CI) Women 6,801 0.54 (0.37-0.80) Age > 70 5,695 0.61 (0.46-0.82) Black, Hispanic, Other 5,117 0.63 (0.41-0.98) “Low Risk” Subgroups Framingham Risk < 10 % 8,882 0.56 (0.38-0.83) 6,269 0.66 (0.47-0.92) LDLC < 100 mg/dL 4,073 0.59 (0.40-0.87) BMI < 25 mg/m2 No Hypertension 7,586 0.62 (0.44-0.87) No metabolic Syndrome 10,296 0.49 (0.37-0.65) Elevated hsCRP Only 6,375 0.63 (0.44-0.92) All Participants 17,802 0.56 (0.46-0.69) 0.25 0.5 1.0 2.0 4.0 Rosuvastatin Superior Rosuvastatin Inferior

  12. JUPITER Primary Endpoint According to Baseline Glucose Levels Impaired Fasting Glucose Normal Fasting Glucose HR 0.69, 95% CI 0.49-0.98 P= 0.04 HR 0.51, 95% CI 0.40-0.67 P < 0.0001 0.10 Placebo Placebo 0.08 0.06 Cumulative Incidence 0.04 Rosuvastatin 0.02 Rosuvastatin 0.00 0 1 2 3 4 0 1 2 3 4 Follow-up Years Follow-up Years

  13. JUPITER Number Needed to Treat (5 year) Endpoint All Primary Endpoint 25 Primary Endpoint, Mortality 22 MI, Stroke, CABG/PTCA, Death 23 MI, Stroke, Death 31 Benchmarks: Statins for hyperlipidemia 5-year NNT 40-60 Diuretics 5-year NNT 80-100 Beta-blockers 5-year NNT 120-160 Aspirin Men 5-year NNT 220-270 Aspirin Women 5-year NNT 280-330

  14. JUPITER Number Needed to Treat (5 year) Endpoint All Men Women Primary Endpoint 25 22 36 Primary Endpoint, Mortality 22 19 33 MI, Stroke, CABG/PTCA, Death 23 19 35 MI, Stroke, Death 31 25 59 Benchmarks: Statins for hyperlipidemia 5-year NNT 40-60 Diuretics 5-year NNT 80-100 Beta-blockers 5-year NNT 120-160 Aspirin Men 5-year NNT 220-270 Aspirin Women 5-year NNT 280-330

  15. JUPITER Number Needed to Treat (5 year) Endpoint All FRS<10 FRS>10 Primary Endpoint 25 47 17 Primary Endpoint, Mortality 22 39 16 MI, Stroke, CABG/PTCA, Death 23 42 16 MI, Stroke, Death 31 67 22 Benchmarks: Statins for hyperlipidemia 5-year NNT 40-60 Diuretics 5-year NNT 80-100 Beta-blockers 5-year NNT 120-160 Aspirin Men 5-year NNT 220-270 Aspirin Women 5-year NNT 280-330

  16. Estimated 5-Year NNT Values for the Primary Prevention of Cardiovascular Disease In Middle-Aged Populations JUPITER WOSCOPS HTN - Diuretics Aspirin - Men Aspirin - Women AFCAPS/TexCAPS HTN – Beta Blockers

  17. JUPITER Can we improve and simplify guidelines for primary prevention? www.reynoldsriskscore.org

  18. JUPITER Can we simplify guidelines for statin therapy? 1. Strong recommendations for diet, exercise, and smoking cessation for any patient with or at risk for cardiovascular disease. 2. If there is prior MI, stroke, or known CVD, treat 3. If the patient is diabetic or has a very strong family history of premature atherothrombosis, treat 4. If LDLC > 160, TC:HDLC > 6, or hsCRP > 2, treat 5. Beyond these recommendations, referral to lipid specialist or cardiologist for further evaluation.

  19. JUPITER ACC 2009 - Late Breaking Clinical Trial Data Do statins have antithrombotic or fibrinolytic effects? Late Breaking Clinical Trials II Sunday 2:00 PM Hall A2 A Randomized Trial of Rosuvastatin in the Prevention of Venous Thormboembolism: The JUPITER Trial Is the benefit observed in the JUPITER trial associated with achieving a low level of LDLC,a low level of hsCRP, or both? Late Breaking Clinical Trials V Monday 2:00 PM Hall A2 Dual Treatment Targets for LDLC and CRP After Initiation Of Rosuvastatin: The JUPITER Trial

  20. JUPITER Public Health Implications Exercise, diet, and smoking cessation remain the first interventions for those with elevated LDLC or hsCRP. However, application of the simple screening and treatment strategy tested in the JUPITER trial over a five-year period could conservatively prevent more than 250,000 heart attacks, strokes, revascularization procedures, and cardiovascular deaths in the United States alone. Simplified guidelines that advocate combined lifestyle and pharmacologic therapy in those groups where trial evidence clearly supports a net benefit have the potential to greatly improve patient care and public health. With thanks to the 17,802 patients and the >1,000 physicians worldwide for their effort and commitment to the JUPITER trial program.

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