Published on

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide


  1. 1. Difference of Opinion leads to Inquire, and inquire leads to truth (Thomas Jefferson)
  2. 2. • Recent Tv Talk Shows. • Test Cricket Match • Pharmaceutical Presnetation. Cardiology in Review • Volume 14, Number 2, March/April 2006
  3. 3. • South Asians have a higher prevalence of CAD as compared with other ethnicities. • South Asians may have a genetic predisposition to CAD • Environmental, nutritional, and lifestyle factors may also be responsible. Cardiology in Review • Volume 14, Number 2, March/April 2006
  4. 4.  Higher prevalence of: ◦ metabolic syndrome, ◦ Diabetes, insulin resistance ◦ Central obesity ◦ Dyslipidemias ◦ Increased lipoprotein ◦ Higher triglyceride levels ◦ Increased thrombotic tendency (increased plasminogen activator inhibitor-1 ◦ Decreased tissue plasminogen activator levels) and decreased levels of physical activity. Cardiology in Review • Volume 14, Number 2, March/April 2006
  5. 5.  STUDY CONDUCTED AT: Cardiology Department; The National Institute of Cardiovascular Diseases (NICVD), Karachi.  Dr. Mazhar Mahmood, Dr. Tariq Ashraf, Dr Mohammad Anis Memon, Dr. Abdul Samad Achakzai,
  6. 6.  Major, independent risk factors  Life-habit risk factors  Emerging risk factors National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines
  7. 7.  Obesity (BMI 30)  Physical inactivity  Atherogenic diet National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines
  8. 8.  Lipoprotein (a)  Homocysteine  Prothrombotic factors  Proinflammatory factors  Impaired fasting glucose  Subclinical atherosclerosis National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines
  9. 9.  Cigarette smoking  Hypertension (BP 140/90 mmHg or on antihypertensive medication)  Low HDL cholesterol (<40 mg/dL)†  Family history of premature CHD ◦ CHD in male first degree relative <55 years ◦ CHD in female first degree relative <65 years  Age (men 45 years; women 55 years) National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines
  10. 10. In ATP III, diabetes is regarded as a CHD risk equivalent. † HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count. National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines
  11. 11. Risk Category CHD and CHD risk equivalents Multiple (2+) risk factors Zero to one risk factor LDL Goal (mg/dL) <100 <130 <160 National Cholesterol Education Program Adult Treatment Panel III (ATP III) Guidelines
  12. 12. Most Patients Do Not Reach NCEP ATP III Target Patients reaching NCEP ATP II LDL cholesterol target (%) Pearson TA et al. Arch Intern Med. 2000;160:459-467. Low-risk (n=1143) High-risk (n=2285) CHD (n=1460) All patients (N=4888) 68 37 18 38 0 20 40 60 80 100
  13. 13. 0 10 20 30 40 50 60 70 80 90 100 LDL-C Non-HDL-C Patients,%atgoal Atorvastatin 10 - 80 mg Simvastatin 10 - 40 mg Lovastatin 20 - 80 mg Fluvastatin 20 - 80 mg Pravastatin 10 - 40 mg †Patients in CHD risk category. Ballantyne CM, et al. Am J Cardiol. 2001;88:265-269. n = 2,543† At Wk 54
  14. 14. Proportions of patients achieving ATP III LDL-C goal <100 mg/dL at 16 weeks after switching to rosuvastatin (RSV) or remaining on atorvastatin (ATV) or simvastatin (SIM) after 8 weeks. *P < .001 for within-arm comparison of rosuvastatin vs atorvastatin or simvastatin.
  15. 15. C-Reactive Protein, a Sensitive Marker of Inflammation, Predicts Future Risk of Coronary Heart Disease in Initially Healthy Middle-Aged Men Results From the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992 Conclusions—These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications. (Circulation. 1999;99:237-242.)
  16. 16. Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention Paul M Ridker ISSN: 1524-4539 Circulation 2003, 107:363-369 • Composed of five 23 kDa subunits, C-reactive protein (CRP) is an hepatically derived pentraxin that plays a key role in the innate immune response. • CRP has a long plasma half-life and is now understood to be a mediator as well as a marker of atherothrombotic disease. • Epidemiological studies carried out among individuals with no prior history of cardiovascular disease demonstrate that a single, non-fasting measure of CRP is a strong predictor of future vascular events
  17. 17. JUPITER Background and Prior Work Current guidelines for the prevention of myocardial infarction stroke, and cardiovascular death endorse statin therapy among patients with established vascular disease, diabetes, and among those with hyperlidemia. However, these screening and treatment strategies are insufficient as half of all heart attack and stroke events occur among apparently healthy men and women with average or even low levels of cholesterol. Ridker et al NEJM 2008
  18. 18. JUPITER AHA November 9, 2008 A Randomized Trial of Rosuvastatin in the Prevention of Cardiovascular Events Among 17,802 Apparently Healthy Men and Women With Elevated Levels of C-Reactive Protein (hsCRP): The JUPITER Trial Paul Ridker*, Eleanor Danielson, Francisco Fonseca*, Jacques Genest*, Antonio Gotto*, John Kastelein*, Wolfgang Koenig*, Peter Libby*, Alberto Lorenzatti*, Jean MacFadyen, Borge Nordestgaard*, James Shepherd*, James Willerson, and Robert Glynn* on behalf of the JUPITER Trial Study Group
  19. 19. JUPITER Primary Objectives To investigate whether rosuvastatin 20 mg compared to placebo would decrease the rate of first major cardiovascular events among apparently healthy men and women with LDL < 130 mg/dL (3.36 mmol/L) who are nonetheless at increased vascular risk on the basis of an enhanced inflammatory response, as determined by hsCRP > 2 mg/L. Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin Ridker et al NEJM 2008
  20. 20. Rosuvastatin 20 mg (N=8901) MI Stroke Unstable Angina CVD Death CABG/PTCA JUPITER Multi-National Randomized Double Blind Placebo Controlled Trial of Rosuvastatin in the Prevention of Cardiovascular Events Among Individuals With Low LDL and Elevated hsCRP 4-week run-in Ridker et al, Circulation 2003;108:2292-2297. No Prior CVD or DM Men >50, Women >60 LDL <130 mg/dL hsCRP >2 mg/L JUPITER Trial Design Placebo (N=8901) Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica, Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands, Norway, Panama, Poland, Romania, Russia, South Africa, Switzerland, United Kingdom, Uruguay, United States, Venezuela
  21. 21. JUPITER Primary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death Placebo 251 / 8901 Rosuvastatin 142 / 8901 HR 0.56, 95% CI 0.46-0.69 P < 0.00001 - 44 % 0 1 2 3 4 CumulativeIncidence Number at Risk Follow-up (years) Rosuvastatin Placebo 8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 157 8,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174 Ridker et al NEJM 2008
  22. 22. JUPITER Conclusions – Efficacy I Among apparently healthy men and women with elevated hsCRP but low LDL, rosuvastatin reduced by 47 percent incident myocardial infarction, stroke, and cardiovascular death. Despite evaluating a population with lipid levels widely considered to be “optimal” in almost all current prevention algorithms, the relative benefit observed in JUPITER was greater than in almost all prior statin trials. In this trial of low LDL/high hsCRP individuals who do not currently qualify for statin therapy, rosuvastatin significantly reduced all-cause mortality by 20 percent. Ridker et al NEJM 2008
  23. 23. JUPITER Conclusions - Safety • With regard to safety , the JUPITER results • show no increase in serious adverse events among those allocated to rosuvastatin 20 mg as compared to placebo in a setting where half of the treated patients achieved levels of LDL< 55 mg/dL (and 25 percent had LDL < 44 mg/dL). • show no increase in myopathy, cancer, hepatic disorders, renal disorders, or hemorrhagic stroke with treatment duration of up to 5 years • show no increase in systematically monitored glucose or glucosuria during follow-up, but small increases in • HbA1c and physician reported diabetes similar to that seen in other major statin trials Ridker et al NEJM 2008
  24. 24. JUPITER Implications for Primary Prevention Among men and women age 50 or over : If diabetic, treat If LDLC > 160 mg/dL, treat If hsCRP > 2 mg/L, treat A simple evidence based approach to statin therapy for primary prevention. Ridker et al NEJM 2008
  25. 25.  Patients who qualify for statin therapy are either not being treated, being under-treated, or both.  Aggressive lipid lowering beyond current guidelines appears to be more efficacious in reducing morbidity & mortality.  Rosuvastatin is the most potent member of statin family that has ability to regress Atherosclerosis.
  26. 26. Thank You