Pfizer Talk Final
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1) A 43-year-old male presented with chest pain and was diagnosed with an acute inferior STEMI while in normal sinus rhythm. His medical history included atherosclerosis. 2) Atherosclerosis is caused by plaque buildup in arteries and accounts for over 70% of cardiovascular deaths in the US. Elevated LDL cholesterol increases the risk of atherosclerosis and heart disease. 3) Therapeutic lifestyle changes like diet and exercise can modestly lower LDL cholesterol by about 5% on average but response varies between individuals. High fat, low carb diets may improve glycemic control in diabetes without worsening lipids.
Pfizer Talk Final
- 1. Pfizer Talk Family Medicine 13/1/2010Dr Ihab Suliman
- 2. 43 years old male with Chest Pain
- 3. Acute Inferior STEMI in NSR.
- 6. The Impact of Elevated LDL-C and Associated AtherosclerosisAtherosclerosis is caused by a build-up of plaque in arterial walls, obstructing blood flowAtherosclerosis accounts for more than 70% of all deaths from cardiovascular disease in the USElevated LDL (low-density lipoprotein) cholesterol increases risk of atherosclerosis and coronary heart diseaseThe risk of coronary heart disease increases by about 2% for each 1% elevation in total cholesterolNational Center for Health Statistics. Health, United States, 2005.http://www.cdc.gov/nchs/hus.htm. Accessed May 17, 2006Kwiterovich PO Jr. Am J Cardiol. 1998,82:3U-17U
- 7. Cholesterol is important in so many metabolic activities , there fore it is more important in adults or infants????
- 8. What is the normal Cholesterol level in Infancy???.
- 9. Cholesterol Levels By SpeciesInfantAdult AmericanHunter-GathererHumans:HazdaInuitIKungPygmySanWild Primates:BaboonHowlerMonkeyNight MonkeyWild Mammals:HorseBoarPeccaryBlackRhinocerosAfricanElephantModern Human:507090110130150170190210Mean Total Cholesterol LevelJACC 2004;43:2142-6
- 10. Discovery of statinsSome drugs available but not effectiveIn 1971,Endo and Kuroda (Sankyo Pharmaceuticals in Japan) began search for better drugsCholesterol pathway known and they wanted to find a HMG-CoA reductase inhibitor – looked for a microorganism – screened over 6000Two (3rd later) cmpds identified - one was from Penicillium citrinum - named mevastatinIn 1976 isolated and crystallized Clinical trials started in 1978 and quickly stopped because of animal tumors
- 11. Modifiable Risk FactorsBehavioursCigarette smoking
- 13. Physical inactivity Medical conditionsHypertension
- 16. Obesity
- 18. Cardiac diseasesAtrial fibrillationCoronary artery diseaseCHF
- 19. Causes of death, 2001:USA1. Infectious and parasitic diseases: 14.9 million6.2. Heart diseases: 11.1 million1.3. Cancers: 7.3 million2.4. Stroke: 5.5 million3.5. Respiratory diseases: 3.6 million4.6. Accidents, fires, drowning, etc.: 3.5 million5.7. Maternal and perinatal: 3.0 million8. Violence (war, homicide, suicide): 1.6 million Population: 6,122,210,000Deaths: 56,554,000World Health OrganizationWorld Health Report 2002
- 20. Therapeutic lifestyle change is the cornerstone of the management of hyperlipidemia and dyslipidemia? LDL-C with AHA diet: ~ 5%Response variability: familial/geneticHypocaloric diets in overweight & obese
- 21. A high fat, low carb diet does not worsen serum lipids/lipoproteins and improves glycemic control in patients with diabetesLDL-C is unchangedHDL-C is unchanged or slightly higherTriglyceride is lower by~25%Variability in response?HbA1c better than with LFHC diet
- 22. Dietary NuancesFish: twice/wk; omega-3 fatty acids, 1000 mg/dEliminate/reduce trans FA Plant stanols/sterols reduce LDL-C by ~10%Antioxidant vitamins are not cardioprotective and interfere with effects of niacin on HDL-CHomocysteine: folic acid, vitamins B6 and B12not proven to be cardioprotective.
- 23. The 2004 NCEP LDL-C goal:lower may be betterAcute Coronary SyndromesMIRACL: LDL-C, 125 72 mg/dl
- 24. PROVE-IT: LDL-C, 106 62 mg/dlStable CHDHPS: benefit if basal LDL-C
- 25. ALLIANCE: 111 95 mg/dl
- 26. REVERSAL: 150 79 mg/dlHow low a LDL-C is safe?Newborn LDL-C is 35-50 mg/dl.Patients with hypobetalipoproteinemia are healthy and have enhanced survival
- 27. ATP III Treatment PrioritiesReduce LDL-C to goal (new goals)Correct residual lipid/lipoprotein abnormalities( non-HDL-cholesterol)Address the metabolic syndrome
- 28. Utility of the non-HDL-cholesterolTotal minus HDL-CIncludes all atherogenic lipoproteinsLDL-C, Lp(a), IDL, VLDLSurrogate for apoprotein BOptimum; add 30 mg/dl to LDL-C goals
- 29. All patients should receive TLC advise. Simultaneous drug therapy should be started in:Patients with symptomatic CHDAll high risk patientsIntermediate risk men@40-45 yrs
- 30. women@50-55 yrsOptions for reducing LDL-cholesterolStatins
- 32. Bile acid binding resins
- 33. NiacinMuscle Adverse EffectsMyalgiaWeaknessFatigueMyopathy without CKPredisposing factors:Combined hyperlipidemia
- 35. Suboptimum thyroxine replacementMODIFY RISK FACTORS
- 36. Hyperlipidemia in PregnancyTC & TG levels increase throughout pregnancyaverage cholesterol increase: 30 to 40 mg/dL around weeks 36 to 39TGs may increase as much as 150 mg/dLDrug therapy typically not initiated/continued during pregnancyTLC is the mainstay but BARs & absorption inhibitors may be considered in high risk patientsezetimibe: category C Statins: category X24
- 37. Statin Therapy Can Reduce the Risk of Coronary Heart Disease (CHD)Friday KE. Exp Biol Med. 2003,228:769-778Wilt TJ et al. Arch Intern Med. 2004;164:1427-1436
- 38. Diabetic DyslipidemiaCharacterized by hypertriglyceridemia, low HDL, & minimally elevated LDLDM ATP III CHD risk equivalentSmall, dense LDL (pattern B) in DM patients is more atherogenic than larger, more buoyant LDL (pattern A)1˚target: LDL Goal of treatment: LDL-C < 100 mg/dLLDL > 130 mg/dL: TLC + drug therapy often required Statins often considered initial drugs of choice26Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497.
- 39. Diabetic DyslipidemiaCollaborative AtorvastatinDiabetes Study (CARDS)LDL lowering for 1˚ CHD prevention in type 2 DMRandomized, double-blinded placebo controlledAtorvastatin 10 mg/day versus placebo (n=2,838) diabetes to reduce first CHD events Baseline LDL: 118 mg/dL; LDL ↓ 46 mg/dL with atorvastatin27Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet 2004;364:685–696.
- 40. Collaborative Atorvastatin Diabetes Study (CARDS)Atorvastatin 10 mg (n=1428)Patient PopulationType 2 diabetes mellitusMen and women 40–75 years of agePrimary CHD and stroke preventionLDL-C 160 mg/dL (4.14 mmol/L)TG 600 mg/dL (6.78 mmol/L)1 additional RFHTN (or on HTN treatment)RetinopathyAlbuminuriaCurrent smoking2838 patients4-year follow-upDouble-blind placebo (n=1410)Primary endpoint: time to first major CV event (CHD death, nonfatal MI, unstable angina, resuscitated cardiac arrest, coronary revascularization, stroke
- 41. Secondary endpoints: total mortality, any CV endpoint, lipids, and lipoproteinsColhoun HM et al. Lancet 2004;364:685-696.
- 42. CARDS: Patient Baseline CharacteristicsColhoun HM et al. Lancet 2004;364:685-696. Reprinted with permission from Elsevier.
- 43. CARDS: Patient Baseline Lipids*Median (interquartile range)Colhoun HM et al. Lancet 2004;364:685-696. Reprinted with permission from Elsevier.
- 44. 012344.5012344.5CARDS: Lipid Levels by TreatmentTotal Cholesterol (mg/dL)Average difference 26%,54 mg/dL; P<0.0001LDL Cholesterol (mg/dL)Average difference 40%,46 mg/dL; P<0.0001PlaceboPlaceboMedian LDL-C (mg/dL)*AtorvastatinMedian TC (mg/dL)*AtorvastatinYears of StudyYears of StudyColhoun HM et al. Lancet 2004;364:685-696. Reprinted with permission from Elsevier.
- 45. CARDS: Effect of Atorvastatin on the Primary Endpoint: Major CV Events Including StrokeRelative Risk Reduction 37% (95% CI, 17–52)P = 0.001Placebo127 eventsCumulative Hazard, (%)Atorvastatin83 events012344.75Years1410142813511392PlaceboAtorvastatin1306136110221074651694305328Colhoun HM et al. Lancet 2004;364:685-696. Reprinted with permission from Elsevier.
- 46. CARDS: Adverse and Serious Adverse EventsColhoun HM et al. Lancet 2004;364:685-696.
- 47. Diabetic DyslipidemiaCARDS trial: 37% reduction in composite 1˚end point1˚ endpoint: acute CHD death, nonfatal MI, hospitalized unstable angina, resuscitated cardiac arrest, coronary revascularization, or strokeSuggests diabetics should have target LDL much lower than 100 mg/dL34Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet 2004;364:685–696.
- 48. Atorvastatin 10 mg Number of events 100Placebo Number of events 154436% reduction3Cumulative Incidence (%) 21HR = 0.64 (0.50-0.83)P = 0.000500.00.51.01.52.02.53.03.5YearsASCOT: Primary Endpoint: Nonfatal MI/Fatal CHDSever PS et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158.
- 49. Comparing 2 statin drugsAtarvastatin – 80 mg.Pravastatin – 40 mg.Equivalent dosesTrial was designed to demonstrate non-inferiority of pravastatin. Instead, it showed ataravastatin to be superior.Not only did ataravastatin lower cholesterol more (and faster), but it lowered death rate by 16%Study was stopped “early.”
- 50. FDA 2007The FDA approved atorvastatin for reducing the risk for nonfatal MI, reducing the risk for fatal and nonfatal strokes, for use in certain types of heart surgery, for reductions in the risk of hospitalization for heart failure, and to reduce chest pain in patients with heart disease. Atorvastatin is the first cholesterol-lowering drug to be approved for reducing the risk of hospitalization for heart failure.
- 51. Thank You Very Much