secondary prevention of cardiac disease

1. Secondary Prevention of Cardiac Disease Long term management strategies in the outpatient setting for CAD patients

3. Treatment Goals Reduce or eliminate symptoms Decrease the risk of MI Mortality reduction

4. Case Claude A. Darwin 50 year old male Presents for routine follow-up Heart cath last month -mild to moderate 2 vessel CAD - �medical therapy & risk factor modification recommended�

5. No symptoms of chest pain or shortness of breath No allergies reported No routine medications

6. First Question Are you taking Aspirin?

7. Answer �YES � 81mg a day� Common misperception is that ASA does not count as a medicine and as a result is often not included on a patient�s medicine list

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10. Felix Hoffman

11. Present formulation was developed in Europe in the 1800�s Bayer Co. patent 1899 Initially used as a treatment for pain and inflammation Anti platelet effects became known in 1970�s Clinical trails (70�s & 80�s): Decrease in MI risk by 25%

12. ASA Irreversibly inhibits cyclooxygenase Results in a decreased synthesis of Thromboxane A2 Decrease Thromboxane A2 = decrease in platelet aggregation

13. ASA Inexpensive Dose: 75-325mg a day Downsides: -GI side effects -Bruising Allergy vs. Intolerance

14. After discovering that Claude is taking ASA 81mg a day and tolerating it well, we encourage him to continue We add ASA 81mg a day to his medicine list

15. Claude Asks: �I saw an ad on TV last night about a medicine called Plavix � should I be taking it?�

16. Plavix Approved for use in the United States in 1997 Prevents ADP mediated activation of platelets by inhibiting the binding of ADP to platelet receptors ADP activates IIb/IIIa complex

17. Trial Data: CAPRIE (Lancet 1996) � Clopidogrel vs. ASA in pts at risk for ischemic events 19K pts (MI, CVA, Vas dz) CURE (NEJM 2001) � Clopidogrel in USA to prevent recurrent events 12.5K pts (ACS/NSTMI) ASA + Plavix vs. ASA + Placebo 1 yr: 20% rel risk reduction

18. COMMIT (NEJM 2005) � Clopidogrel and Metoprolol in Myocardial Infarction Trial 46K Pts (Acute MI ; China) Plavix vs. Placebo Improved outcomes on top of med rx inc ASA CLARITY (NEJM 2005) � Clopidogrel as Adjunctive Reperfusion Therapy 3.5K Pts (STEMI � TT/ASA) 20% risk reduction CHARISMA (NEJM 2006) � Clopidogrel for high atherosclerotic risk and ischemic stabalization 15.5K Pts (CVdz & RF) ; ASA vs. ASA + Plavix Negative trial

19. PLAVIX Use as a substitute for ASA if there is a true allergy or intolerance Should be combined with ASA if patient has experienced a recent MI/ACS or if Stent placement Downsides: -Cost: $100 per month -Bleeding risk / surgery delay

20. Physical Exam BP = 150/70 HR = 90 WT = 230 Lungs: CTA : No wheezes Heart: RR & R without murmur Extrem: No edema

21. Hypertension Continuous positive relationship between both systolic and diastolic BP and CAD For each 20 mm Hg rise in SBP or 10 mm Hg in DBP = doubles the risk of Cardiovascular dz Mechanism: Direct vascular injury, increased wall stress, increase in myocardial oxygen demand

22. BP Goals JNC VII guidelines � 2003 < 140/90 or < 130/80 (DM or RI) All ages benefit from BP reduction (absolute benefit in older pts maybe 2X that in younger pts) BP control with anti-HTN meds results in a 20 � 25% decease in MI risk

23. Large number of BP meds to choose from Multiple classes and multiple options within this class The eventual regiment used must be tailored to that specific patient�s situation to provide not only adequate BP control but also good tolerability

24. Beta Blockers Good first choice in CAD pts Well tolerated; good safety profile Decreased risk of dysrhythmias Anti-anginal effect Low cost

25. Beta Blockers cont. Coreg or Toprol XL should be considered in CAD pts with reduced EF Downsides to Beta Blockers - Decreased heart rate / AV Block - Active wheezing - Side effects: fatigue / impotence

26. ACE Inhibitors Inhibit Angiotensin converting enzyme resulting in a decrease in the conversion of angiotensin I to angiotensin II Generally well tolerated Affordable Multiple choices within the class

27. HOPE TRIAL �Heart outcomes prevention evaluation� Published NEJM 2000 9.5K pts: vast majority with CAD Placebo controlled, randomized, double blind Altace 10mg a day vs. placebo 22% relative reduction in MI / death Curves still diverging after 3 yrs

28. Consider ACE-I especially in CAD pts with decreased EF or DM Downsides: - Caution in pts with RI - 20% dry cough - rare angioedema Alternative class: ARB ONTARGET Trial: Altace 10mg vs. Micardis 80mg

29. Claude BP = 150/70 HR = 90 No wheezes on exam Beta Blocker

30. Nitrates In use since 1800�s Endothelium independent vasodilator Decrease myocardial oxygen demand by decreasing LV volume and preload Increase myocardial perfusion Anti-thrombotic & anti-platelet effects

31. Nitrates cont. Excellent anti-anginal agent Multiple formulations: SL, spray, topical, immediate and sustained release PO Nitrate free interval Downsides: -Headache -Viagra use

32. Claude No symptoms of chest pain or shortness of breath therefore angina is not an issue Consider a script for PRN use of SL or spray

33. After reviewing the heart cath findings with Claude, he asks: �Doc is there anything we can do to reduce the blockage in my arteries?�

34. Statin Therapy REVERSAL Trial: �Reversing Atherosclerosis with Aggressive Lipid Lowering� Published 2004 JAMA 502 Pts � Stable CAD � 18 months Decrease in plaque by IVUS with Lipitor 80mg a day

35. Over the last 10 � 20 yrs, a large body of clinical trials have been completed all showing positive clinical outcomes for CAD pts treated with statins Mechanisms of action: Decrease in LDL cholesterol, decrease in inflammation

36. Number of different statins to choose from Some are generic All pts with documented CAD should be considered for statin therapy

37. Downsides of statin therapy: Rare Rhabdo Rare increase in LFTs Non specific side effects: Headache, nightmares, fatigue, etc�. Most common reason for discontinuation is muscle aches: consider alternate statin, decrease dose, pulse dosing or Co-Q

38. Claude then ask: �I had a friend who takes fish oil capsules � Should I be taking these?�

39. Eskimo Population: 15gm of fish oil / day in native diet

40. Fish oil contains omega 3 fatty acids which are a type of polyunsaturated fatty acid 3 types: - EPA eicosapentaenoic acid - DHA ducosahexanaic acid -LNA alpha-linolenic acid

41. Possible mechanisms of actions: Decrease Thomboxane A2 which results in a decrease in platelet aggregation Decrease in plaque secondary to a decrease in cell growth factors and migration of myocytes Increase in synthesis of NO by endothelium

42. GISSI Prevention Trial Gruppo Italiano per lo Studio della Supravvivenza nell�Infarto Published Circulation 2002 11K pts; post MI; 3yr follow-up 850mg per day of omega 3 20% decrease in cardiac death rate compared with placebo

43. JELIS Study Japan Eicosapentaenoic acid lipid intervention study Published in Lancet 18.5K pts; 4.5 yrs follow-up 1800mg omega 3 + statin vs. placebo + statin 19% risk reduction in coronary events

44. SCIMO Trial �Study on Prevention of Coronary Atherosclerosis by Intervention With Marine omega-3 Fatty Acids� Germany; 1999 � Annals of Internal Medicine Angiographic trial 223 pts with CAD; omega 3 vs. placebo Decrease in CAD progression over 2 yrs

45. Fish Oil Overall weight of evidence suggest that fish oil supplements are useful in pts with CAD Dose suggested: 1-4gm per day Inexpensive / easily available Downsides: -Fishy smell and taste -Doses greater than 4gms per day may rarely increase bleeding tendencies

46. Social History This is a critical area for intervention in the pt with CAD Discussing lifestyle issues can have a huge impact on pts long term outcome

47. At each visit assess smoking status Smoking is a recipe for an MI -increases fibrinogen -increases platelet adhesion -increases vasoconstriction

48. Strategies for Success Counseling: Repetition / persistence Elicit family support Emphasize potential benefits: more energy, less shortness of breath, cite study data (30 -50% decrease in risk of death after MI / CABG) Medical support: Nicotine gum, patch, Wellbutrin, Chantix Long term maintenance and encouragement

49. Activity Assess pts baseline activity level Pedometers can be useful to quantify activity level by steps per day: <5K � sedentary 5 - 7.5K � low activity 7.5 - 10K � some activity 10 - 12K � Active >12.5K � Highly Active

50. Identify activities the patient enjoys Encourage family, friends and community support Cardiac Rehab programs -Low cost -Often covered by insurance -Builds confidence and expands patient�s understanding

51. Nutrition / Diet Another key part of the social history Calorie restriction and exercise = weight reduction Encourage a decease in fat content (esp saturated fats) Increase dietary fiber (whole grains, vegetables, nuts): at least 20-30gms per day

52. Key Approach Individualize these recommendations & Apply to the patient�s lifestyle

53. We start by asking Claude: What is his typical meal schedule? What foods does he usually eat?

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55. Have it your way!

56. Order the plain baked potato instead of large fries Order the grilled chicken sandwich instead of the whooper Try eating salad with dressing on the side instead of covering the salad For a change of pace go to Wendy�s and order the Chili instead of the double stack burger

57. Nutrition / Diet Set goals to measure progress Be realistic and set obtainable bench marks 2 lb weight loss per week 5- 8 lbs per month

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59. Alcohol The issue of alcohol use is a critical part of any social history Try to quantify the patient�s intake

60. There is an inverse relationship between light to moderate alcohol use (1-3 drinks per day) and the risk of cardiac events This conclusion is based on multiple observational studies � no placebo controlled randomized studies � therefore no cause and effect can be established Potential mechanisms: increase in HDL, flavinoids, anti-oxidants, decrease in platelet adhesion

61. AHA: Do not suggest to patients to start drinking as a form of secondary prevention Reasoning: Many patients have difficulty in limiting their intake to the moderate range

62. Summary of ETOH Recommendations If the patient does not drink: Great! If the patient drinks in the light to moderate range: Great! Heavy ETOH use: Counseling

63. Ranexa (Ranolazine) New class of medicine Approved by the FDA Jan. 2006 Indication: Treatment of angina in patients with CAD who are symptomatic despite standard medical therapy

64. CARISA Trial �Combination Assessment of Ranolazine in Stable Angina� JAMA 2004 Randomized placebo controlled double blind ETT assessment: exercise duration, time to angina, time to ischemia Positive trial

65. ERICA Trial �Evaluation of Ranolazine in Chronic Angina� JACC 2006 Randomized placebo controlled double blind Positive Trial for decrease in angina on top of standard medical therapy

66. RANEXA Standard dose: 500mg bid � 1000mg bid Mechanism of action: Reduction of calcium overload in the ischemic myocyte Most common side effects: Constipation (6%), nausea (4%), dizziness (4-5%)

67. Downsides to Ranexa: No mortality benefit Cost Drug-Drug interactions Avoid verapamil, ketoconazole, HIV protease inhibitors since they increase ranexa levels Ranexa tends to increase dig levels (1.5 � 2X) Half the Zocor dose since Ranexa doubles the concentration

68. Chelation Process of IV administration of agents that remove heavy metals from the body Multiple chelating agents are in use (EDTA) Accepted treatment for poisoning with mercury, iron, lead, uranium, plutonium

69. Some practitioners have advocated its use in treatment of coronary dz Typical course is a series of thirty treatments over a period of 2 months Cost is $100-150 per treatment

70. CALGARY Patch Trial �Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health� JAMA 2002 Randomized placebo controlled double blind 84 pts with CAD Negative trial -Time to ischemia on ETT -Exercise capacity -Quality of Life

71. Downsides to Chelation: Cost $3000- 5000. All major medical societies (AMA,ACP,ACC) as well as the FDA state that there is no evidence to support a benefit May result in zinc and calcium depletion

72. Summary In treating patients with coronary disease: Avoid tendency to under treat Use all the tools and interventions at our disposal Consider a check list approach: ASA, Beta Blockers, Statin, Smoking Cessation, exercise

73. THE END