1. AHA Secondary Prevention Guidelines “Get with the Guidelines” And MORE… Timothy A. Denton, M.D., F.A.C.C. High Desert Heart Institute Victorville, CA

2. AHA/ACC Scientific Statement AHA/ACC Guidelines for Secondary Prevention in Patients with Coronary and Other Vascular Disease: 2001 Update Sidney C Smith, Steven N Blair, Robert O Bonow, Lawrence M Brass, Manuel D Cerqueira, Kathleen Dracup, Valentin Fuster, Antonio Gotto, Scott M Grundy, Nancy Houston Miller, Alice Jacobs, Daniel Jones, Ronald M Krauss, Lori Mosca, Ira Ockene, Richard C Pasternack, Thomas Pearson, Marc A Pfeffer, Rodman D Starke, Kathryn A Taubert Circulation 2001;104:1577-1579 www.americanheart.orgwww.acc.org

3. To Which Patients do the Guidelines apply? Coronary artery disease Carotid disease Peripheral vascular disease Abdominal aortic aneurysm Diabetics

4. ABC 2 The Guidelines DM Cigs Exercise BMI HTN

5. Antiplatelet / anticoagulant therapy Intervention recommendations: –Start and continue indefinitely aspirin 75–325 mg/d if not contraindicated. –Consider clopidogrel 75 mg/d or warfarin if aspirin contraindicated. –Manage warfarin to INR=2.0 to 3.0 in post-MI patients when clinically indicated or for those unable to take aspirin or clopidogrel. AHA Secondary Prevention Guidelines 2001

6. GWTG and MORE… What is the correct dose of aspirin? Acute MI – 162-325 mg Secondary prevention – 75-162 mg AHA/ACC MI Guidelines Circulation 2004;110:588

7. GWTG and MORE… How long should we give clopidogrel? Addition of clopidogrel to ASA (75-325) after ACS reduces death+MI+CVA at 1 year (curves continue to diverge, CURE trial) Circulation 2004;110 – to be published

8. GWTG and MORE… What about warfarin? Meta-analysis: ASA + warfarin in ACS 29-45% reduction in mortality J Inv Cardiol 2004;16:271 RCT: warfarin+ASA vs ASA post MI 29% reduction in death+MI+CVA NEJM 2002;347:969

9. Beta blockers Start in all patients post MI and post ACS Continue indefinitely Observe usual contraindications. Use as needed to manage CHF, angina, rhythm, or blood pressure in all other patients. AHA Secondary Prevention Guidelines 2001

10. GWTG and MORE… How aggressive can we be with beta blockers? Using CARDIOSELECTIVE beta-blockers There was no change in FEV1 or COPD exacerbations (up to 12 weeks). Atenolol, bisoprolol, metoprolol block β 1 > β 2 20:1 Salpeter et al. Ann Int Med 2002;137:715 “…unfounded fears…”

11. ACE inhibitors Treat all patients indefinitely post MI Consider use in all patients with coronary or other vascular disease Early use in anterior MI, previous MI, Killip Class II (S 3 gallop, rales, radiographic CHF) AHA Secondary Prevention Guidelines 2001

12. Benefits in HOPE 9,541 subjects randomized to ramipril 10 mg/day or placebo and vitamin E 400 Units/day or placebo for 5 years Terminated early at 4.5 years All patient subgroups had benefit with ACEI. Primary endpoint (MI, stroke, or death from cardiovascular causes) was significantly reduced by 22% with ramipril. Risk reduction with ramipril was evident at 1 year and statistically significant at 2 years. Vitamin E arm showed no benefit. HOPE Study Investigators. N Engl J Med 2000;342:145–160.

13. GWTG and MORE… ACE and ARB More data on ARBs primary HTN No “HOPE” equivalent, yet CHF if reaction to ACE Some CHF data coming out now

14. Can you identify these?

15. Lipid management LDL-cholesterol goal < 100 mg/dl Statins as first line therapy for LDL lowering If LDL low but HDL < 40 mg/dl, consider fibrate or niacin as first line therapy (especially in diabetes) If TG’s are high, do not use a resin TG 200-499, use fibrate/niacin after statins TG >500, use fibrate/niacin before statins Omega-3 FA’s for high TG’s AHA Secondary Prevention Guidelines 2001

16. REVERSAL P=0.02 Nissen JAMA 2004;291:1071 Reversal of Atherosclerosis with Aggressive Lipid Lowering DB Random atorv v. prava (79 v. 110) IV US Atheroma vol

17. ASCOTT-LLA P=0.0005 Nissen JAMA 2004;291:1071 Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm 19,342 HTN + 3 RF Tchol < 250 Atorva v placebo trial stopped 3.3 yrs P=0.024 P=0.0005 P=0.16

18. ACCESS Smith Phamacoeconomics 2003;21:13 Atorvastatin Comparative Cholesterol Efficacy and Safety Study 3,387 54 weeks Atorva, fluva, lova, prava, simva titrate to LDL < 100 DrugTotal Cost to Goal Atorva683.37 fluva+211.35 lova+607.96 Prava+424.60 simva+95.74

19. HPS—Simvastatin: Vascular Events by Baseline LDL-C 358 (21.0%)282 (16.4%)<100 871 (24.7%)668 (18.9%)100–129 2585 (25.2%)2033 (19.8%)All patients 1356 (26.9%)1083 (21.6%)  130 Placebo (n=10,267) Statin (n=10,269) Baseline LDL-C (mg/dL) Event rate ratio (95% CI) Statin better Statin worse 0.40.60.81.01.21.4 www.hpsinfo.org 0.76 (0.72–0.81) p<0.0001

20. CARDS Colhoun et al. Lancet 2004;364:685-696 Collaborative Atorvastatin Diabetes Study 2,838 diabetics, no prior CV disease atorvastatin 10 mg vs placebo 3.9 years, terminated 2 years early

21. GWTG and MORE… It’s not 100 anymore, it’s 70! Grundy et al. Circulation 2004;110:227 Known CAD or DM “optional” LDL goal of <70 mg/dl Based on new trials HPS ALLHAT PROVE-IT ASCOT-LLA PROSPER Two trials to come SEARCH TNT

22. Diabetes Measure Hgb A1c Appropriate hypoglycemic therapy to achieve near-normal plasma glucose as determined by Hgb A1c < 7.0 Treatment of other risks (weight, activity, BP, lipids) AHA Secondary Prevention Guidelines 2001

23. ADA Standards of Medical Care for Patients with Diabetes Glycemic control: Hb A1C <7% Blood pressure control: <130/80 mm Hg Target lipid levels: LDL-C <100 mg/dL HDL-C >45 mg/dL in men, >55 mg/dL in women TG <150 mg/dL Smoking cessation ADA. Diabetes Care 2002;25:S33–S49.

24. But…tight glycemic control has little effect on survival You get more SURVIVAL benefit in diabetics if you start: A Statin An ACE inhibitor ADA. Diabetes Care 2002;25:S33–S49.

25. Smoking Goal is complete cessation Avoid second hand smoke Provide: counseling tobacco cessation programs pharmacologic therapy including nicotine replacement and buproprion AHA Secondary Prevention Guidelines 2001

26. Doll et al. BMJ 1994;309:901-911 Survival Effects of Cigarette Smoking Overall Survival All levels of smoking

27. Physical activity GOAL Minimum: 30 minutes 3–4 days/week Optimal: daily Intervention recommendations: Assess risk, preferably with exercise test, to guide prescription. Encourage minimum of 30–60 minutes of activity (walking, jogging, cycling, or other aerobic activity), preferably daily or at least 3–4 times weekly. Supplement with increased daily lifestyle activities (walking breaks at work, gardening, household work). Advise medically supervised programs for moderate- to high-risk patients. AHA Secondary Prevention Guidelines 2001

28. Exercise Myers, NEJM 2002;346:793 6,213 men ETT for clinical reasons 2,534 normal 3,679 with CAD Mean f/u 6.2 years Age 59 + 11 Peak capacity stronger predictor than cigs, HTN, DM, Chol

29. The more you walk the longer you’ll live… GWTG and MORE…

30. AHA Secondary Prevention Guidelines Weight Management Goal: BMI 18.5–24.9 kg/m 2 Intervention recommendations: Calculate BMI and measure waist circumference as part of evaluation. Start weight management and physical activity as appropriate. Monitor response of BMI and waist circumference to therapy. If BMI  25 kg/m 2, goal for waist circumference is  40 inches in men,  35 inches in women. Smith SC Jr et al. Circulation 2001;104:1577-1579.

31. BMI and All-Cause Mortality Calle, NEJM 1999;341:1097

32. Blood pressure General goal: BP < 140/90 Diabetes: BP < 130/80 (ADA) Renal failure/heart failure: BP < 130/85 (JNC6) Lifestyle modification Dietary management restrict salt intake fresh fruits and vegetables AHA Secondary Prevention Guidelines 2001

33. HOT Trial Lancet 1998;351(9118):1755-62 Diastolic blood pressure Systolic blood pressure 70 75 80 85 90 95 100 105 120 130 140 150 160 170 180 190

34. Hormone replacement therapy Do not start HRT for secondary prevention AHA Secondary Prevention Guidelines 2001 Circulation 2001;104:499 www.americanheart.org

35. GWTG and MORE… L-Arginine C C H N H H H H C H H C H H N H C N H N H H CO O H

36. GWTG and MORE… L-Arginine Increases nitric oxide levels Doses 1-9 grams per day Improves endothelial function Restores ASA-induced dysfunction Antioxidant Improves renal function Improves claudication increases walking distance by 155% JACC 1998;32:1336

37. GWTG and MORE… www.srmjol.is

38. GWTG and MORE… Fish Oil www.srmjol.is Blue Whiting Capelin Herring

39. C = 8 - 24 Fatty Acids Lipids HO O Triglycerides O O O O O O Phospholipids O O O O O P G O O

40. PUFA (polyunsaturated fatty acid) Nomenclature 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Common name -  -Linoleic acid Systematic name - all cis-9,12-octadecadienoic acid Systematic name - cis-9, cis-12-octadecadienoic acid Chemist’s name - 18:2 (9Z, 12Z) (Z=cis, E=trans) Chemist’s name - 18:2  9,12 (assume cis, indicate trans) Nutritionist’s name #1 - 18:2 (n-6) Nutritionist’s name #2 - 18:2  -6 HO O 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1       

41. Fish Oil 9 patients 6 weeks 1 g/d N-3 PUFA 1 U tocopherol/d 6 weeks 5 g/d fish oil Slower VLDL and LDL oxidation Hau et al. Arterio Thromb Vasc Biol 1996;16:1197

42. Fish Oil vs Gemfibrozil Gemfibrozil 1,200 mg/d Fish oil 4g/day Stalenhoef et al Atherosclerosis 2000;153:129

43. n-3 PUFA’s and SCD Albert et al NEJM 2002;346:1113

44. GISSI-Prevenzione GISSI group, Lancet 1999;354:447

45. GWTG and MORE… Fish Oil

46. GWTG and MORE… Fish Oil

47. GWTG and MORE… Fish Oil EPA + DHA

48. Mediterranean Diet J. THOMSON "Chart of the Mediterranean Sea" Edin.18I7

49. Lyon Heart Trial De Lorgeril et al Circulation 1999;99:779 First MI Randomized Mediterranian vs Prudent 5 year trial stopped early <35% energy as fat <10% energy saturated fat <4% energy as linoleic acid >0.6% of energy as alpha-linolenic (18:3 or n-3) Eat more bread Eat more fish, less meat Eat more vegetables Must have fruit every day All butter and margarine replaced with olive oil and canola oil

50. Lyon Heart Trial De Lorgeril et al Circulation 1999;99:779 Survival with: No MI Survival with: No MI Angina CHF CVA PE Periph embol Survival with: No MI Angina CHF CVA PE Periph embol Stable angina PTCA, CABG Restenosis

51. Lyon Heart Trial De Lorgeril et al Circulation 1999;99:779 Differences in LDL-C

52. Underlying Cause

53. How often do we provide these therapies?

54. The Guidelines ABC 2 DM Cigs Exercise BMI HTN

55. …and MORE Long-term – lower ASA dose Clopidogrel benefits out to 1 year More use of warfarin in CAD More aggressive use of Beta blockers Lower LDL levels L-arginine Fish oil Mediterranean diet

56. The END