115 th Annual Convention of Indiana Osteopathic Association

1. 115th Annual Convention of Indiana Osteopathic Association Diabetes and Cardiovascular Disease Dr. Bradley Weinberg, FACC Community Hospital Network Indianapolis, Indiana May 5, 2012

3. DIABETES IS A CORONARY HEART DISEASE RISK EQUIVALENT

5. Cardiovascular disease is the major cause of morbidity and mortality in diabetics It is the largest contributor to direct and indirect cost Hypertension, Dyslipidemia and Smoking commonly coexist with Diabetes Large benefits are seen when these risk factors for Cardiovascular disease are addressed concurrently

6. PREVENTING HEART DISEASE IN DIABETES BLOOD PRESSURE CONTROL A goal SBP <130 is the guideline recommendation. I target a SBP < 140 The goal DBP is less than 80 mm Hg

7. HOT TRIAL Study design 19,000 pts with diastolic pressures of 100-115 Randomized to target diastolic of < 90 or < 85 or < 80 3,000 patients had diabetes Initial drug felodipine, then ACE-inhibitor, then beta blocker then diuretic Achieved diastolics lowered 20.3 mm vs 22.3 mm vs 24.3 mm

10. ACCORD TRIAL BLOOD PRESSURE ARM 4400 DIABETICS WITH SBP of 130-180 RANDOMIZED TO SYSTOLIC BP <120 mm Hg vs <140 mm Hg

11. ACCORD Mean SBP at each study visit

12. ACCORD Outcomes by level of BP control

13. Blood pressure treatment in Diabetes Start with an ACE-I or ARB I like to add Tenoretic. (Atenolol + Chlorthalidone) It is a 4$/mo drug and chlorthalidone has data Next I will change the ACE-I to Lotrel generic which is Amlodipine + Benazepril or an ARB- Amlodipine combination drug. Finally if indicated and K and renal function OK, I add spironolactone (a secret weapon!) Most pts are controlled on 2 or 3 pills (5 drugs!)

16. A Few Practical BP tips Use home BP monitoring DASH diet ½ hr of exercise 5 days per week Treat sleep apnea For GFR < 30 ml/min, use a loop diuretic in place of thiazides and spironolactone. I like once daily torsemide. It is twice as potent as furosemide. Monitor electrolytes and renal function.

17. Preventing Heart Disease in Diabetes Lipid Management I target an LDL < 100 mg/dl or a reduction of 30-40% below baseline. If possible, I choose a one of the two highest doses of either atorvastatin or rosuvastatin. Avoid 80 mg simvastatin daily In high risk pts a target of LDL <70 mg/dl is reasonable

18. Lipid Management in Diabetes The data supporting targeting triglycerides and HDL are thin. Triglycerides will often remain high until glycemic control is achieved. I believe fenofibrate is overused. My blood pressure and lipid approaches are colored by cost considerations and pill burden issues.

19. Smoking Cessation in Diabetes Advise all smokers to quit Chantix bid taken with meals Nicotine replacement (without Chantix) Bupropion 1-800-QUIT-NOW Freedom from Smoking classes

20. Preventing Heart Disease in Diabetes Antiplatelet Agents Aspirin should be used in those with known vascular disease. Aspirin 81 mg daily is reasonable in those with multiple additional risk factors or over age 50 in men or over age 60 in women. Clopidogrel is reasonable in similar patients who cannot take aspirin. The decision can be balanced by bleeding risks.

21. Screening for Coronary Disease in Diabetics In asymptomatic patients, routine screening for coronary artery disease IS NOT recommended as it does not improve outcomes and it adds cost (and potential risks) to care without benefit

22. Glycemic Goals in non-pregnant Adults A Cardiologist’s Perspective

24. Blood Glucose / A1C And the Relationship to Macrovascular Complications

25. A1C = Average Glucose 28.7 x A1C – 41.7 = estimated average glucose

26. Targets for Glycemic Control in Most Non-Pregnant Adults

30. Type 2 Diabetes UKPDS 1% A1C decreases Complications

31. Blood Sugar Control and Cardiovascular Disease ACCORD, ADVANCE and VADT did not show improved cardiovascular outcomes with A1C under 6.5% Other data suggest post-prandial glucose which is difficult to target may contribute to adverse cardiovascular outcomes

32. A1C and Cardiovascular Outcomes So What Now?

33. A1C and Complications Data suggest lower A1Cs earlier in the course of diabetes is beneficial Long term poor control may not benefit from stringent control later, particularly with reference to coronary heart disease. Optimal A1Cs for patients with known heart disease is unclear but < 7.5 may be adequate and even < 8.0 in older and sicker patients.

34. COURAGE STUDY 20072287 patients (1999-2004) • 70% proximal narrowing in 1 or more coronaries • Objective evidence of ischemia or typical angina with an 80%+ narrowing in one or more coronaries • Suitable for PCI (percutaneous coronary intervention) EXCLUSIONS Class IV angina LVEF < 30% Prior revascularization PCI + OMT (optimal medical therapy) vs OMT alone

35. What is Optimal Medical Therapy? • Aspirin or clopidogrel • LDL < 85, HDL >40, Triglycerides < 150 • BP < 130/85 • A1C < 7.0 • 30 minutes or more of exercise 5 + days per wk • Step II AHA diet • Smoking cessation • BMI <25 • ACE-inhibitor or ARB • Long acting metoprolol, amlodipine, and long acting nitrates titrated to angina

37. COURAGE Study Thus, unstable coronary lesions that lead to myocardial infarction are not necessarily severely stenotic, and severely stenotic lesions are not necessarily unstable. Focal management of even severely stenotic coronary lesions with PCI in our study did not reduce the rate of death and myocardial infarction, presumably because the treated stenoses were not likely to trigger an acute coronary event. Furthermore, our lower-than-projected event rate in the medical-therapy group may be explained by systemic therapy that reduced plaque vulnerability through aggressive intervention for multiple risk factors and evidence-based use of medication

38. What are the implications of the COURAGE study? • PCI added to medical therapy did not reduce the risk of death, MI or other major cardiovascular events compared to optimal medical therapy alone • In patients with stable coronary artery disease, OMT and aggressive management of multiple treatment targets without initial revascularization can be safely initiated in the majority of patients with chronic stable angina

39. COURAGE study • It is reasonable to reserve revascularization for patients with unacceptable symptoms on optimal medial therapy or judged to be at very high risk based on non-invasive testing.

40. BARI 2D StudyBypass Angioplasty Revascularization2 Diabetes Study • What is the optimal treatment for patients with diabetes and angiographically defined stable ischemic heart disease? • 2368 type II diabetics with either a positive stress test and a > 50% stenosis in a major coronary artery or a >70% stenosis and typical angina pectoris

41. BARI 2D Treatment Strategies • First a cardiologist determined whether CABG or PCI (percutaneous revascularization) would be preferred if revascularization was done. • Then 2x2 randomization was done. • Optimal medical therapy alone vs Optimal medical therapy plus revascularization • Insulin sensitization initially vs. initial insulin provision (sulfonylurea or insulin or both)

42. BARI 2D RESULTS

43. BARI 2D RESULTS

44. BARI 2D RESULTS • Prompt revascularization in patients treated with intensive medical therapy for diabetes and ischemic heart disease did not reduce the rate of death or major cardiovascular events • Insulin sensitization and insulin provision had similar event rates • Among patients for who CABG was deemed appropriate, prompt revascularization reduced the rate of major cardiovascular events compared to medical therapy • Over 5 years, 42% of patients had to cross-over to revascularization because of symptom progression.

45. Patients meeting target values at 3 yrs in BARI 2D • A1C < 7.0% 48% • LDL < 100 mg/dl 83% • BP < 130/80 71% • All 3 targets 28%

46. Diabetes and Heart Failure Diabetes increases the risk of CHF independent of coronary artery disease and hypertension The risk of CHF is 2.5 x higher in men and 5 x higher in women with diabetes. Among patients hospitalized with heart failure in the US about 42% are diabetic Independent of BMI and BP, diabetics have higher LV mass, more LVH, stiffer arteries and worse systolic function than non-diabetics.

47. Diabetes and Heart Failure Diabetics commonly have diastolic dysfunction. In diabetes increased myocardial fibrosis and collagen is seen. Autonomic neuropathy may play a role in left ventricular dysfunction with impaired vagal tone and abnormal sympathetic tone. The vascular bed may have decreased capacitance due to impaired endothelial function.

48. Diabetes and Heart Failure Diabetics with heart failure have poorer survival then non-diabetics with heart failure. Age, low LVEF and diabetes are the strongest predictors of the development of worsening heart failure among patients with coronary disease.

49. Thiazolidinediones (TZDs) and Heart Failure TZDs cause fluid retention and increase the risk of CHF They activate PPAR gamma receptors in the kidney (like aldosterone) and increase renal sodium retention. This is resistant to loop diuretics but may respond to aldosterone antagonists like spironolactone and eplerenone Weight gain and edema occur more often with concomitant TZDs and insulin therapy

50. AHA and ADA guidelines on TZD use In patients with NYHA class III or IV CHF, TZDs should not be used. If patients with risks for CHF such as Cr > 2, longstanding DM, age over 70, history of CHF, prior MI, significant valvular heart disease, LVH, hypertension, or edema or weight gain with TZDs, only low doses should be used and the patient followed carefully for heart failure. If edema or weight gain occur on TZDs, the patient should be assessed for heart failure.