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GO! Diabetes Train the Trainer Program

GO! Diabetes Train the Trainer Program. Cardiovascular Disease Prevention Blood Pressure, Dyslipidemia, Antiplatelet Therapy. Diabetes and Hypertension Key Questions. Why should we pay so much attention? What parameters? Non Drug Recommendations Which drugs and how many?

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GO! Diabetes Train the Trainer Program

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  1. GO! DiabetesTrain the Trainer Program

  2. Cardiovascular Disease PreventionBlood Pressure, Dyslipidemia, Antiplatelet Therapy

  3. Diabetes and Hypertension Key Questions • Why should we pay so much attention? • What parameters? • Non Drug Recommendations • Which drugs and how many? • What do others besides the ADA say? • What about resistant cases?

  4. Diabetes and HypertensionWhy? • Volume Expansion • Increased insulin levels • Higher sympathetic activity • Increased glucose level • Increased sodium resorption with hyperglycemia • Decreased arterial compliance • Obesity

  5. HOT Trial: Effect Of Diastolic Target On CVD Events - 4 Years 48% RiskReduction 30 24.4 18.6 20 Events/ 1000 Pt-Yrs 11.9 10.0 9.9 9.3 10 0 <90 <85 <80 <90 <85 <80 DiabeticPatients n=1,501; P=0.016 Non-DiabeticPatients n=18,790; P=NS Lancet 1998;351:1755

  6. UKPDS Blood Pressure Study:Tight vs. Less Tight Control • 1148 type 2 patients • BP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up Endpoint Risk Reduction(%) P Value Any diabetes related endpoint 24 0.0046 Diabetes related deaths 32 0.019 Heart failure 56 0.0043 Stroke 44 0.013 Myocardial infarction 21 NS Microvascular disease 37 0.0092 UKPDS. BMJ. 317: 703-713. 1998.

  7. Diabetes Treatment Goalsfor Blood Pressure • Control blood pressure • 130/80 mmHg for most patients • 125/75 mmHg for patients who have proteinuria>1 g/day and renal insufficiency • Reduce the risk of end-organ failure • Reduce the risk of cardiovascular events • Myocardial infarction • Cardiovascular death • Delay or prevent the progression to heart failure JNC 7 Report. JAMA 2003;289:2560; Bakris GL et al. Am J Kidney Dis 2000;36:646 ADA. Diabetes Care 2007;30(suppl 1):S15

  8. Initial therapy Lifestyle modification Smoking cessation Weight reduction Increase physical activity Sodium restriction Pharmacologic therapy Albuminuria - ACEI/ARB, thiazide, β-blocker, CCB Albuminuria + ACEI/ARB Multiple drugs generally required ADA Guidelines for the Treatment of Hypertension Goal of therapy BP <130/80 mmHg Diabetes Care 2007;30 (Suppl 1):S15

  9. Number of Medications to Achieve Goal BP In 5 Trials of DM and/or Renal Disease UKPDS (<150/85 mmHg) 2.7 ABCD (<75 mmHg DBP) 2.8 MDRD (<92 mmHg MAP) 3.6 HOT (<80 mmHg DBP) 3.3 AASK (<92 mmHg MAP) 3.8 0 1 2 3 4 Number Of BP Meds Bakris. J Clin Hypertens 1999;1:141

  10. UKPDS Blood Pressure Study:Tight vs. Less Tight Control • 1148 type 2 patients • BP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up Endpoint Risk Reduction(%) P Value Any diabetes related endpoint 24 0.0046 Diabetes related deaths 32 0.019 Heart failure 56 0.0043 Stroke 44 0.013 Myocardial infarction 21 NS Microvascular disease 37 0.0092 UKPDS. BMJ. 317: 703-713. 1998.

  11. NKF Recommendations On TreatmentOf Hypertension And Diabetes • Blood pressure goal: ≤130/80 mmHg • BP-lowering medications should reduce both BP + proteinuria • Lower goal has been recommended to reduce renal disease progression and incidence of ischemic heart disease • Antihypertensive drug classes shown to reduce proteinuria and cardiovascular events • ACE inhibitors • --blocker (carvedilol) • -blockers • CCBs • Diuretics Bakris GL et al. Am J Kidney Dis 2000;36:646

  12. ACC/AHA Practice GuidelinesRecommendations For Patients At High Risk For HF: Hypertensive Patients • Control of systolic and diastolic HTN in accordance with recommended guidelines • Appropriate antihypertensive regimen frequently consists of several drugs used in combination • Drugs that are useful for the treatment of both HTN and HF are preferred (e.g., diuretics, ACE inhibitors, -blockers) Hunt SA et al. J Am Coll Cardiol 2001;38:2101

  13. Clinical Trials Of Anti-Hypertensive Agents In Diabetes

  14. UKPDS: ACE Inhibitor Vs -Blocker Aggregate Clinical Endpoints Relative Risk & 95% CI RR P 0.5 1 2 Any diabetes-related endpoint 1.10 0.43 1.27 Diabetes-related deaths 0.28 1.14 All-cause mortality 0.44 1.20 Myocardial infarction 0.35 1.29 Microvascular disease 0.30 1.12 Stroke 0.74 FavorsACE Inhibitor Favors-Blocker UKPDS Group. BMJ 1998;317:713

  15. Superior Drugs? Variable Results Thiazide, ACE, CCB, BB BB = ACE ACE > CCB ACE + CCB > ACE > CCB ARB > BB ACE > ARB Thiazide > ARB Thiazide ≥ ACE Thiazide ≥ CCB ACE > Thiazide Vs Placebo UKPDS: ABCD: FACET: LIFE: CONSENSUS: ALLHAT: ALLHAT: ALLHAT: AUSTRALIAN:

  16. Which Class Of Agents Should Be Added Second-Line? • Thiazide diuretics • Complementary mechanism to ACEs or ARBs • ALLHAT showed benefit • Particularly effective in African American patients • BUT slightly higher deterioration of glucose metabolism • Beta blockers • Good evidence of benefit particularly for those with coronary heart disease or congestive heart failure • BUT mechanism of action may not complement ACEs or ARBs

  17. Treatment Algorithm - Hypertension BP >130/80 mmHg Lifestyle Intervention Smoking Cessation Quarterly to semi-annual follow-up Monthly to quarterly follow-up SBP <130 and DBP <80? Yes No Coronary Disease Albuminuria/CVD Risk Factors β-blocker Thiazide ACE/ARB Virtually all two drug combinations should include a thiazide diuretic The third drug could (should) be a calcium channel blocker In the setting of kidney disease and significant proteinuria, consider combined ACE/ARB therapy In the setting of kidney or heart disease, consider adding a furosemide bid or torsemide

  18. Additional BP Recommendations • Lower blood pressure gradually in the elderly • If unable to achieve goal, don’t hesitate to discuss with peers • Check for orthostasis in some patients when clinically indicated • If angiotensin modifying drugs or diuretics are used, monitor renal function and potassium • Use as many medicines as necessary to achieve blood pressure target • 130/80 mmHg • 125/75 mmHg if proteinuria is found • Begin with an angiotensin modifying drug • Add a thiazide in African American patients • Add a Beta blocker in patients with heart disease ADA. Diabetes Care 2007;30(Suppl1):16

  19. Causes Of Resistant Hypertension • Improper blood pressure measurement • Excess sodium intake • Inadequate diuretic therapy • Medication • Inadequate doses • Drug actions and interactions (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives) • Over-the-counter (OTC) drugs and herbal supplements • Excess alcohol intake • Identifiable causes of hypertension

  20. Lipids American Diabetes Association LDL <100 mg/dL (<70 mg/dL in patients at “highest risk”) HDL >40 mg/dL (>50 mg/dL in females) TG <150 mg/dL National Cholesterol Education Program LDL <100 mg/dL (<70 mg/dL in patients at “highest risk”) Non-HDL <130 mg/dL

  21. 4S LIPID CARE PROVE-IT HPS(estimated) WOSCOPS CARDS TNT TNT HPS(estimated) AFCAPS Statins:Primary And Secondary Prevention 25 20 % With CVD Event 15 10 5 0 50 70 90 110 130 150 170 190 210 LDL-C (mg/dL) Adapted from Illingworth. Med Clin North Am 2000;84:23 and LaRosa. N Engl J Med 2005;352 (e-pub) and Colhoun. Lancet 2004;364:685

  22. ADA Standards 2007Dyslipidemia • Fasting lipid profile annually • Without overt CVD • LDL<100 • At age 40 start on statin regardless of LDL to reduce LDL 30-40% • With overt CVD • Start statin to reduce LDL 30-40% • LDL<70 is an option • Normalizing triglycerides and raising HDL with fibrates reduces CV events

  23. ADA Standards 2007Dyslipidemia • High LDL, High triglycerides, Low HDL • Consider statin + fibric acid • Remember the increased risk of rhabdomyolysis • Consider statin + niacin • Remember niacin can increase glucose levels • moderate doses = mild changes in glycemia

  24. Statin-Fibrate Combination Therapy: Pharmacokinetic Interactions GemfibrozilFenofibrate Atorvastatin Not available Not available Pravastatin  in Cmax by 2-fold No effect Fluvastatin No effect Not available Simvastatin  Cmax by 112% No effect Cerivastatin  Cmax by 2 to 3-fold No effect Rosuvastatin  in Cmax by 2-fold No effect Cmax =peak concentration Pan W-J et al. J Clin Pharmacol 2000;40:316; Backman JT et al. Clin Pharmacol Ther 2000;68:122 Kyrklund C et al. Clin Pharmacol Ther 2001;69:340; Backman JT et al. Clin Pharmacol Ther 2002;72:685; Davidson MH. Am J Cardiol. 2002;90(suppl):50K; Prueksaritanont T et al. Drug Metab Dispos 2002;30:1280; Martin PD et al. Clin Ther 2003;25:459

  25. Statin-Fibrate Combination Therapy:Retrospective Analysis Of Adverse Events Number No. Cases No. Cases Prescriptions Reported MedicationReported1Dispensed2,3Per Million Gemfibrozil + any Statin 590 6,757,000 87.3 Gemfibrozil + Cerivastatin 533 116,000 4,590 Gemfibrozil + other Statins 57 6,641,000 8.58 Fenofibrate + any Statin 16 3,519,000 4.55 Fenofibrate + Cerivastatin 14 100,000 140 Fenofibrate + other Statins 2 3,419,000 0.58 1Adverse Event Reporting System, U.S. Food and Drug Administration 2National Prescription Audit Plus report, IMS Health 3Concomitancy Report, VERISPAN, LLC

  26. Anti-platelet TherapyADA Standards • Recommendations for Aspirin • ASA 75-162 mg/day for 2o prevention • ASA 75-162 mg/day for 1o prevention • Age > 40 • Any age with CV risk factors (htn, hyperlipidemia, renal disease, family history, smoking) • Not recommended ages < 21 (Reye’s syndrome) • Clopidogrel • Very high risk diabetics; intolerance to ASA

  27. Questions?

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