GO! DiabetesTrain the Trainer Program
Cardiovascular Disease PreventionBlood 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? • What do others besides the ADA say? • What about resistant cases?
Diabetes and HypertensionWhy? • Volume Expansion • Increased insulin levels • Higher sympathetic activity • Increased glucose level • Increased sodium resorption with hyperglycemia • Decreased arterial compliance • Obesity
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
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.
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
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
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
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.
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
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
Clinical Trials Of Anti-Hypertensive Agents In Diabetes
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
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:
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
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
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
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
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
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
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
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
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
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
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
Questions?