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Getting to Goal: ‘Practical Tricks of the trade‘ How to Achieve the ABCs Robert Gabbay MD, PhD Director Penn State Hershey Diabetes Institute Penn State College of Medicine [email protected] The ‘ABCs’ • A1C • BP < 130/80 • Cholesterol (LDL<100, if CAD <70) Evidence based interventions that reduce morbidly and mortality • • • • • • • HbA1C < 7 BP < 130/80 LDL cholesterol < 100 (or <70 if CAD) Aspirin age > 50 men, 60 women with 1 risk factor ACE -age >55 Statin use- age >40 Yearly screen for nephropathy, feet, and eye exams Current Diabetes Care in US • 71 % < 1 A1c measurements per year – 18 % A1C > 9.5 – ½ A1C > 7 • ~64% blood pressure above goal • 89 % LDL > 100 • 37 % no dilated eye exam • 45 % no yearly foot exam How Low to Go? What’s the Problem? • Not Bad Patients or Bad Doctors • It’s the System • Acute Care vs. Chronic Care –Self-management • Clinical Inertia A1C < 7 Why? How? UKPDS: Hemoglobin A1C (HbA1C) 9 8.5 8 Median HbA1C (%) 7.5 7 6.5 7.9 7.0 Conventional Intensive 6 UKPDS: Risk Reductions Any Diabetesrelated Microvascular Endpoints Endpoint 0 -5 -10 % Risk Reduction -15 -20 -25 -30 -35 -40 -45 -50 Laser Rx Cataract Albuminuria But I thought it was Bad to Lower A1C too Much • All recent studies aimed at A1C = 6.5 or lower • No evidence that A1C = 7 is bad • Data says to reduce CVD- its not so much about Glucose • It’s the Blood Pressure and Cholesterol Really really important points: 1. Aggressive control early prevents complications. 2. Because of the log-linear relationship between control and complications, absolute benefits are greatest at high HbA1c values. 3. Pushing patients with advanced disease (particularly macrovascular complications) to ‘tight’ control that they cannot achieve probably increases mortality • attention to hypoglycemia and particularly nocturnal hypoglycemia Sites of Drug Action Carbohydrate DIGESTIVE ENZYMES Glucose Sulfonlyureas Meglitinides Incretins Insulin Alpha-glucosidase Inhibitors, Incretins Excessive lipolysis Defective b-cell secretion Excess glucose production Metformin TZD Incretins Reduced glucose uptake Resistance to the action of insulin TZD, Metformin Dinneen SF. Diabet Med. 1997; 14 (Suppl 3): S19-24. How to choose? • • • • Pathophysiology – I resist or I secretion? Cost Rapid onset- avoid TZD Co-morbidities – – – – – – Renal – no metformin Liver –no TZD CHF – no TZD CAD? – avoid TZD? Weight- favor metformin, incretins Concern hypo- avoid SU Points to remember • Each oral agent lower A1C 1-2 • If A1C >9, start two agents • Follow SMBG, A1C, and Titrate!!!!! T2DM treatment strategies revisited HbA1c (%) Diagnosis Target-driven therapy* 9 8 7 STEP 4 STEP 3 STEP 2 STEP 1 Basal plus prandial Basal insulin OHA combinations OHA monotherapy Lifestyle modification Adapted from Riddle M. Endo Metab Clin NA 1997;26:659―77. Riddle M. Am J Med 2004;116:35―95. *Individualise Natural History of Type 2 Diabetes Postmeal glucose Plasma Glucose Fasting glucose 126 mg/dL Insulin resistance Relative b-Cell Function Insulin secretion 20 10 0 10 20 30 Years of Diabetes Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota. 6-6 TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE Over time, most patients will need insulin to control glucose 6-7 Correcting Fasting Hyperglycemia… Is Usually the First Task!! 300 Uncontrolled A1C ~9% PG (mg/dL) “Controlled” A1C <7% 200 A1C ~6% 100 Normal A1C 5%–6% 0800 1200 1800 0800 Time of Day …then, Tackle Postprandial Hyperglycemia if A1C still >7%! Adapted with permission from Cefalu WT. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York: Marcel Dekker; 2002:1 2003 Aventis Pharmaceuticals Inc Titrating Glargine or Detemir 2 units q 3 days until FPG < 100 Its that easy and it works! Physiologic Serum Insulin Secretion Profile 75 Breakfast Lunch Dinner 50 Plasma Insulin ( µU/mL) 25 4:00 8:00 12:00 16:00 Time 20:00 24:00 4:00 8:00 Blood Pressure <130/80 Why? How? UKPDS: Effect of Intensive BP Lowering on Risk of Micro- and Macrovascular Complications 0 MI Any Diabetesrelated Endpoint Diabetesrelated Death Retinopathy Renal Failure Stroke Vision Deterioration HF Risk Reduction (%) -10 -20 21 -30 -40 -50 P=.13 24 P=.0046 32 P=.019 34 P=.0038 42 P=.29 44 P=.013 47 P=.0036 -60 56 P=.0043 -70 Benefits of tight vs less tight BP control UKPDS (United Kingdom Prospective Diabetes Study) was a randomized, prospective trial in which 1,148 hypertensive patients with type 2 diabetes were allocated to tight (<150/<85 mm Hg, n=758) or less tight (<180/<105 mm Hg, n=390) BP control and followed for a median of 8.4 years. Microvascular endpoints included retionpathy requiring photocoagulation, vitreous hemorrhage, and fatal or nonfatal renal failure. UKPDS 36. BMJ. 2000;321:412-419. UKPDS 38. BMJ. 1998;317:703-713. Consistency Across Guidelines on BP Goal in Patients With Diabetes • JNC 7: • ADA: BP Goal Is <130/80 mm Hg • NKF: Adapted from American Diabetes Association. Diabetes Care. 2003;26(suppl 1):S33-S50; NHBPEPCC. JNC 7 Express. 2003. NIH Publication No. 03-5233; NKF. Available at: www.kidney.org/general/news/diabetic.cfm?id=64. Accessed March 9, 2004. High-Risk Hypertensive Patients Require Multiple Agents to Achieve Goal Achieved Systolic BP AASK1 (134 mm Hg) ABCD2,3 (132 mm Hg) ALLHAT4 (135 mm Hg) HOT2,5 (141 mm Hg) IDNT6 (140 mm Hg) RENAAL7 (140 mm Hg) UKPDS2,8 (144 mm Hg) 1 2 3 4 Number of BP Medications 1Wright JT et al. JAMA. 2002;288:2421-2431. 2Bakris GL. J Clin Hypertens. 1999;1:141-147. RO et al. N Engl J Med. 1998;338:645-652. 4The ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997. 5Hansson L et al. Lancet. 1998;351:1755-1762. 6Lewis EJ et al. N Engl J Med. 2001;345:851-860. 7Bakris GL et al. Arch Intern Med. 2003;163:1555-1565. 8UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713. 3Estacio Evidence Based Guidelines • • • • < 130/80 (you will report <140/90) How about LOWER??? ACCORD looked at lower (120)- no better What is the first line medication? – Who cares? ALLHAT: Cumulative Event Rates for Fatal CHD or Nonfatal MI by Treatment Cumulative Event Rate (%) 20 16 12 Chlorthalidone Amlodipine Lisinopril 8 4 0 0 1 2 3 4 5 6 6,340 3,870 3,832 2,956 1,878 1,770 7 Years to Event Number at Risk: Chlorthalidone Amlodipine Lisinopril 15,255 9,048 9,054 14,477 8,576 8,535 13,820 8,218 8,123 13,102 7,843 7,711 11,362 6,824 6,662 209 215 195 ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack) participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n=15,255); amlodipine, 2.5 to 10 mg/d (n=9,048); or lisinopril, 10 to 40 mg/d (n=9,054) for planned follow-up of approximately 4 to 8 years, mean follow-up 4.9 years. ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997. Medication Treatment Algorithm? • Start with ACE or ARB and/or HCTZ – Either one - best might be early combo since all will likely need it • Third agent based on co-morbidity – Beta blocker and/or Ca channel • Add the 4th and hopefully you’ve reached goal- if not call an expert +/- alpha blocker? Tashko and Gabbay, Integrated Blood Pressure Control (2010) Practical: What can I do on when I get back to work? • • • • Track BP Don’t miss an opportunity to escalate Shared goals Standing Orders? Cholesterol LDL control <100 If CVD <70 LDL Treat the water supply? HPS Substudy: First Major Vascular Event in Patients With Diabetes 30 22 % P<0.0001 25 Placebo 20 % 15 Simvastatin 10 5 0 0 1 2 3 4 5 6 51 58 Follow-up (years) Benefit/1,000 -1 13 34 47 HPS Collaborative Group. Lancet. 2003;361:2005-2016. ASCOT-LLA: Primary End Point Atorvastatin 10 mg Placebo 4 Number of events: 100 Number of events: 154 3 36% reduction Cumulative incidence 2 (%) 1 HR=0.64 (0.50-0.83) P=0.0005 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Follow-up (yr) Nonfatal MI (including silent MI) and fatal CHD. Sever PS et al. Lancet. 2003;361:1149-1158. Statins for DM The question is: Who do we NOT treat? Putting it All together The Chronic Care Model Community Health System Health Care Organization Resources and Policies SelfManagement Support Informed, Activated Patient Delivery System Design Productive Interactions Decision Support Clinical Info Systems Prepared, Proactive Practice Team Improved Outcomes 36 Self-management support Increase adherence • Education but most important SUPPORT • Use handouts, share goals • Combo Rx for pill burden – Who else on the team can help? – Use Diabetes Educators where available Delivery System Design • Distribute tasks amongst team – It takes a TEAM to manage a Chronic disease • Care management of high risk – Stratifying your population • Regular f/u by team • Planned Visits • Dealing with CLINICLA INERTIA The Chronic Care Model Community Health System Health Care Organization Resources and Policies SelfManagement Support Informed, Activated Patient Delivery System Design Productive Interactions Decision Support Clinical Info Systems Prepared, Proactive Practice Team Improved Outcomes 39 Decision support –Evidence based guidelines (ADA) –SHARE WITH YOUR PATIENTS 41 42 Clinical Information systems Registry!!!! Track outcomes and ID those not at goal with a plan for intensification Evidence based interventions that reduce morbidly and mortality • • • • • • • HbA1C < 7 BP < 130/80 LDL cholesterol < 100 (or <70 if CAD) Aspirin age > 50 men, 60 women with 1 risk factor ACE -age >55 Statin use- age >40 Yearly screen for nephropathy, feet, and eye exams QUESTIONS?