Adults With Diagnosed Diabetes 1990 No data available Less than 4% 4%-6% Above 6% Mokdad AH, et al. Diabetes Care. 2000;23(9):1278-1283.
Adults With Diagnosed Diabetes 2000 4%-6% Above 6% Mokdad AH, et al. JAMA. 2001;286(10):1195-1200.
Epidemiology: Clinical Impact of Diabetes Mellitus Diabetes A 2- to 4- fold increase in cardiovascular mortality The leading cause of new cases of end stage renal disease The leading cause of new cases of blindness in workingaged adults The leading cause of nontraumatic lower extremity amputations
Diabetes Adversely Affects Survival N=1059 diabetics and 1373 nondiabetics with and without MI followed for 7 years Observational study NEJM 1999;339:229-234
Diabetic vascular pathology and PCI Increased plasma coagulation Levels of fibrinogen Decreased endothelial thromboresistance Altered response to arterial injury Diminished fibrinolysis Platelet hyperreactivity (diabetic thrombocytopathy) Platelet size GP IIb/IIIa receptor number Increased platelet aggregation and adhesion
TACTICS TIMI 18 N= 2,220 ACS patients Early Invasive Angio PCI/ CABG Medical Rx UA/ NSTEMI ASA, Hep, Tirofiban Endpoints Baseline Troponin Early Conservative Medical Rx +ischemia ETT Chest pain -24 hrs Randomize Hour 0 Cath/ PCI/ CABG 4-48 108 hrs hrs 6 mos
Death/MI/Rehospitalization for ACS N= 2220 patients with ACS 30 25 conservative invasive 20 15 10 5 0 n=613 p=0.028 diabetes n=1607 p=0.232 no diabetes Cannon et al NEJM 2001;344:1879-1887
Bypass Angioplasty Revascularizaton Investigation- BARI NHLBIsponsored PTCA vs CABG n=1829 pts with multivessel disease 5 year follow-up n=353 treated diabetics diabetics Non-diabetics CABG PTCA NEJM 1996;335:217-225
BARI - 5 year cardiac death rates 20 18.2% 20.6% 15 10 IMA grafting SVG only PTCA 5 2.9% 0 Circulation 1997;96:1761-1769
Restenosis in Diabetics May be Lethal N=604 consecutive diabetic patients successfully treated with with PTCA were enrolled in in a follow-up program including repeated angiography at at 6 months Van Belle et al Circulation 2001;103:1218-1224
Does Stenting Help?: ARTS Trial Multicenter (67 countries) randomized and prospective study performed from April 1997 to June 1998 1,205 Stent n= 600 Randomized CABG n= 605 n= 112 Diabetics n= 96 Abizaid et al Circulation 2001;104: 533-538
ARTS Trial 1 Year Major Events Survival Free Curve Event-free survival (%) 100 95 90 85 80 75 70 65 60 0 60 120 180 240 300 360 CABG: Non diabetics Stent: Non diabetics CABG : Diabetics Stent: Diabetics 88.4 84.4 76.2 63.4
Death % 35 30 25 20 15 N=2,319 Diabetic Patients PCI CABG N=6033 patients treated with with PCI PCI or or CABG at at Cleveland Clinic followed for for 5 years 10 5 0 P=0.008 non-insulintreated P<0.0001 insulin-treated Brener et al Circulation 2004;109
Drug Delivery Platform Unique Combination Closed Cell Design Consistent & uniform coverage Polymer Ensures controlled, sustained release of therapeutic levels of drug over the critical healing period Biocompatible & antithrombogenic
FREEDOM Trial Eligibility: DM patients with MV-CAD eligible for stent or surgery Exclude: Patients with acute STEMI, cardiogenic shock Randomized 1:1 MV-stenting With Sirolimus-eluting And ReoPro CABG With or without CPB All concomitant Meds shown to be beneficial are encouraged, including: Plavix, ACE inhibitors, b-blockers, statins etc PRIMARY: 5-year mortality SECONDARY: 12-month MACCE, 5-year Quality of Life Fuster V and the FREEDOM Steering Committee
Meta-analysis of 6458 diabetic patients, and 23,072 nondiabetic patients Roffi et al Circulation 2001;104:2767-2771 PCI
Oral Anti-platelet Agents Sites of Action
MI/Stroke/CV Death Within 30 Days Cumulative Hazard Rate 0.06 0.05 0.04 0.03 0.02 0.01 0.00 * In addition to other standard therapies. 0 Placebo + ASA* Clopidogrel + ASA* 10 20 30 Days of Follow-Up The CURE Trial Investigators. N Engl J Med. 2001;345:494-502. 21% Relative Risk Reduction P = 0.003 N = 12,562
CURE Outcomes in Various Subgroups Characteristic No. of Patients Percentage of Patients with Event Clopidogr el + ASA* Placebo + ASA* Overall 12562 9.3 11.4 Associated MI 3283 11.3 13.7 No associated MI 9279 8.6 10.6 Male sex 7726 9.1 11.9 Female sex 4836 9.5 10.7 65 yr old 6354 5.4 7.6 > 65 yr old 6208 13.3 15.3 ST-segment deviation 6275 11.5 14.3 No ST-segment deviation 6287 7.0 8.6 Enzymes elevated at entry 3176 10.7 13.0 Enzymes not elevated at entry 9386 8.8 10.9 Diabetes 2840 14.2 16.7 No diabetes 9722 7.9 9.9 Low risk 4187 5.1 6.7 Intermediate risk 4185 6.5 9.4 High risk 4184 16.3 18.0 History of revascularization 2246 8.4 14.4 No history of revascularization 10316 9.5 10.7 Revascularization after randomization 4577 11.5 13.9 No revascularization after randomization 7985 8.1 10.0 0.4 0.6 0.8 1.0 1.2 Clopidogrel Placebo Better Better Relative Risk (95% CI)
Major/Life-Threatening Bleeds within 7 Days of CABG Surgery Endpoint Stopped < 5 days prior to CABG Pts with Maj/LT Bleeds Placebo Clopidogrel +ASA* +ASA* P Value (n=6303) (n=6259) N = 476 6.3% N = 436 9.6% 1.53 0.06 Stopped > 5 days prior to CABG N = 454 N = 456 Pts with Maj/LT Bleeds 5.3% 4.4% 0.83 0.53
Major Bleeding by ASA Dose ASA Dose Clopidogrel + ASA* Placebo + ASA* <100 mg 2.6% 2.0% 100-200 mg 3.5% 2.3% >200 mg 4.9% 4.0%
To To evaluate the the associations of of diabetes and and hypoglycemic strategies with with clinical clinical outcomes after after acute acute coronary syndromes, data data was was analyzed from from 15,800 15,800 patients enrolled in in the the SYMPHONY and and 2nd 2nd SYMPHONY trials trials n=3,101 n=12,699 McGuire DK et al Am Heart J 2004;147:246-252
Insulin-sensitizing sensitizing vs providing n=1473 n=100 McGuire DK et al Am Heart J 2004;147:246-252
N = 4,162 ACS patients Compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy) Primary end point: composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization and stroke Cannon et al N Engl J Med 2004;350:1495-1504
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes Cannon et al N Engl J Med 2004;350:1495-1504
REVERSAL N = 654 stable angina patients Randomized to 40 mg of pravastatin daily (standard therapy) versus 80 mg of atorvastatin daily (intensive therapy) Nissen et al JAMA 2004;291:1071-1080
Diabetes and ACS Early cath is the default mode for ACS management in all patients, particularly in diabetics (TACTICS TIMI-18). Major upgrade in the early initiation and sustained use (in patients with definite atherosclerotic disease) of clopidogrel (CURE, COMMIT, CLARITY, CHARISMA). Until the results of FREEDOM are known, we should err on the side of CABG for diabetic patients with 3 vessel disease and LV dysfunction. Statins and insulin-sensitizing drugs appear to be particularly beneficial.