Adults With Diagnosed Diabetes

Transcription

1 Adults With Diagnosed Diabetes 1990 No data available Less than 4% 4%-6% Above 6% Mokdad AH, et al. Diabetes Care. 2000;23(9):

2 Adults With Diagnosed Diabetes %-6% Above 6% Mokdad AH, et al. JAMA. 2001;286(10):

3 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

4 Diabetes Adversely Affects Survival N=1059 diabetics and 1373 nondiabetics with and without MI followed for 7 years Observational study NEJM 1999;339:

5 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

6 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 hrs hrs 6 mos

7 Death/MI/Rehospitalization for ACS N= 2220 patients with ACS conservative invasive n=613 p=0.028 diabetes n=1607 p=0.232 no diabetes Cannon et al NEJM 2001;344:

8 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:

9 BARI - 5 year cardiac death rates % 20.6% IMA grafting SVG only PTCA 5 2.9% 0 Circulation 1997;96:

10 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:

11 Does Stenting Help?: ARTS Trial Multicenter (67 countries) randomized and prospective study performed from April 1997 to June ,205 Stent n= 600 Randomized CABG n= 605 n= 112 Diabetics n= 96 Abizaid et al Circulation 2001;104:

12 ARTS Trial 1 Year Major Events Survival Free Curve Event-free survival (%) CABG: Non diabetics Stent: Non diabetics CABG : Diabetics Stent: Diabetics

13 Death % 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 P=0.008 non-insulintreated P< insulin-treated Brener et al Circulation 2004;109

14 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

15 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

16 Meta-analysis of 6458 diabetic patients, and 23,072 nondiabetic patients Roffi et al Circulation 2001;104: PCI

17 Oral Anti-platelet Agents Sites of Action

18 MI/Stroke/CV Death Within 30 Days Cumulative Hazard Rate * In addition to other standard therapies. 0 Placebo + ASA* Clopidogrel + ASA* Days of Follow-Up The CURE Trial Investigators. N Engl J Med. 2001;345: % Relative Risk Reduction P = N = 12,562

19 CURE Outcomes in Various Subgroups Characteristic No. of Patients Percentage of Patients with Event Clopidogr el + ASA* Placebo + ASA* Overall Associated MI No associated MI Male sex Female sex yr old > 65 yr old ST-segment deviation No ST-segment deviation Enzymes elevated at entry Enzymes not elevated at entry Diabetes No diabetes Low risk Intermediate risk High risk History of revascularization No history of revascularization Revascularization after randomization No revascularization after randomization Clopidogrel Placebo Better Better Relative Risk (95% CI)

20 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 = % N = % Stopped > 5 days prior to CABG N = 454 N = 456 Pts with Maj/LT Bleeds 5.3% 4.4%

21 Major Bleeding by ASA Dose ASA Dose Clopidogrel + ASA* Placebo + ASA* <100 mg 2.6% 2.0% mg 3.5% 2.3% >200 mg 4.9% 4.0%

22 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:

23 Insulin-sensitizing sensitizing vs providing n=1473 n=100 McGuire DK et al Am Heart J 2004;147:

24 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:

25 Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes Cannon et al N Engl J Med 2004;350:

26 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:

27 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.