Adults With Diagnosed Diabetes - marmur and Diabetes for web 2006.pdf · Adults With Diagnosed...
Transcript of Adults With Diagnosed Diabetes - marmur and Diabetes for web 2006.pdf · Adults With Diagnosed...
Adults With Diagnosed Diabetes
19901990
No dataavailable
Less than 4% 4%-6% Above
6%
Mokdad AH, et al. Diabetes Care. 2000;23(9):1278-1283.
Adults With Diagnosed Diabetes
20002000
4%-6% Above 6%
Mokdad AH, et al. JAMA. 2001;286(10):1195-1200.
Epidemiology:Epidemiology: Clinical Impact of Clinical Impact of Diabetes MellitusDiabetes Mellitus
DiabetesDiabetes
The leading cause of new cases of end stage renal
disease
A 2- to 4-fold
increase in cardio-
vascular mortality
The leading cause of new
cases of blindness in
working-aged adults
The leading cause of
nontraumaticlower
extremity amputations
Diabetes Adversely Affects SurvivalDiabetes Adversely Affects Survival
NEJM 1999;339:229-234
N=1059 diabetics and 1373 non-diabetics with and without MI followed for 7 years
Observational study
Diabetic vascular pathology and PCI
Decreased endothelial thromboresistance
Platelet hyperreactivity (diabetic thrombocytopathy)
Platelet size ↑
GP IIb/IIIa receptor number ↑
Increased platelet aggregation and adhesion
Diminished fibrinolysis
Altered response to arterial injury
Increased plasma coagulation
Levels of fibrinogen ↑
UA/NSTEMI
EarlyInvasive
EarlyConservative
PCI/ CABG
Cath/ PCI/ CABG
Medical Rx
Medical Rx
Endpoints
6 mosRandomize
-24 hrs
Chest pain
4- 48 108hrs hrs
ASA, Hep,Tirofiban
Angio
Hour0
ETT
+ischemia
BaselineTroponin
TACTICS TACTICS –– TIMI 18TIMI 18
N= 2,220 ACS patients
Death/MI/Death/MI/RehospitalizationRehospitalization for ACSfor ACS
Cannon et al NEJM 2001;344:1879-1887
N= 2220 patients with ACS
0
5
10
15
20
25
30
diabetes no diabetes
conservativeinvasive
n=613n=613p=0.028p=0.028
n=1607n=1607p=0.232p=0.232
Bypass Angioplasty Bypass Angioplasty RevascularizatonRevascularizatonInvestigationInvestigation-- BARIBARI
NHLBI-sponsored PTCA vs CABGn=1829 pts with multivesseldisease5 year follow-upn=353 treated diabetics
NEJM 1996;335:217-225
diabetics
Non-diabetics
CABG
PTCA
BARI BARI -- 5 year cardiac death rates5 year cardiac death rates
0
5
10
15
20
IMA graftingSVG onlyPTCA
2.9%
18.2%
20.6%
Circulation 1997;96:1761-1769
RestenosisRestenosis in Diabetics May be Lethalin Diabetics May be Lethal
N=604 consecutive diabetic patientssuccessfully treated with PTCA were enrolled in a follow-up program including repeated angiography at 6 months
N=604 consecutive diabetic patientssuccessfully treated with PTCA were enrolled in a follow-up program including repeated angiography at 6 months
Van Belle et al Circulation 2001;103:1218-1224
Does Does StentingStenting Help?: ARTS TrialHelp?: ARTS Trial
Multicenter (67 countries) randomized and prospective study performed from April 1997 to June 1998Multicenter (67 countries) randomized and prospective study performed from April 1997 to June 1998
1,2051,205
Stentn= 600Stent
n= 600CABG
n= 605CABG
n= 605
n= 112n= 112 n= 96n= 96
Randomized
Diabetics
Abizaid et al Circulation 2001;104: 533-538
Stent:Stent: DiabeticsDiabeticsStent:Stent: Non diabeticsNon diabetics
CABG :CABG : DiabeticsDiabeticsCABG:CABG: Non diabeticsNon diabetics
100100
6060
6565
7070
7575
8080
8585
9090
9595
00 6060 120120 180180 240240 300300 360360
Even
tEv
ent --
free
su
r viv
al (
%)
free
su
r viv
al (
%)
88.488.484.484.4
76.276.2
63.463.4
ARTS TrialARTS Trial1 Year Major Events Survival Free Curve1 Year Major Events Survival Free Curve
0
5
10
15
20
25
30
35
non-insulin-treated
insulin-treated
PCICABG
Dea
th %
N=6033 patients treated with PCI or CABG at Cleveland Clinic followed for 5 years
N=6033 patients treated with PCI or CABG at Cleveland Clinic followed for 5 years
P=0.008 P<0.0001
N=2,319 Diabetic Patients
Brener et al Circulation 2004;109
Drug Delivery PlatformDrug Delivery PlatformUnique Combination
Closed Cell Design
•Consistent & uniform coverage
Polymer
•Ensures controlled, sustained release of therapeutic levels of drug over the critical healing period
•Biocompatible & antithrombogenic
MV-stentingWith Sirolimus-eluting
And ReoPro
MV-stentingWith Sirolimus-eluting
And ReoPro
FREEDOM TrialFREEDOM TrialFREEDOM Trial
Eligibility: DM patients with MV-CAD eligible for stent or surgeryExclude: Patients with acute STEMI, cardiogenic shockEligibility: DM patients with MVEligibility: DM patients with MV--CAD eligible for stent or surgeryCAD eligible for stent or surgeryExclude:Exclude: Patients with acute STEMI, cardiogenic shockPatients with acute STEMI, cardiogenic shock
CABGWith or without CPB
CABGWith or without CPB
All concomitant Meds shown to be beneficial are encouraged, including: Plavix, ACE inhibitors, b-blockers, statins etc
All concomitant Meds shown to be beneficial are encouraged, including: Plavix, ACE inhibitors, b-blockers, statins etc
PRIMARY: 5-year mortalitySECONDARY: 12-month MACCE, 5-year Quality of Life
Randomized 1:1Randomized 1:1
Fuster V and the FREEDOM Steering CommitteeFuster V and the FREEDOM Steering Committee
Roffi et al Circulation 2001;104:2767-2771
Meta-analysis of 6458 diabetic patients, and 23,072 nondiabetic patients
PCI
Oral AntiOral Anti--platelet Agents platelet Agents –– Sites of ActionSites of Action
0.00
0.01
0.02
0.03
0.04
0.05
0.06
Cum
ulat
ive
Haz
ard
Rat
e
Clopidogrel Clopidogrel + ASA*+ ASA*
1010 2020 3030
Placebo Placebo + ASA*+ ASA*
Days of FollowDays of Follow--UpUp00
PP = 0.003= 0.003N = 12,562N = 12,562
* In addition to other standard therapies.
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
MI/Stroke/CV Death Within 30 DaysMI/Stroke/CV Death Within 30 Days
21%21%Relative RiskRelative Risk
ReductionReduction
Overall 12562 9.3 11.4
Associated MI 3283 11.3 13.7No associated MI 9279 8.6 10.6Male 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 15.3ST-segment deviation 6275 11.5 14.3
No ST-segment deviation 6287 7.0 8.6Enzymes elevated at entry 3176 10.7 13.0Enzymes not elevated at entry 9386 8.8 10.9Diabetes 2840 14.2 16.7No diabetes 9722 7.9 9.9Low risk 4187 5.1 6.7Intermediate risk 4185 6.5 9.4High risk 4184 16.3 18.0History of revascularization 2246 8.4 14.4No history of revascularization 10316 9.5 10.7Revascularization after randomization 4577 11.5 13.9No revascularization after randomization 7985 8.1 10.0
Placebo + ASA*Characteristic
No. ofPatients
Clopidogrel + ASA*
Percentage of Patients with Event
Placebo BetterClopidogrel Better
Relative Risk (95% CI)
1.21.00.80.60.4
CURE Outcomes in Various Subgroups
Major/LifeMajor/Life--Threatening Bleeds within Threatening Bleeds within 77 Days of CABG SurgeryDays of CABG Surgery
N = 456N = 454Stopped > 5 days prior to Stopped > 5 days prior to CABGCABG
0.530.834.4%5.3%Pts with Maj/LT Bleeds
0.061.539.6%6.3%Pts with Maj/LT Bleeds
N = 436N = 476Stopped Stopped << 5 days prior to 5 days prior to CABGCABG
Placebo ClopidogrelEndpoint +ASA* +ASA* P Value
(n=6303) (n=6259)
PlaceboPlacebo+ ASA*+ ASA*
ClopidogrelClopidogrel+ ASA*+ ASA*
Major Bleeding by ASA DoseMajor Bleeding by ASA Dose
<100 mg 2.6% 2.0%
100-200 mg 3.5% 2.3%
>200 mg 4.9% 4.0%
ASA DoseASA Dose
McGuire DK et al Am Heart J 2004;147:246-252
To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, data was analyzed from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials
To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, data was analyzed from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials
n=3,101
n=12,699
n=1473
n=100
McGuire DK et al Am Heart J 2004;147:246-252
InsulinInsulin--sensitizing sensitizing vsvs ––providingproviding
Cannon et al N Engl J Med 2004;350:1495-1504
N = 4,162 ACS patients Compared 40 mg of pravastatindaily (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 Intensive versus Moderate Lipid Lowering with StatinsStatins after Acute Coronary Syndromesafter Acute Coronary Syndromes
Nissen et al JAMA 2004;291:1071-1080
REVERSAL
N = 654 stable angina patients Randomized to 40 mg of pravastatin daily (standard therapy) versus 80 mg of atorvastatindaily (intensive therapy)
Diabetes and ACSDiabetes 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.