Clinical Seminar. Which Diabetic Patient is a Candidate for Percutaneous Coronary Intervention - European Perspective

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1 Clinical Seminar Which Diabetic Patient is a Candidate for Percutaneous Coronary Intervention - European Perspective Stephan Windecker Department of Cardiology Swiss Cardiovascular Center and Clinical Trials Unit Bern Bern University Hospital, Switzerland

2 Conflicts of Interest Lecture and Consultant Fees Abbott Astra Zeneca Biosensors Boston Scientific Cordis Edwards Lifesciences Eli Lilly Medtronic Sanofi Aventis

3 Target Lesion Revascularization Network Meta-Analysis: DES vs BMS Stettler C et al. Brit Med J 28 Diabetic Patients N=3,853 Non-Diabetic Patients N=1,947

4 Benefit of Drug-Eluting Stents in Diabetic and Non-Diabetic Patients NNT for Diabetic 4 Years NNT=5 CI 5-6 NNT=7 CI 5-8 NNT for Non-Diabetic 4 Years NNT=7 CI 7-8 NNT=1 CI 8-13 SES vs BMS PES vs BMS SES vs BMS PES vs BMS

5 Mortality in Trials With Clopidogrel for >6 Months Network Meta-Analysis of DES vs BMS Stettler C et al. Brit Med J 28 Diabetic Patients N=3,853 Non-Diabetic Patients N=1,947

6 Overall Mortality in Diabetic Patients Meta-Analysis of 3,853 Diabetic Patients Stettler C et al. Brit Med J 28 Impact of Dual Antiplatelet Therapy Duration SES vs. BMS PES vs. BMS Clopidogrel <6 months Clopidogrel >6 months HR=2.37 ( ) HR=.89 ( ) Clopidogrel >6 months HR=.97 ( ) P value for interaction =.2

7 Differential Benefit of Gp IIb/IIIa-Inhibitors in ACS Patients in Relation to Diabetes Roffi et al. Circulation 21;14: day Mortality Trial N Odds Ratio & 95% CI Placebo IIb/IIIa PURSUIT % 2.4% p =.57 PRISM %.% p =.5 PRISM-PLUS 17 p = %.% GUSTO IV 239 p = % 1.2% PARAGON A 45 p = %.% PARAGON B 284 p =.6 4.3%.7% p =.2 Pooled % 1.2% NNT = 36 IIb/IIIa Better Placebo Better

8 Triton TIMI 38 Prasugrel vs. Clopidogrel by Diabetes Status: Primary End Point Wiviott SD et al. Circulation 28;118: Primary End Point (%) Diabetes Mellitus Days No Diabetes Mellitus HR.7 ( ), P<.1 HR.86 ( ), P =.2 18 Clopidogrel Prasugrel 12.2 P interaction = Days Clopidogrel 1.6 Prasugrel 9.2

9 Triton TIMI 38 Prasugrel vs. Clopidogrel Wiviott SD et al. Circulation 28;118: Non-CABG TIMI Major Bleeding 5 Diabetes Mellitus No Diabetes Mellitus HR 1.6 ( ), P =.81 HR 1.43 ( ), P =.2 5 TIMI Major Bleeding (%) Clopidogrel 2.6 Prasugrel Clopidogrel 2.4 Prasugrel Days P Days interaction =.29

10 ESC 21 Guidelines for Revascularization Compared with BMS, DES reduce the need for repeat TVR in diabetic patients (I A).

11 Which Diabetic Patient is a Candidate for Percutaneous Coronary Intervention STEMI NSTE-ACS Chronic stable angina

12 Advances in Cardiac Care in Diabetic Patients With STEMI Sobel B et al. Coronary Artery Disease 21;21: Defibrillation Monitoring Beta-Blockade 28 Aspirin Thrombolysis 12 PCI Thienopyridines 7,5 Pre-CCU era CCU era Fibrinolysis Primary PCI

13 Diabetes and Mortality in Acute STEMI GUSTO-I Thrombolysis Trial Mortality (%) (%) % % Diabetes No Diabetes Days K-H Mak et al. JACC 1997;3:171-9

14 Acute Myocardial Infarction Thrombolysis vs. Primary PCI: Short-Term Results Keeley EC et al. Lancet 23;361: P< lives and 44 MI`s saved and 11 strokes avoided for every 1 pts treated with primary PCI instead of thrombolysis 43% Death, MI, Stroke 22% 57% P= P< Meta-Analysis -N=7739 patients -23 randomized trials -8x:streptokinase vs PTCA -15x: tpa vs PTCA 5% P< % P<.1.5 Death Reinfarction Stroke ICH 1 PCI Thrombolysis

15 Acute ST-Elevation Myocardial Infarction Primary PCI versus Thrombolysis in Diabetics Timmer JR et al. Arch Intern Med 27;167: % 15 1 Diabetic Patients 3 Days OR=.49 95% CI P=.4 NNT= % 15 1 Non-Diabetic Patients 3 Days OR=.69 95% CI P=.1 NNT= Primary PCI Thrombolysis Primary PCI Thrombolysis 19 RCTs comparing PPCI and Thrombolysis in 6,315 patients

16 Prehospital Thrombolysis vs Primary PCI in STEMI Bonnefoy E et al. Eur Heart J 25;26: Outcome in Diabetic 3 Days CAPTIM Trial 25 2 P=.9 P=.29 P=.69 P= % ,8 Death, MI or Stroke 13 5,3 5,5 7,5 2,5 Death MI Stroke Primary PCI Fibrinolysis N=57 N=46

17 Mortality in Cardiogenic Shock Complicating Acute Myocardial Infarction Shindler M et al. J Am Coll Cardiol 2;36: Hochman J et al. JAMA 26;295: Long-term Outcome Month Mortality HR=.71 ( ) 45 HR=.8 ( ) Diabetes No Diabetes Revacularization Medical Theray

18 ESC 28 Recommendations for STEMI ESC 21 Guidelines for Revascularization Reperfusion therapy is indicated in all patients with history of chest pain of <12 h and with persistent ST-elevation or new LBBB (I A). Mechanical reperfusion by means of primary PCI is the revascularization mode of choice in diabetic patients with AMI. (I-A).

19 Which Diabetic Patient is a Candidate for Percutaneous Coronary Intervention STEMI NSTE-ACS Chronic stable angina

20 Diabetes and Acute Coronary Syndromes Impact on Mortality PARAGON A PARAGON B PURSUIT GUSTO IV Diabetes Independent Predictor of Mortality HR 1.7 Diabetes, N = 5,49 No Diabetes, N = 19, Days 5.5% 3.% p <.1

21 Acute Coronary Syndromes Routine Invasive Versus Conservative Strategy Anderson et al. J Am Coll Cardiol 27;5:e1-157 Death Recurrent MI OR=.75 (.63-.9) OR=.83 ( )

22 Primary Endpoint at 6 Months (%) Invasive Conservative NSTE ACS Invasive vs. Conservative Strategy Impact of Diabetes Mellitus Norhammar A et al. JACC 24;43: Roffi et al. Eur Heart J 24;25:19-8 FRISC II TACTICS-TIMI % % No Diabetes Diabetes No Diabetes Diabetes

23 Acute Coronary Syndromes PCI vs CABG in Diabetic Patients - AWESOME Sedlis SP et al. J Am Coll Cardiol 22;4: Mortality Through 5 Years -Period patients with unstable angina and at least one high risk feature (previous CABG, MI, LVEF<35%, >7 YO, IABP) -randomized to PCI or CABG -32% diabetic patients

24 Invasive Procedures in the CRUSADE Registry Brogan GX et al. Diabetes Care 26;29:^9-14 Catheterization Procedures in Patients With NSTE ACS % ,4 No DM vs NIDDM OR=1.5 95% CI ,6 No DM vs IDDM OR=.94 95% CI ,3 No Diabetes NIDDM IDDM N=31,49 N=9,773 N=5,588

25 ESC 27 Recommendations for Diabetes An early invasive strategy is recommended for diabetic patients with NSTE-ACS (I A). Diabetic patients with NSTE-ACS should receive intravenous GP IIb/IIIa inhibitors as part of the initial medical management which should be contined through the completion of PCI (IIa-B).

26 Which Diabetic Patient is a Candidate for Percutaneous Coronary Intervention STEMI NSTE-ACS Chronic stable angina

27 Diabetes and Revascularization Results from the Euro-Heart Survey Anselmino et al. Eur J Cardiovasc Prev Rehabil 28;15: Freedom from MACE No DM, Revasc No DM, No Revasc DM, Revasc Multivariable Regression HR.61 95% CI P=.25 DM, No Revasc 3,488 patients included at 11 centers in 25 European countries

28 Impact of Revascularization on Mortality in Diabetic Patients With Multivessel Disease Soares PR et al. Circulation 26;114:I-42-4 MASS II trial: 611 patients with multivessel disease randomly assigned to medical treatment, PCI or CABG Diabetic Patients Non-Diabetic Patients 2-5 years P= years P=.5

29 Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease BARI 2D Study Group. N Engl J Med 29;36: centers -Enrollment 21 to 25 -Inclusion based on coronary angiography stenosis >5% -Exclusion: immediate revascularization required, LM disease -Randomization: medical therapy vs revascularization -Revascularization method: determined by treating physician Enrollment target of 2,8 patients not met; follow-up extended by 1.5 years

30 1 Endpoint: Death MACE: Death, MI, CVA Peri-procedural MI: PCI CK-MB >3xULN CABG CK-MB >1xULN Power: 88% to detect a 3% reduction in death (14% 9.5%) Complete follow-up 93% PCI=798 pts CABG=378 pts

31 Revascularization Procedures in BARI-2D BARI 2D Study Group. N Engl J Med 29;36: Cumulative Rate of First Revascularization Procedure

32 BARI 2D vs Euro Heart Survey-DM Mortality BARI 2 D 12% at 5 years (2.4%/year) Euro Heart Survey 7.6% at 1 year ~3x Mortality MACE (death, MI, stroke) BARI 2D 24% et 5 years (2.8%/year) Euro Heart Survey 14.5% at 1 year ~4x MACE

33 Revascularization in Multivessel CAD PCI versus CABG PCI -less invasive -shorter hospitalisation -lower risk of CVA -quality of life CABG -more complete revascularization -fewer repeat revascularizations -protection against future events Gersh et al. NEJM 25

34 Meta-Analysis: CABG versus PCI Hlatky M et al. Lancet 29;373:119-7 Impact of Diabetes on Overall Mortality % 4 HR=.7 ( ) HR=.98 ( ) Diabetics (N=1233) CABG Non-Diabetics (N=6561) PCI

35 CARDIA CABG vs PCI in Diabetic Patients Kapur A et al. J Am Coll Cardiol 21;55:432-4 Clinical Outcome at 12 Months Death, MI, Stroke Death Revascularization % P= ,5 13 % P=.97 % ,8 P< ,2 3, PCI (N=254) CABG (N=248) PCI (N=254) CABG (N=248) PCI (N=254) CABG (N=248)

36 Mortality (% ) Mortality (% ) Mortality According to SYNTAX Score Banning A et al. J Am Coll Cardiol 21;55: CABG TAXUS Stent Non-Diabetic Diabetic 2 P=.26 P=.48 P=.4 2 P=.51 P>.99 P= SYNTAX Score -22 (n=437) (n=454) 33 (n=449) -22 (n=136) (n=156) 33 (n=157)

37 Adverse Cerebral Outcomes After Coronary Artery Bypass Surgery Roach et al. N Engl J Med 1996;335: Type I neurologic deficit: stroke, TIA, coma Type II neurologic deficit: deterioration of intellect or seizures Type I (Overall: 3.1%) 8 Type II (Overall: 3.%) < >8 (years)

38 Risk of Stroke in Diabetic Patients - CABG vs PCI SYNTAX Banning JACC 21 CARDIA Kapur JACC 21 % 3 2 No Diabetes Diabetes Diabetes % P=.6 3 P=.26 2,2 2,5 2 2 % 3 P=.7 2,8 1,6 1,9 1,4 PCI (N=672) CABG (N=676) PCI (N=231) CABG (N=221) PCI (N=254) CABG (N=248)

39 Antiatherosclerosis Therapy in Diabetic Patients Beckman JA et al. JAMA 22;287:257-81

40 CABG versus PCI in Diabetic Patients Diabetes increases mortality with both CABG and PCI CABG and PCI have similar safety profile (death/mi/cav) in diabetic and non-diabetic patients with low and medium complexity (SYNTAX score<33) CABG is therapy of choice for diabetic and nondiabetic patients with SYNTAX scores 33 due to higher mortality with PCI Threshold for surgery should be lower in diabetic patients than in non-diabetic counterparts (especially in IDDM) Increased risk of stroke with CABG Cave: elderly patients (>75 YO)