1 / 33

Coronary Revascularization in Diabetic Patients: Optimizing Outcomes in 2007

David J. Cohen, M.D., M.Sc. Director of Cardiovascular Research Saint-Luke’s Mid America Heart Institute Professor of Medicine University of Missouri-Kansas City. Coronary Revascularization in Diabetic Patients: Optimizing Outcomes in 2007.

libitha
Download Presentation

Coronary Revascularization in Diabetic Patients: Optimizing Outcomes in 2007

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. David J. Cohen, M.D., M.Sc.Director of Cardiovascular ResearchSaint-Luke’s Mid America Heart InstituteProfessor of MedicineUniversity of Missouri-Kansas City Coronary Revascularization in Diabetic Patients:Optimizing Outcomes in 2007

  2. Atherosclerosis in Diabetes Mellitus: Pathophysiologic Considerations • Abnormal platelet function •  activation and adhesion in response to shear stress •  expression of GpIIb/IIIa receptors  aggregation • More diffuse atherosclerosis pattern • Impaired coronary flow reserve reduced tolerance of embolization •  plaque burden and more lipid-rich plaques predisposed to rupture • Impaired ability to develop collaterals larger MIs • Increased response to vascular injury •  rates of restenosis and reocclusion following both balloon angioplasty and bare stent implantation

  3. Diabetes No Diabetes Ref. Diam ( per mm) 3.3% Lesion length (per 5 mm) RR=1.5 Diabetes 2.1% Current Smoker P=0.012 Prior MI 0 1 2 Impact of Diabetes on Short- and Long-Term Outcomes of PCI Predictors of TLR (n=6186) 1-year mortality (n=6534) Cutlip DE et al. JACC 2002;40:2082-9 Bhatt et al. JACC 2000;35:922-8

  4. Adjusted RR = 2.38(95% CI 1.48-3.85) Freedom from Cardiac Death (%) No Restenosis Non-Occlusive Restenosis Occlusive Restenosis Years Relationship Between Restenosis and Mortality In Diabetic Patients • 513 diabetic pts underwent 6 month f/u angio and long-term clincal f/u • 10-yr survival • No restenosis: 24% • Non-occlusive: 35% • Occlusive: 59% • Occlusive (but not non-occlusive) restenosis associated with strong, independent risk of 10-year mortality (RR 2.4) Van Belle E et al. Circulation 001;103:1218-24

  5. Optimizing Outcomes in Diabetic PCI • Drug-eluting stents– which stent for which patient? • What is the optimal antithrombotic regimen? • Discharge care and secondary prevention • Patient selection: PCI vs. CABG

  6. Optimizing Outcomes in Diabetic PCI • Do they work in diabetic patients? • Differential effects in IDDM vs. NIDDM? • Is diabetes still a risk factor for restenosis in DES era? • Device selection • Is there a preferred DES for diabetic patients? • Insights from registries and comparative clinical trials Drug-Eluting Stents

  7. CYPHER Pooled: Diabetic Subgroup Angiographic Restenosis P<0.001 P<0.001  80%  79%

  8. Pooled TAXUS Trials (II, IV, VI) Overall Diabetic Subset: Angiographic Restenosis  80%P<0.001  87%P<0.001 (n=264) (n=263)

  9. SIRIUS – Reduced Efficacy in IDDM In-Segment Restenosis P=NS P<0.001 P<0.001

  10. CYPHER Trials-- Excluding SIRIUS In-Segment Restenosis P=0.06 P<0.001 P<0.001

  11. Optimizing Outcomes in Diabetic PCI • Do they work in diabetic patients? • Differential effects in IDDM vs. NIDDM? • Is diabetes still a risk factor for restenosis in DES era? • Device selection • Is there a preferred DES for diabetic patients? • Insights from registries and comparative clinical trials Drug-Eluting Stents

  12. ISR rx Cardiogenic Shock Ostial lesion Female Diabetes Multivessel Dz Stent length(per 10 mm) Diabetes Ref. diam(per mm) Left main stenting Bifurcation stenting LAD 0.1 1 10 0.1 1 10 Independent Predictors of TVR after DES: RESEARCH and T-SEARCH Results Angio. Restenosis (n=238) 1-year MACE (n=1084) RR = 2.6 RR = 1.6 Lemos PA et al. Circulation 2004;109:1366-70 Ong ATL, et al. JACC 2005;45:1135-41

  13. Optimizing Outcomes in Diabetic PCI • Do they work in diabetic patients? • Differential effects in IDDM vs. NIDDM? • Is diabetes still a risk factor for restenosis in DES era? • Device selection • Is there a preferred DES for diabetic patients? • Insights from registries and comparative clinical trials Drug-Eluting Stents

  14. Study Protocol Patients with Diabetes Mellitus (n = 250) TAXUS™ (n = 125) CYPHER® (n = 125) 1° EP:Late lumen loss at 6 months (in-segment analysis) 2 EP:Angiographic restenosis at 6 months  50% diameter stenosis (in-segment analysis) Target lesion revascularization at 6 months

  15. P<0.001 Angiographic Outcomes In-Segment Restenosis Late Loss (mm) P=0.03 P<0.001 In-Segment In-Stent

  16. P=NS 9-Month Clinical Outcomes P=0.16 P=NS

  17. Are the ISAR-Diabetes Findings Real?Comparison with SIRIUS and TAXUS * Results excluding SIRIUS Trial

  18. Nearly 500 diabetic lesions Are the ISAR-Diabetes Findings Real?Comparison with REALITY

  19. Summary: DES in Diabetes • Both sirolimus- and paclitaxel-eluting stents substantially reduce angiographic and clinical restenosis compared with BMS • Nonetheless, DES have not eliminated the excess risk of restenosis in diabetics c/w non-diabetics • Edge effects appear to be more severe in diabetic patients greater emphasis on stenting “normal to normal” • Head to head trials not entirely consistent 2 of 3 trials suggest a restenosis advantage with Cypher, but true magnitude of clinical benefit probably overestimated

  20. Optimizing Outcomes in Diabetic PCI • Drug-eluting stents– which stent for which patient? • What is the optimal antithrombotic regimen? • Discharge care and secondary prevention • Patient selection: PCI vs. CABG

  21. Hemostatic Derangements in Diabetes • Increased platelet adhesion and activation in response to shear stress (P-selectin, Fibrinogen binding capacity) • Up-regulation of GpIIb/IIIa receptors associated with hyperglycemia, leading to enhanced platelet aggregation • Reduced capacity for endogenous thrombolysis • Intrinsic endothelial dysfunction less tolerant of in-situ thrombosis and distal embolization

  22. Diabetic/Placebo Diabetic/Abcix Non-diabetic/placebo Non-diabetic/ABcix 4.5% P=0.03 Death (%) 2.5% Days from randomization Mortality Benefit of Abciximab in Diabetic Pts • Pooled analysis of 1-year mortality from EPIC, EPILOG, and EPISTENT databases • Among patients with diabetes (n=1420), abciximab reduced 1-year mortality by 45% (20 lives saved per 1000 pts; p=0.03) • Mortality benefits particularly striking among diabetic patients with: • IDDM (4.2% vs. 8.1%, p=0.07) • Multivessel PCI (0.9% vs. 7.7%; p=0.02) Bhatt DL et al. JaCC 2000;35:922-8

  23. Are Gp2b/3a Inhibitors Still Beneficial in the High-Dose Clopidogrel Era? 1-Year Outcomes • ISAR-SWEET Trial • 701 diabetic patients (28% IDDM, 20% diet alone) undergoing elective PCI • Excluded any recent MI or ACS, angiographic thrombus, EF<30% • All pretreated with clopidogrel 600 mg at least 2 hrs prior to PCI • Randomized to abciximab vs. placebo • Primary Endpoint: 1-year D/MI Issues with ISAR-SWEET • Enrolled only low-risk diabetic patients • Observed 1-yr D/MI 8% vs. 14% expected • Trial dramatically underpowered to detect clinically meaningful differences in ischemic complications • Does not exclude a 40% reduction in 1-yr death or MI P=NS for all comparisons Death MI Death or MI Mehilli J et al. Circulation 2004;110:3627-35

  24. N=1606 1-year mortality – subgroups Results consistent across subgroups Bivalirudin better Heparin + GPI better H+GPI Bival All patients 2.5% 1.9% Eptifibatide Abciximab 2.2% 1.7% 2.7% 2.1% Age ≤75 Age >75 1.7% 1.6% 6.9% 3.6% Male gender Female gender 2.1% 1.7% 3.5% 2.5% Diabetes No diabetes 3.9% 2.3% 1.9% 1.7% Prior MI, PCI or CABG No prior MI, PCI or CABG 2.9% 2.1% 1.8% 1.6% Unstable angina <48h Unstable angina >48h 2.1% 1.2% 3.6% 1.5% Odds ratio ±95% CI for death at 12 months

  25. Optimizing Outcomes in Diabetic PCI • Drug-eluting stents– which stent for which patient? • What is the optimal antithrombotic regimen? • Discharge care and secondary prevention • Patient selection: PCI vs. CABG

  26. Secondary Coronary Prevention in Diabetes

  27. Secondary Coronary Prevention in Diabetes

  28. Secondary Coronary Prevention in Diabetes

  29. Optimizing Outcomes in Diabetic PCI • Drug-eluting stents– which stent for which patient? • What is the optimal antithrombotic regimen? • Discharge care and secondary prevention • Patient selection: PCI vs. CABG

  30. BARI: Impact of Diabetes on Survival • BARI Subgroups • Treated diabetic pts only subgroup to show significant survival advantage with CABG • 5 year survival • CABG 81% • PTCA 65% Diabetic subgroup (p=0.006) CABG PTCA NEJM 1996;335:217-25

  31. Do Diabetics Have Increased Mortality After Multivessel Stenting? Summary: Stents do not appear to have significantly attenuated the mortality advantage of CABG in multivessel CAD * P<0.05 Yellow = Stent vs. CABG

  32. Recommendations for 2007:Which diabetic patients should undergo PCI? • Single-vessel disease • No evidence of involvement of proximal or mid-LAD (i.e., no LIMA) • Patients with 2 or 3 highly discrete lesions without evidence of diffuse atherosclerosis (I.e., “low risk”) • Patients with important contraindications to CABG • Previous CABG with patent LIMA • Advanced age

  33. If you are going to perform PCI… • Think twice (esp. in multivessel dz) • Use drug-eluting stents • Use a Gp 2b/3a inhibitor (or possibly bivalirudin + high dose clopidogrel) • Maximize secondary coronary prevention, even in the short-term • Optimal glycemic control • Aggressive lipid lowering (? LDL<80) • ACE-inhibition

More Related