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					Diabetes en Revascularisatie


Menko-Jan de Boer en Lars Rydén
Namens de Task Force on Diabetes and Cardiovascular Diseases
of the European Society of Cardiology (ESC) and the European
Association for the Study of Diabetes (EASD)




NVVC
17 April 2008
                                                               MJB04/08/1
             ESC/EASD Guidelines
Diabetes, prediabetes and cardiovascular disease




                                          MJB04/08/2
              ESC/EASD Guidelines
Diabetes, pre-diabetes and cardiovascular disease

    Trials addressing diabetes and revascularisation
                 for multivessel disease




                                                  MJB04/08/3
             ESC/EASD Guidelines
Diabetes, prediabetes and cardiovascular disease

      Revascularisation of diabetic patients with
        multivessel disease in the stent area




                                                    MJB04/08/4
         Blood glucose - a continuous risk factor
               for cardiovascular disease
    Relative Risk                                         meta-analysis
         3                                               over 12 studies

      2.5


         2


      1.5


         1
             4      6             8      10       12   (mmol/L)

                               2h post load glucose (mmol/l)
Coutinho et at. Diab Care 1999;22:659



                                                                  MJB04/08/5
The prevalence of hyperglycaemia (DM or IGH)
 estimated in patients with coronary artery
                   disease

                                               Known DM

                      32                       New DM
           31         %
                                                IGT
           %
                                               isolated IFG


           12          3%                      NGR

           %

                            Bartnik M et a. Eur Heart J 2004; 25:1880




                                                      MJB04/08/6
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization
  Bypass surgery versus PCI
  Adjunctive therapy
  Revascularization in acute coronary syndromes
  Glucose control
  Unresolved issues



                                            MJB04/08/7
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization




                                            MJB04/08/8
    Diabetes and coronary revascularization
Registry study - Duke University data base
n= 3 220 (diabetes 24%) with 2-3 VD. Interventions: 1984 - 1990



                                                  88 PCI – no diabetes
                                                  86 CABG – no diabetes
                                                  76 PCI – diabetes
                                                  74 CABG – diabetes



      0      1      2       3       4         5
                  Follow up (years)




                                        (Barness et al Circulation 1997;96:2551)

                                                                   MJB04/08/9
           Diabetes and coronary revascularization
   The BARI randomized trial comparing CABG and PCI
        Patients n = 1829; Diabetes n=353 (19%)
                     Ten year survival by diabetic state
           1.0

           0.8                                                  77 % CABG No diabetes
                                                                77% PCI   No diabetes
           0.6
Survival




                                                                58 % CABG    Diabetes
           0.4                                                  45% PCI      Diabetes
                     Diabetes
           0.2       No       PCI vs. CABG p=0.59
                     Yes      PCI vs. CABG p=0.025
            0
                 0       2       4      6      8           10
                             Follow up (years)



                                                    (The BARI investigators JACC 2007; 49:1600)



                                                                                MJB04/08/10
Diabetes and coronary revascularization
  Coronary interventions in patients with
          vs. without diabetes

   Coronary Bypass Surgery
      Higher mortality
      More frequent complications
        infections, delayed wound healing…

   Percutanous coronary angioplasty
      Higher mortality
      High restenosis rate
      Increased rate of stent thrombosis
      More frequent repeat revascularizations

                                                MJB04/08/11
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization
  By pass surgery versus PCI




                                            MJB04/08/12
             By pass surgery by diabetic state
          North American retrospective cohort study
           30 day mortality and morbidity in CABG
     No diabetes n = 105 123 Diabetes n = 31663 (28%)

                                        Diabetes
 Variable
                                        No   Yes     Adjusted OR
Mortality                               2.7    3.7   1.23 (1.15-1.32)
Morbidity                               9.1   13.9   1.38 (1.33-1.44)
   MI, Stroke, Organ failure
Infection                               5.2    7.9   1.36 (1.30-1.40)
   Pneumonia, Urinary tract, Sternal
Septicemia                              0.9    1.4
Mortality or morbidity                 10.4   15.5
(Carson et al JACC 2002; 40:202)
                                              15.5

                                                            MJB04/08/13
               PCI by diabetic state
   Subgroup analysis – pooled data (n= 10 777)
  Endpoint: death, MI or repeat revascularisation

        Clinical event (%)                                 Diabetes
        25                                                     Yes
                                                               No
        20

        15

        10

         5

         0
Trial        Abizaid   Elezi Carozza    Marso    Overall
n=              954    3554     5905      364     10777
                              (After Mak & Faxon Europ Heart J 2003; 24:1087)



                                                               MJB04/08/14
                      By pass surgery versus PCI
The BARI randomized trial comparing CABG and PCI
          Patients with diabetes (n=353)
                      Five year mortality by type of intervention
                 25                        Adjusted RR
                                          7.4        8.1
 Mortality (%)




                 15

                 10

                  5

                  0
                          CABG          CABG             PCI
                          LIMA          SVG
                                         (The Bari Investigators Circulation 1997; 96:1761)



                                                                            MJB04/08/15
                                   By pass surgery versus PCI
                        Stenting vs. CABG in multivessel disease
                              Subgroup analysis from ARTS
                 Multivessel disease n = 1 205 Diabetes n = 208 (17%)
Three year survival free from stroke, MI and revascularization
                         100                   Mortality
Eventfree survival (%)



                                    CABG                    Stented PCI
                          90        4.2%        p=0.39          7.1%                Diabetes
                                                                   CABG             No
                          80
                                                                   CABG             Yes
                          70
                                                                   Stented PCI No
                          60

                          50                                       Stented PCI Yes
                               0     240    480    720 960      1200
                                           Follow up (days)

                                                           (Serruys et al Circulation 2004; 109:1114)

                                                                                        MJB04/08/16
             By pass surgery versus PCI
   CABG and PCI in the era of drug eluting stents (Cypher)
             Patients with diabetes (n = 518)
       Matched pairs CABG (n = 86) PCI (n = 86)
                            Survival free from new interventions
Angina




                                          CABG
                                          CYPHER




                              (Ben-Gal et al. Ann Thorac Surg 2006; 82:2006)



                                                              MJB04/08/17
                     By pass surgery versus PCI
           Drug eluting stents (sirolimus)
Four years survival in patients with diabetes (n = 428)
                                              HR 2.90 (95% CI 1.38-6.10)
      Overall survival (%)                    p=0.008
                                              Bare Metal Stents
                                              96%

                                              Drug eluting stents
                                              SIROLIMUS
                                              88%




                                (Spaulding et al New Engl J Med 2007; 356:989)

                                                                   MJB04/08/18
Management of diabetes and glucose control before,
       during and after PCI and CABG




Whenever possible, patients with diabetes should be       I        C
offered at least one and often multiple arterial grafts




                                                              MJB04/08/19
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization
  By pass surgery versus PCI
  Adjunctive therapy




                                            MJB04/08/20
                Adjunctive therapy - Abciximab
Subgroup analysis of three RCT (EPIC, EPILOG, EPISTENT)
Pooled patients with (n= 1 462) vs. without diabetes (n= 5 072)

                     One year survival

                            p=0.031           Diabetes + placebo
Mortality (%)




                                              No diabetes + Placebo
                                              Diabetes + ABX
                                              No diabetes + ABX




                    Follow up (days)
                                         (Bhatt et al. JACC 2000; 35:922)



                                                           MJB04/08/21
Management of diabetes and glucose control before,
       during and after PCI and CABG




                                          MJB04/08/22
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization
  By pass surgery versus PCI
  Adjunctive therapy
  Revascularization in acute coronary syndromes




                                            MJB04/08/23
     Revascularization in acute coronary syndromes
              Early revascularization in ACS comparing
        patients with (n=155) and without diabetes (n=1 067)
                   One year event rate in FRISC II
                      OR = 0.63                                  Invasive
MI or Death (%)       p = 0.066         Death (%)                Non-invasive
30                                     30
25                                     25
20      OR = 0.72                      20                        OR = 0.69
15      p = 0.018                      15                        p = NS

10                                     10       OR = 0.52
                                                p = 0.027
5                                       5
0                                       0
        No diabetes   Diabetes                 No diabetes        Diabetes
                                  (Norhammar et al J Am Coll Card 2004; 43; 585)



                                                                  MJB04/08/24
Revascularization in acute coronary syndromes
  Early PCI vs. thrombolysis in diabetic patients with AMI
       Fibrinolysis (n = 99) or Primary PCI (n = 103)
                                 Survival free from death or reinfarction
                               100
     Cumulative survival (%)



                                80                                                  Angioplasty
                                                                                    Fibrinolysis
                                60

                                40

                                20   RR for PCI 0.29 (05% CI 0.15-0.57)
                                     p<0.001
                                0

                                                Follow up (days)
                                                                          (Hsu et al Heart 2002:88: 268)



                                                                                         MJB04/08/25
Management of diabetes and glucose control before,
       during and after PCI and CABG




                                          MJB04/08/26
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization
  By pass surgery versus PCI
  Adjunctive therapy
  Revascularization in acute coronary syndromes
  Glucose control




                                            MJB04/08/27
    Revascularization in acute coronary syndromes
    Mortality predictors in invasively managed patients with ACS
                                                                          RR
                                                                          1.5




                                                    l
                            Age
                                                                          0.5




                                            l
                   Female gender




                                              ll
                          Angina                                          0.9
                    Hypertension                                          0.7




                                                             l
                       Diabetes                                           5.4




                                                l
                        Smoking                                           0.9




                                                         l
                       Previous MI                                        3.2
                                                                          1.8

                                                    l
                   ST depression
            Troponin T >0.03 µg/L                 l                       1.2
                            3-VD                     l                    1.9
n = 1 222
Diabetes                             0.2           1              1015
No             1 067                       Relative risk (95% CI)
Yes              155
                                                  (Norhammar et al J Am Coll Card 2004; 43; 585)



                                                                                  MJB04/08/28
                           The importance of glucose control
                            Glycemia and mortality following PCI
                                         (n=1 612)
                       Glucometabolic classification via fasting glucose

                                                                       1.00
                15




                                                 Cumulative survival
                                                                                                   NFG
Mortality (%)




                10

                                                                       0.92                        IFG
                 5
                                                                                                   ADA-DM
                                                                                                   CDM
                 0                                                     0.86
                     NFG
                     NFG     IFG ADA-DM CDM                                   0   1 2 3 4 5 6
                            Glycemic category                                      Follow up (years)


                                                (Muhlestein et al. Am Heart J, 2003:146: 351)



                                                                                              MJB04/08/29
                            The importance of glucose control
Target vessel revascularization and pre-procedural glycemia
   Patients with diabetes (n=162); Follow up = 9 months
                                                P=0.02                             F-glucose
                            40                                                     HbA1c
       Revascularized (%)



                            30

                            20

                            10

                             0
 Quartile                            1         2       3               4
 B-glucose mg/dl                  <107    107-128 129-195           >195
 HbA1c %                           <6.3     6.3-7-0 7.1-8.6           >8.6
                                            (Lindsay et al. Cardiovasc Revasc Med, 2007; 8:15)



                                                                                MJB04/08/30
Management of diabetes and glucose control before,
       during and after PCI and CABG

  Diabetes and coronary revascularization
  By pass surgery versus PCI
  Adjunctive therapy
  Revascularization in acute coronary syndromes
  Glucose control
  Unresolved issues



                                            MJB04/08/31
            Unresolved issues
     On the amount and quality of presently
             available information

• Limited
• Retrospective
• Therapy not updated
• Mostly subgroup-based
• Diabetes poorly described
• Glucose lowering therapy undefined


                                              MJB04/08/32
            Unresolved issues
         On urgently needed information


• Trials dedicated to diabetic patients
   Accurately characterised patients
   Well defined concomitant therapy
   Carefully described glucose lowering drugs

• Mode of revascularization
   single vs. multivessel disease
   optimised technique

• The impact of tight glycemic control
                                                MJB04/08/33
           Unresolved issues
           Important ongoing trials
FREEDOM
 Diabetes mellitus type 2
 Randomised to CABG or PCI (+DES)
 Death, MI or repeat revascularization
 Follow up 5 years
BARI IID
 Diabetes mellitus type 2
 Revascularization or optimal medical therapy
 Glucose lowering randomised
 Follow up 6 years
CARDia
 Diabetes mellitus type 2
 CABG or PCI – modern techniques



                                                MJB04/08/34
              ESC/EASD Guidelines
Diabetes, pre-diabetes and cardiovascular disease
          Management of cardiovascular risk
             acute coronary syndromes




                                              MJB04/08/35

				
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