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A Roussin VASCULAR PROTECTION - DIABETES - 2006 è Evidence è Guidelines CDA 2003 CDA 2003 ADA 2006 ADA 2006 CHEP 2006 CHEP 2006 è Evidence è Guidelines.

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Présentation au sujet: "A Roussin VASCULAR PROTECTION - DIABETES - 2006 è Evidence è Guidelines CDA 2003 CDA 2003 ADA 2006 ADA 2006 CHEP 2006 CHEP 2006 è Evidence è Guidelines."— Transcription de la présentation:

1 A Roussin VASCULAR PROTECTION - DIABETES è Evidence è Guidelines CDA 2003 CDA 2003 ADA 2006 ADA 2006 CHEP 2006 CHEP 2006 è Evidence è Guidelines CDA 2003 CDA 2003 ADA 2006 ADA 2006 CHEP 2006 CHEP 2006 André Roussin MD, FRCP Vascular laboratory Notre-Dame Hospital (CHUM) Associate professor University of Montreal

2 A Roussin Speaker and/or Advisory board member u AstraZeneca u Bristol-Myers Squibb u Merck Frost Schering u Pfizer Canada Inc. u sanofi aventis Disclosures André Roussin MD

3 A Roussin Vascular Protection Attendee Objectives TO BE ABLE TO: u Define vascular protection and interventions u Understand the evidence u Apply CDA, ADA, CHEP and Lipid guidelines

4 A Roussin Vascular Protection Definition u Prevent the triple end-point è Stroke (mainly ischemic) è MI è Vascular death u Prevent the broader vascular end-point è Same as above + hospitalisation for ischemic events u Also è All CAD, PAD, ASO renal disease

5 A Roussin Vascular Protection Main Intervention targets u For almost all: ACE inhibitors and antiplatelet therapy u Blood pressure control u Glycemic control u Lipid control è LDL and CT/HDL è HDL, TG, ApoA/ApoB, Lp(a) u Smoking cessation u Lifestyle modification è Weight reduction è Sedentarity-activity

6 A Roussin Type II Diabetes & Coronary Heart Disease 7 Year Incidence of Fatal/Nonfatal MI from the East West Study p<0.001 P<0.001 Non-diabetic n=1373Diabetic n=1059 Haffner, et al. N Engl J Med 1998;339: year incidence rate of myocardial infarction DM- diabetes mellitus MI- myocardial infarction Vascular Protection CHD and Risk factors in perspective: 1999

7 A Roussin Vascular Protection CHD and Risk factors in perspective: 2006 Howard BV et al. Diabetes Care 2006, 29: yr

8 A Roussin Vascular Protection CHD and Risk factors in perspective: 2006 Howard BV et al. Diabetes Care 2006, 29: yr

9 A Roussin Prévention primaire Avantages et risques de AAS selon le risque coronarien à 5 ans Hayden M et al. U.S. Preventive ServicesTask Force. Ann Intern Med. 2002;136:

10 A Roussin Diabète en prévention primaire Antiplaquettaires La proportion de patients diabétiques est petite dans la plupart des études en prévention primaire -PPP: 17% -HOT: 8% -PHS: 2% -BMD: 2% -TPT: 2% Hayden M et al. U.S. Preventive ServicesTask Force. Ann Intern Med. 2002;136: < 20 %

11 A Roussin Diabète en prévention primaire : Antiplaquettaires Physicians Health Study u In PHS, patients with diabetes derived greater benefit from aspirin than those without diabetes 1 è Relative risk: 0.39 vs u Risk of MI over 5 years of follow-up 2 : è Reduced by ASA from 10 % to 4% 1. Hayden M et al. U.S. Preventive ServicesTask Force. Ann Intern Med. 2002;136: PHS. N Engl J Med 1989; 321:

12 A Roussin Diabète en prévention primaire : Antiplaquettaires Antithrombotic Trialists' Collaboration 2002 BMJ 2002, vol 24: Much of the new information comes from the early treatment diabetic retinopathy study, in which 3711 people with diabetes (and, generally, no history of myocardial infarction or stroke) were allocated to receive 650 mg aspirin dailyor placebo. % odds reduction

13 A Roussin Diabète en prévention secondaire Antiplaquettaires u Pooled data from aspirin trials in secondary prevention settings 1 u and a single trial in diabetic patients with and without coronary heart disease 2 è suggest that diabetic patients benefit as much or more from aspirin as non diabetic patients. Hayden M et al. U.S. Preventive ServicesTask Force. Ann Intern Med. 2002;136: Antiplatelet Trialists Collaboration. BMJ. 1994; 308: ETDRS Investigators. JAMA. 1992; 268:

14 A Roussin Diabète type I en prévention PRIMAIRE ADA 2006 u Utiliser AAS ( mg/jr) comme stratégie de prévention primaire chez les diabétiques type 1: è Avec risque cardio-vasculaire augmenté è Incluant ceux de plus de 40 ans è Ou ceux avec des facteurs de risque additionnels: Antécédents familiaux de maladie CV Antécédents familiaux de maladie CV Hypertension Hypertension Tabagisme Tabagisme Dyslipidémie Dyslipidémie Albuminurie Albuminurie Niveau dévidence : C AAS non étudiée < 30 ans AAS à éviter < 21 ans (S. Reye)

15 A Roussin Diabète type II en prévention PRIMAIRE ADA 2006 Utiliser AAS ( mg/jr) comme stratégie de prévention primaire chez les diabétiques type 2: Utiliser AAS ( mg/jr) comme stratégie de prévention primaire chez les diabétiques type 2: Avec risque cardio-vasculaire augmenté Avec risque cardio-vasculaire augmenté Incluant ceux de plus de 40 ans Incluant ceux de plus de 40 ans Ou ceux avec des facteurs de risque additionnels: Ou ceux avec des facteurs de risque additionnels: Antécédents familiaux de maladie CV Antécédents familiaux de maladie CV Hypertension Hypertension Tabagisme Tabagisme Dyslipidémie Dyslipidémie Albuminurie Albuminurie Niveau dévidence : A

16 A Roussin Diabète en prévention SECONDAIRE ADA 2006 Utiliser AAS ( mg/jr) comme stratégie de prévention secondaire chez les diabétiques avec: Utiliser AAS ( mg/jr) comme stratégie de prévention secondaire chez les diabétiques avec: Infarctus du myocarde Infarctus du myocarde Procédure de revascularisation Procédure de revascularisation AVC ou ICT AVC ou ICT Maladie artérielle périphérique Maladie artérielle périphérique Claudication Claudication Angine Angine Niveau dévidence: A

17 A Roussin Diabète et alternatives antiplaquettaires ADA 2006 u People with: è Aspirin allergy è Bleeding tendency è Receiving anticoagulant therapy è Recent gastrointestinal bleeding è Clinically active hepatic disease Are not candidates for aspirin therapy. Are not candidates for aspirin therapy. Other anti-platelet agents may be a reasonable alternative for patients with high risk. Other anti-platelet agents may be a reasonable alternative for patients with high risk. Level of evidence : E

18 A Roussin Clopidogrel: amplified benefit over ASA In CAPRIE patients with a history of diabetes Events : MI, IS, VD, hospitalization for ischemic event / bleeding. Events prevented / 1000 pts/yr over aspirin non-diabetic All diabetics With insulin Annual event rate (%) Annual event rate (%) ASAClopidogrel 12,7 % 11,8 % 17,7 % 15,6 % 21,5 % 17,7 % p = Bhatt et al. AJC 2002 Sep 15;90(6):625-8

19 A Roussin Multiple vascular bed disease: the CAPRIE experience Clopidogrel over ASA to prevent IS, MI, VD and Hosp for IE or bleeding / year High-risk Population ASAClopidogrel Event rate % RRR (%) ARR (%) NNT Total CAPRIE population Patients with PAD NANANANA Patients with mutivascular territory involvment NANANANA Patients with a history of more than one ischemic event 36.5 / 3yr Patients with diabetes Patients with previous CABG Patients taking lipid-lowering agents

20 A Roussin Diabète et combinaison antiplaquettaires ADA 2006 Combination therapy Combination therapy using other antiplatelet agents using other antiplatelet agents such as clopidrogel in addition to aspirin such as clopidrogel in addition to aspirin should be used in patients with severe and progressive CVD should be used in patients with severe and progressive CVD Level of evidence : C

21 A Roussin Primary efficacy end point in perspective CHARISMA vs CAPRIE Primary end point: u MI u Stroke u CV death 28 months ASA ASA + Clop. RRR P value 12 months ASA ASA + Clop. ARR Per year Events saved/ 1000pts/y r ASA + Clop. NNT Per yr If p < 0.05 CH: ALL 7.3%6.8%7% %2.91%0.21% AT7.9%6.9%13% %2.96%0.43% RF5.5%6.6%-20% %2.83%-0.88%-4.8 CP: ALL 5.83%200 Stroke7.7% MI/PAD4.8% All prev MI 6.25% PAD/Str. Prev. MI 10.7%42

22 A Roussin Lignes directrices de lACD 2003 Protection rénale et vasculaire Chez tous les patients diabétiques: Antiplaquettaire (AAS à faible dose) Antiplaquettaire (AAS à faible dose) Inhibiteur de lECA Inhibiteur de lECA Contrôle de la TA Contrôle de la TA Contrôle de la glycémie Contrôle de la glycémie Contrôle des lipides Contrôle des lipides Modification du mode de vie Modification du mode de vie Arrêt du tabagisme Arrêt du tabagisme Chez tous les patients diabétiques: Antiplaquettaire (AAS à faible dose) Antiplaquettaire (AAS à faible dose) Inhibiteur de lECA Inhibiteur de lECA Contrôle de la TA Contrôle de la TA Contrôle de la glycémie Contrôle de la glycémie Contrôle des lipides Contrôle des lipides Modification du mode de vie Modification du mode de vie Arrêt du tabagisme Arrêt du tabagisme 3. TRAITEMENT DE LA NÉPHROPATHIE 2. MAÎTRISE DE LA TA 1. PROTECTION VASCULAIRE Can J Diabetes 2003; 27:S58-S65

23 A Roussin HOPE Objectif et méthodologie de létude Critères dévaluation principaux: Mortalité CV + IM + AVC Ramipril 10 mg HS vs placebo Suivi de 4,5 ans n= ans, antécédents de maladie cardiovasculaire 55 ans, antécédents de maladie cardiovasculaire MCASMCAS AVC/ICTAVC/ICT MAPMAP Diabète + 1 autre facteur de risqueDiabète + 1 autre facteur de risque HOPE Investigators. N Engl J Med; % des pts Hypertension Hypertension Chol élevé Chol élevé HDL-Chol bas HDL-Chol bas Tabagisme Tabagisme Micro- albuminurie Micro- albuminurie Hypertension Hypertension Chol élevé Chol élevé HDL-Chol bas HDL-Chol bas Tabagisme Tabagisme Micro- albuminurie Micro- albuminurie

24 A Roussin HOPE : Ramipril à 10 mg vs placebo Bienfaits CV du ramipril chez les patients atteints de maladie CV Âge moyen: 66 ± 7 ans 5 AVC (p = 0,0003) Mortalité totale (p = 0,0053) Nouveaux cas de diabète (p = 0,0001) lM, AVC, décès dorigine CV (p = 0,000002) -22,0 Décès dorigine CV (p = 0,0002) -26,0 Infarctus du myocarde (p = 0,0005) -20,0 -16,0 -32, RRR (%) ,0 -23,0 IC (p < 0,001) HOPE Investigators. N Engl J Med; 2000.

25 A Roussin Hope Study Investigators. Lancet 2000, 355: Réduction du risque (%) IMAVC DécèsCV Néphropathiesous-jacente 22 % 33 % 37 % 24 % p = 0,027 p = 0,0001 p = 0,007 p = 0,01 HOPE : Ramipril à 10 mg vs placebo Bienfaits CV du ramipril chez les patients DIABETIQUES Rami.Plac.Epidemio TA syst TA diast patients 38% AVC Pour 38% AVC et 16% MCAS

26 A Roussin HOPE-TOO : Effets à long terme du ramipril Mortalité CV, IM et AVC Proportion de patients (paramètres dévaluation combinés) Temps (années) Étude HOPE Fin de létude HOPE p = 0,0002 N bre sous placebo N bre sous ramipril ,0 0,05 0,10 0,15 0,20 0,25 0, Ramipril Placebo HOPE/HOPE-TOO Study Investigators. Circulation. 2005; 112: % sur IECA

27 A Roussin HOPE et TA ambulatoire Comparaison avec la TA en clinique u 38 patients ±71 ans avec ASO M Inf ont eu MAPA u TA 151/81 par apport à 139/79 pour HOPE u TA en clinique 8/2 NS u MAPA jour 6/2 NS u MAPA nuit 17/8 p < u MAPA 24hr 10/4 p < 0.03 Attention! Petit sous-groupePetit sous-groupe Patients + âgésPatients + âgés Avec TA élevéeAvec TA élevée Svensson P et al. Hypertension 2001; 38: e28-e32

28 A Roussin MI and microvascular endpoints Incidence by mean systolic BP and HbA 1c concentration Adler et al. BMJ. 2000, 321: Stratton et al. BMJ. 2000, 321: MI Microvascular end points Updated mean systolic BP (mm Hg) Adjusted incidence/ 1000 person-y (%) Updated mean HbA 1c concentration (%) Adjusted incidence/ 1000 person-y (%) MI Microvascular end points UKPDS 36 UKPDS 35 MI

29 A Roussin MI and microvascular endpoints Incidence by mean systolic BP Adler et al. BMJ. 2000, 321: MI Microvascular end points Updated mean systolic BP (mm Hg) Adjusted incidence/ 1000 person-y (%) UKPDS 36 MI

30 A Roussin MI and microvascular endpoints Incidence by mean systolic BP UKPDS 36 Adler et al. BMJ. 2000, 321: Incidence rates (95% confidence interval) of myocardial infarction and microvascular end points bycategory of updated mean systolic blood pressure, adjusted for age, sex, and ethnic group expressed for white men aged yearsat diagnosis and mean duration of diabetes of 10 years MI

31 A Roussin Blood pressure control ADA 2006 u Measure BP every visit u Confirm any pressure 130/80 with 2 nd visit u If between or è Try non-pharm. Tx for max 3 months è If not controlled, add Rx u If 140/90 non-pharm. Tx AND Rx u Initial Rx to include ACEI or ARB u Add CCB, DIURETIC or BB u TARGET: BP < 130/80

32 A Roussin CHEP 2006 Treatment of Systolic-Diastolic Hypertension for Diabetes WITHOUT Diabetic Nephropathy 1. ACE-Inhibitor or ARB or 2. Thiazide diuretic or Dihydropyridine CCB IF ACE-I and ARB and DHP-CCB or Thiazide are contraindicated or not tolerated, SUBSTITUTE Cardioselective BB* or Long-acting NON DHP- CCB More than 3 drugs may be needed to reach target values for diabetic patients Urinary albumin excretion rate less than 30 mg/day * Cardioselective BB: Acebutolol, Atenolol, Bisoprolol, Metoprolol Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg Combination of first line agents Addition of one or more of: Cardioselective BB or Long-acting CCB DiabeteswithoutNephropathy DHP: dihydropyridine

33 A Roussin CHEP 2006 Treatment of Systolic-Diastolic Hypertension for Diabetes WITH Diabetic Nephropathy Urinary albumin excretion rate over 30 mg/day THRESHOLD equal or over 130/80 mmHg and TARGET below 130/80 mmHg If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired DIABETESwithNephropathy ACE Inhibitor or ARB IF ACE-I and ARB are contraindicated or not tolerated, SUBSTITUTE Long-acting CCB or Thiazide diuretic Addition of one or more of Thiazide diuretic or Long-acting CCB drugs combination may be needed

34 A Roussin CHEP 2006 Treatment of Systolic-Diastolic Hypertension for Diabetes SUMMARY More than 3 drugs may be needed to reach target values for diabetic patients If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg Diabetes withNephropathy Combination (Effective 2-drug combination) ACE Inhibitor or ARB withoutNephropathy 1. ACE-Inhibitor or ARB or 2. Thiazide diuretic or DHP- CCB

35 A Roussin Blood pressure response in the INSIGHT study Diabetic vs non-diabetic patients Brown M J et al. Hypertension 2000; 35: pts

36 A Roussin Blood pressure response in the INSIGHT study Diabetic vs non-diabetic patients Brown M J et al. Hypertension 2000; 35: pts

37 A Roussin MI and microvascular endpoints Incidence by HbA 1c concentration Stratton et al. BMJ. 2000, 321: Updated mean HbA 1c concentration (%) Adjusted incidence/ 1000 person-y (%) MI Microvascular end points UKPDS 35 MI

38 A Roussin MI and microvascular endpoints Incidence by HbA 1c concentration Stratton et al. BMJ. 2000, 321: UKPDS 35 Incidence rates and 95% confidence intervals for myocardial infarction and microvascular complications by category of updated mean haemoglobin A1c concentration, adjusted for age, sex, and ethnic group, expressed for white men aged years at diagnosis and with mean duration of diabetes of 10 years

39 A Roussin Maîtrise glycémique pour la protection vasculaire : Une fois tous les patients sous IECA, AAS et maîtrise des lipides (statine) UKPDS 35. BMJ 2000; 321: ACD 2003 : CIBLES GLYCÉMIQUES A 1c 7 % chez la plupart des patients A 1c 6 % quand cela est possible en toute sécurité Infarctus du myocarde mortel ou non : Diminution de 14 % pour chaque % de réduction de lA1C p < 0,0001 0, A moyenne mise à jour 1c Rapport de risque

40 A Roussin CCS position statement 2006 Treatment of dyslipidemia and prevention of CVD Adapté de: Can J Cardiol 2006; 22 (11): Niveau de risque Risque MCAS en 10 ans Recommendations But du traitementObjectifaccessoire LDL-Cmmol/LCT/HDLBaisse de LDL-C Apo B Élevé 20 % 20 % ou ASO ou Diabète Cible primaire < 2.0 Cible secondaire < 4.0 > 50% < 0.85 Modéré % Traiter si Traiter si > 40% < 1.05 Bas < 10% Traiter si Traiter si < 1.2

41 A Roussin Étude HPS Notion de patient à risque plutôt que de lipides anormaux Hypertension n=8,455 (41%) Hypertension CVD n=3,280 (16%) CVD PVD n=6,748 (33%) PVD Diabetes n=5,963 (29%) Diabetes CHD n=13,379 (65%) CHD with CHD 1,458 (7%) with CHD 1,458 (7%) no CHD 1,822 (9%) no CHD 1,822 (9%) with CHD 4,042 (20%) with CHD 4,042 (20%) no CHD 2,706 (13%) no CHD 2,706 (13%) with CHD 1,978 (10%) with CHD 1,978 (10%) no CHD 3,985 (19%) no CHD 3,985 (19%) no CHD 2,860 (14%) no CHD 2,860 (14%) with CHD 5,595 (27%) with CHD 5,595 (27%) with MI 8,510 (41%) with MI 8,510 (41%) no MI 4,869 (24%) no MI 4,869 (24%) 20,536patients20,536patients Lancet 2002; 360: 7-22

42 A Roussin Baseline feature Previous MI 1,007 1,255 Other CHD (not MI) No prior CHD CVDCVD PVDPVD DiabetesDiabetes ALL PATIENTS 2,042 2,606 (19.9%)(19.9%)(25.4%)(25.4%) 24% SE 2.6 reduction (2P< )(2P< ) Risk ratio and 95% CI Statin(n=10,269)Statin(n=10,269) Placebo (n=10,267) (n=10,267) Statin better Statin worse Lancet 2002; 360: 7-22 Étude HPS Évènements selon le critère dentrée

43 A Roussin 6 week pre-randomisation placebo run in phase then visits at month 1, 3, 6 and 6 monthly Atorvastatin 10mg Placebo 2838 patients CARDS Collaborative Atorvastatin Diabetes Study Objective and Design Placebo u Test the effectiveness and safety of lipid lowering for primary prevention in diabetic patients with low levels of LDL-C Colhoun H M. Lancet 2004: 364:

44 A Roussin CARDS Eligibility Criteria u Type 2 male or female diabetes years of age u No clinical history of CAD, CVD or severe PAD u LDL-C 4.14 mmol/L u TG 6.78 mmol/L u One of : è Hypertension defined as receiving antihypertensive treatment or SBP 140 mm Hg or DBP 90 mm Hg è Retinopathy è Microalbuminuria or macroalbuminuria è Current smoking Colhoun H M. Lancet 2004: 364:

45 A Roussin CARDS Endpoints u Primary Efficacy Parameters Acute CHD death Acute CHD death Non-fatal MI including silent MI Non-fatal MI including silent MI Hospitalised unstable angina Hospitalised unstable angina Resuscitated cardiac arrest Resuscitated cardiac arrest Coronary revascularisation Coronary revascularisation Stroke Stroke u Secondary Efficacy Parameters Total mortality Total mortality Any cardiovascular endpoint Any cardiovascular endpoint Lipid and lipoproteins Lipid and lipoproteins Major coronary events Colhoun H M. Lancet 2004: 364:

46 A Roussin CARDS Diabetes Related Characteristics 214 (15.0%) 228 (16.2%) Diet only Diet only 932 (65.3%) 916 (65.0%) Oral hypoglycaemic only Oral hypoglycaemic only 210 (14.7%) 207 (14.7%) Insulin only Insulin only 72 (5.0%) 59 (4.2%) Insulin+oral hypoglycaemic Insulin+oral hypoglycaemic 10.0 (3.3) 9.8 (3.2) Plasma glucose mmol/L 7.9 (1.4) 7.8 (1.4) HbA 1c % Diabetes treatment 7.9 (6.4) 7.8 (6.3) Diabetes duration (years) Atorvastatin Mean (SD) or N (%) Placebo Mean (SD) or N (%) Colhoun H M. Lancet 2004: 364:

47 A Roussin CARDS Lipid Levels by Treatment Total cholesterol (mmol/L)LDL cholesterol (mmol/L) Years of Study PlaceboAtorvastatin Average difference 26% 1.4 mmol/L (54mg/dL) p< Average difference 40% 1.2 mmol/L (46mg/dL) p< Colhoun H M. Lancet 2004: 364:

48 A Roussin CARDS Cumulative Hazard for Primary Endpoint Relative Risk Reduction 37% (95% CI: 17-52) p=0.001 Years Atorva Placebo Placebo 127 events Atorvastatin 83 events Cumulative Hazard (%) Colhoun H M. Lancet 2004: 364:

49 A Roussin CARDS Cumulative Hazard for Any CVD Endpoint Relative Risk Reduction= 32% (95% CI 15-45) p=0.001 Years Atorva Placebo Placebo 189 events Atorvastatin 134 events Cumulative Hazard (%) Colhoun H M. Lancet 2004: 364:

50 A Roussin CARDS Cumulative Hazard for All Cause Mortality Relative Risk Reduction 27% (95%CI: -1-48) p=0.059 Cumulative Hazard (%) Years Atorva Placebo Placebo 82 deaths Atorvastatin 61 deaths Colhoun H M. Lancet 2004: 364:

51 Subgroup*Placebo**Atorva** Hazard Ratio Risk Reduction (CI) LDL-C (9.5) 44 (6.1) 38% (9-58) LDL-C < (8.5) 39 (5.6) 37% (6-58) p=0.96 HDL-C (8.4) 36 (5.2) 41% (11-61) HDL-C < (9.6) 47 (6.4) 35% (5-55) p=0.71 Trig (9.6) 40 (5.5) 44% (18-62) Trig. < (8.4) 43 (6.1) 29% (-5-52) p=0.40 * units in mmol/L (mg/dL) ** N (% of randomised) CARDS Treatment Effect on the Primary Endpoint by Subgroup Favours Atorvastatin Favours Placebo Colhoun H M. Lancet 2004: 364:

52 A Roussin ASPEN Atorvastatin Study for Prevention of CAD Endpoints in Non-insulin-dependent DM Objective and Design u assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets. u 2410 pts double blind 4 year study u Composite primary endpoint: è CV death, MI, Stroke, PTCA, CABG, Resc. card. Arrest, ACS requiring hosp. Knopp RH et al. Diabetes Care 2006; 29(7):

53 A Roussin ASPEN Results for 2410 patients for 4 years Knopp RH et al. Diabetes Care 2006; 29(7): LDL-Chol and End points Atorvastatine 10 mg Placebo Reduction LDL-Chol 29% vs Placebo P < Composite Primary end-point (CPEP) All patients 13.7% HR 0.9 ns 15.0% CPEP without MI-PTCA-CABG 1905 pts 10.4% HR 0.97 ns 10.8% CPEP with MI-PTCA-CABG 505 pts 26.2% HR 0.82 ns 30.8% MI, fatal or not All patients 27% RRR P = 0.10

54 A Roussin LDL cholesterol level Atorvastatin 10 mg (n=753) Atorvastatin 80 mg (n=748) Mean baseline LDL cholesterol levels (mmol/L) after 8-week open-label treatment Final LDL cholesterol levels (mmol/L) after randomization TNT diabetes analysis Baseline and final LDL cholesterol levels Shepherd J. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA.

55 A Roussin Shepherd J. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA. Outcome Atorvastatin 10 mg (n=753) Atorvastatin 80 mg (n=748) Hazard ratio (95% CI) p Total major cardiovascular events 17.9 % 13.8 % 0.75( )0.026 Total major cerebrovascular events 10.0 % 7.0 % 0.69( )0.037 TNT diabetes analysis Efficacy outcomes

56 A Roussin Effects of long-term fenofibrate therapy on CV events Lancet :

57 A Roussin Effects of long-term fenofibrate therapy on CV events Lancet :

58 A Roussin Effects of long-term fenofibrate therapy on CV events Lancet :

59 A Roussin Effects of long-term fenofibrate therapy on CV events Lancet :

60 A Roussin Effects of long-term fenofibrate therapy on CV events Drop-outs and Drop-ins (mostly statins) Lancet :

61 A Roussin Lipid Tx: meta-analysis BMJ 2006 Major coronary events in Primary prevention trials Costa J et al. BMJ 2006; 332: Mean F-up Mean F-up 4.5 yrs 21% RRR

62 A Roussin Lipid Tx: meta-analysis BMJ 2006 Major coronary events in Secondary prevention trials Costa J et al. BMJ 2006; 332: % RRR Mean F-up Mean F-up 4.5 yrs

63 A Roussin Tabagisme: outils thérapeutiques u Le médecin u Cliniques anti-tabac u Substituts tabagiques: timbres etc u Bloqueurs non-sélectifs è Bupropion u Bloqueurs cannabinoides CB1 è Rimonabant u Bloqueurs nicotiniques Cytisine: Selective α4 β2 Nicotinic Receptor Partial Agonist Cytisine: Selective α4 β2 Nicotinic Receptor Partial Agonist Varenicline: Selective α4 β2 Nicotinic Receptor Partial Agonist Varenicline: Selective α4 β2 Nicotinic Receptor Partial Agonist

64 A Roussin Varenicline vs Bupropion vs Placebo Nides M et al. Arch Intern Med. 2006;166: Carbon monoxide confirmed continuous quit rates 10 minutes of standardized, individual smoking cessation counseling from trained staff smoking cessation booklet at the baseline visit. 7 week Tx 52 week follow-up

65 A Roussin Lifestyle Modification Low Cardiorespiratory Fitness and Physical Inactivity as Predictors of Mortality in Men with Type 2 Diabetes FIT UNFIT Wein M et al. Ann Intern Med 2000; 132:

66 A Roussin Lifestyle Modification Low Cardiorespiratory Fitness and Physical Inactivity as Predictors of Mortality in Men with Type 2 Diabetes Wein M et al. Ann Intern Med 2000; 132:

67 A Roussin Lifestyle modification CDA 2003

68 A Roussin Lifestyle modification: Aerobic physical activity ADA 2006 To improve glycemic control, assist with weight maintenance, and reduce risk of CVD, at least 150 min/week of moderate-intensity aerobic physical activity (50–70% of maximum heart rate) is recommended at least 150 min/week of moderate-intensity aerobic physical activity (50–70% of maximum heart rate) is recommended and/or at least 90 min/week of vigorous aerobic exercise (>70% of maximum heart rate) and/or at least 90 min/week of vigorous aerobic exercise (>70% of maximum heart rate) The physical activity should be distributed over at least 3 days/week and with no more than 2 consecutive days without physical activity The physical activity should be distributed over at least 3 days/week and with no more than 2 consecutive days without physical activity Level of evidence : A

69 A Roussin Lifestyle modification: Resistance exercise ADA 2006 In the absence of contraindications, people with type 2 diabetes should be encouraged to: u perform resistance exercise three times a week u targeting all major muscle groups u progressing to three sets of 8-10 repetitions u at a weight that cannot be lifted more than 8-10 times Level of evidence : A

70 A Roussin VASCULAR PROTECTION - DIABETES u For almost all: ACEI + ASA 80mg u BP < 130/80 u A1C 7% for most patients è A1C 6% if can be achieved securely u Statins for most pts with high CV risk è Reduce LDL-Chol 50% è Minimal target: LDL-Chol 2.0 mmol/L and TC/HDL 4 u Smoking cessation u Lifestyle modification è Good eating habits and healthy weight è Aerobic and resistance exercise 3 times per week


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