Treatment to reduce cardiovascular risk: multifactorial management

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1 Treatment to reduce cardiovascular risk: multifactorial management Matteo Anselmino, MD PhD Assistant Professor San Giovanni Battista Hospital Division of Cardiology, Department of Internal Medicine University of Turin, Italy

2 Background Seven year incidence rates of mortality for myocardial infarction in nondiabetic patients without prior myocardial infarction 3.5% nondiabetic patients with prior myocardial infarction 18.8% diabetic patients without prior myocardial infarction 20.2% diabetic patients with prior myocardial infarction 45.0% Haffner et al. N Engl J Med 1998; 339: 229

3 ... can the prognosis be improved?

4 Multifactorial prevention The STENO 2 study Conventional 4 years 8 years 160 n=80 n=80 Primary endpoint Microvascular Microvascular Macrovascular Macrovascular Intensive 4 years 8 years Gaede N Engl J Med 2003

5 Multifactorial prevention The STENO 2 study Impact of intensive therapy on OR 95% CI Cardiovascular disease Nephropathy Retinopathy Autonomic neuropathy Gaede N Engl J Med 2003

6 Multifactorial prevention The STENO 2 post trial Conventional 4 years 8 years 13 y n=80 Microvascular Macrovascular Mortality 160 Primary endpoint n=80 Microvascular Macrovascular Mortality Intensive 4 years 8 years 13 y Gaede N Engl J Med 2008

7 Multifactorial prevention The STENO 2 post trial Impact of intensive therapy on OR 95%CI ARR p All-cause mortality % Cardiovascular mortality % Major cardiovascular events % <0.001 Number needed to treat for 13 years to aviod one... Death Cardiovascular death Major cardiovascular event 5 patients 8 patients 3 patients Progression to nephropathy 5 patients Gaede N Engl J Med 2008

8

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10 Euro Heart Survey on diabetes and the heart Participating countries 110 centres from 25 countries 2-12 weeks per centre February 2003 to January 2004

11 Multifactorial prevention Definitions in the Euro Heart Survey Evidence based medicine The combined use of β-blockade, RAA-inhibition, antiplatelets and statins if not contraindicated Revascularization thrombolysis, PCI or CABG during index hospitalisation

12 Distribution on evidence based medicine in the Euro Heart Survey 2063 No diabetes Data missing Diabetes Data missing % 57% 44% 56% EBM + EBM - EBM + EBM - Anselmino Eur J Cardiovasc Prev Rehab 2008

13 Impact of evidence based medicine One year mortality in EHS (Kaplan-Meier) 1,00 0,99 0,98 0,97 0,96 No DM EBM + No DM EBM - DM EBM + 0,95 p< ,94 0,93 0,92 DM EBM - 0, days

14 Distribution on revascularization Thrombolysis, PCI and CABG in the Euro Heart Survey 2063 No diabetes 1425 Diabetes % 60% 33% 67% RV + RV - RV + RV - Anselmino Eur J Cardiovasc Prev Rehab 2008

15 Impact of revascularization One year cardiovascular events in EHS (Kaplan-Meier) 1,00 0,96 0,94 0,92 0,90 0,88 0,86 0,84 0,82 0,80 p< No DM RV + No DM RV - DM RV + DM RV - days 15

16 Number need to treat (NNT) Experiences from EHS EBM RV Treatment type Diabetes NNT to avoid one event Fatal Cardiovascular Evidence Based No Medicine Yes Revascularization No Yes Anselmino Eur J Cardiovasc Prev Rehab 2008

17 ... how to improve treatment?

18 ... how to improve treatment?

19

20 antiaggregants

21 THROMBOCITOPATHY

22 ASPIRIN

23 2002 ATT S FINAL REMARKS Diabetes mellitus is associated with an increased risk of vascular events, even in the absence of diagnosed CVD. Overall, among 4961 pts with diabetes antiplatelet TX was associated with only a 7% proportional reduction in serious vascular events.. These results reinforce the value of ensuring that antiplatelet TX with mg aspirin daily is considered routinely for all such patients at high or intermediate risk of occlusive vascular events (more than about 2% a year) irrespective of whether they have already had a mayor vascular events.

24

25 Risk of cardiovascular events significantly reduced in >65 yr

26

27

28 hypertension

29 UK Prospective Diabetes Study (UKPDS) 1148 hypertensive patients with type 2 diabetes tight BP control group (<150/85), the main antihypertensive agents consisted of an ACE-i (captopril, mg/day) and a BB (atenolol, mg/day), compared to less tight BP control group (<180/105 ) UKPDS 38 BMJ 1998

30 UKPDS 38 BMJ 1998

31 The Hypertension Optimal Treatment trial 18,790 hypertensive patients, 1501 of these patients had diabetes at baseline randomization to a target diastolic BP of 90, 85 or 80 mmhg. Treatment was initiated in all patients with a calcium antagonist (felodipine, 10 mg/day), adding an ACE inhibitor or a beta-blocker, and to titrate the doses, if required Hansson Lancet 1998

32 Hansson Lancet 1998

33 The Heart Outcomes Prevention Evaluation study 9541 patients who were aged 55 years or older, and who had a history of previous cardiovascular event, or diabetes (n= 3577) plus at least one other cardiovascular risk factor randomly assigned to the ACE inhibitor ramipril, 10 mg/day, or placebo HOPE Lancet 2000

34 HOPE Lancet 2000

35 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) over 33,000 patients (36%type 2 DM) with hypertension and at least one other coronary risk factor randomly assigned to chlorthalidone, amlodipine, or lisinopril (a fourth arm of doxazosin was prematurely terminated because of heart failure) ALLHAT JAMA 2002

36 ALLHAT JAMA 2002

37 The ADVANCE trial compared the use of a fixed combination of perindopril and indapamide to placebo in over 11,000 patients with type 2 diabetes all other treatments, including BP lowering agents, were left to the discretion of treating physicians Patel A Lancet 2007

38 Patel A Lancet 2007

39 European guidelines on coronary prevention Eur Heart J 2003

40

41 Gancia Journal of Hypertension 2009

42 Gancia Journal of Hypertension 2009

43 dislipidaemia

44 Relative risk for CHD (log scale) Master Classes in Preventive Cardiology 1 M. Anselmino Lower LDL-C Reduces Risk for CHD mg/dl 30% CHD risk LDL-C (mg/dl) Grundy SM et al Circulation 2004;110:

45 Gaede N Engl J Med 2003

46 Statin effect on LDL-C Dose (mg) % reduction Atorvastat Simvastat Lovastat Pravastat Fluvastat Rosuvastat LDL-C Roberts WC. Am J Cardiol. 1997;80: Stein E et al. J Cardiovasc Pharmacol Therapeut. 1997;2:7-16 Olsson A. Cardiovasc Drug Rev 2002;20:

47

48

49 LDL-C treatment goals in DM patient with and without CVD Guidelines ESC/EASD 2007 ADA/AHA/ACC 2007 JBS 2005 NCEP ATP III 2004 DM with CVD <70 mg/dl (<1.8 mmol/l) <70 mg/dl (<1.8 mmol/l) <77 mg/dl* (<2.0 mmol/l) <70 mg/dl (<1.8 mmol/l) C-LDL Goal DM without CVD <97 mg/dl (<2.5 mmol/l) <100 mg/dl (<2.6 mmol/l) <77 mg/dl* (<2.0 mmol/l) <100 mg/dl (<2.6 mmol/l) LDL-C = low-density lipoprotein cholesterol; CVD = cardiovascular disease; ESC = European Society of Cardiology; EASD = European Association for the Study of Diabetes; ADA = American Diabetes Association; AHA = American Heart Association; ACC = American College of Cardiology; JBS2 = Second Joint British Societies; NCEP ATP III = National Cholesterol Education Program Adult Treatment Panel III *Or LDL-C reduction of 30% from baseline Rydén L, et al. Eur Heart J doi: /eurheartj/ehl261; American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4 S41; Smith SC, et al. Circulation. 2006;113: ; Buse JB, et al. Circulation. 2007;115: ; Joint British Societies 2. Heart. 2005; 91(suppl V):v1 v52; Grundy SM, et al. Circulation. 2004;110:

50 Is present practice satisfactory?

51 140/90 130/80 Master Classes in Preventive Cardiology 1 M. Anselmino Blood pressure % Guidelines Blood pressure Systolic Diastolic

52 Blood pressure in patients on therapy BB + ACE/ARB + Diur Betablockade + ACEorARB Diabetes Yes No ACE-i or ARB Betablocker % Anselmino Eur J Cardiovasc Prev Rehab 2007

53 Master Classes in Preventive Cardiology 1 M. Anselmino > Lipids DM pts with stable, known CAD (n=749) % Guidelines T-Ch LDL-Ch HDL-Ch TG

54 Take home messages Glucose abnormalities affect cardiovascular prognosis Available multifactorial management is effective and highly rewarding European GL are poorly adhered to

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