Telechargé par yassineseddik

accident vasculaire 12 nov 20111

publicité
How to manage Diabetes in the
acute vascular accident ?
Ines KHOCHTALI (Monastir, Tunisia)
INTRODUCTION
• Diabetes : Huge problem
• Under diagnosed
• Cardiovascular (CV) disease is the primary complication of diabetes;
approximately 65% of deaths in people with diabetes are due to
heart disease.
• Three-quarters are attributable to coronary artery disease and the
remainder to cerebrovascular or peripheral vascular events.
• Hyperglycemia is an independant predictor of mortality
• Each 1% increase in HbA1c poses 28% relative risk of cardiovascular
event
Lancet 2000: 355: 773-8
Cardiovascular mortality
100
80
60
Survey (%)
40
No diabetes, no MI (n=1,304)
diabetes no MI (n=890)
No diabetes with MI (n=69)
Diabetes with MI (n=169)
20
0
0
1
2
3
4
YEARS
Haffner SM et al. N Engl J Med. 1998;339:229-234.
5
6
7
8
Pathophysiology:
Diabetic coronary heart disease
•
•
•
•
•
•
Diffuse
Woman
Silent Ischemic myocardial
Other cardiovascular risk factors
High mortality
Restenosis
DIABETES AND STROKE
– Independent risk factor for ischaemic stroke
– Elevated blood glucose in the early phase of stroke
is associated with death and poor recovery
– BP in patients with diabetes should be
<130/80mmHg
Clinical Case
• Mr M, 65 year-old-man
 Diabetes since 11 years : metformin : 2000 mg/day,
glibenclamide: 10 mg/day
 Hypertension since 4 years : nifedipine : 40 mg/day
 Smoking : 10 cigarettes / day
Chest pain  ICU
Diagnosis: acute MI : ST +
Glycemia: 13 mmol/l, Hb A1c: 9%, TRP positive, creatinin:
1OO µmol/l, LDLc: 1.4 g/l, Tg: 1.1 g/l, HDL c: 0.5 g/l
What do you recommend ?
• Question n°1: glycemia goal?
•Question n°2: which treatment ?
Diabetes : prognosis factor of mortality
STEMI, ST-segment elevation myocardial infarction
UA/NSTEMI, unstable angina/ non-STEMI.
JAMA, 2007—Vol 298, No. 7
Diabetes : prognosis factor of mortality
Diabetes Metab Res Rev 2005; 21: 143–149.
Glycemic Threshold in CABG
Portland data suggest BG:
< 150 mg/dl for mortality
< 175 mg/dl for infection
< 125 mg/dl for atrial fibrillation
Furnary et al J Thorac Cardiovasc Surg 2003;123:1007-21
TREATMENT: insulin or oral anti
diabetic??
Insulin >
OAD ???
DIGAMI Study
Diabetes, Insulin Glucose Infusion in Acute Myocardial
Infarction(1997)
•
•
•
•
•
•
600 patients
Acute MI With BG > 200 mg/dl
Intensive Insulin Treatment
IV Insulin For > 24 Hours
Four Insulin Injections/Day For > 3 Months
Reduced Risk of Mortality By:
28% Over 3.4 Years
51% in Those Not Previous Diagnosed
JACC1997
Cardiovascular Risk
Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study
Standard treatment
IV Insulin 48 hours, then
All Subjects
.7
.5
.5
.4
.3
.3
.2
.2
.1
.1
0
0
1
2
3
4
Years of Follow-up
(N = 272)
Risk reduction (51%)
P = .0004
.6
.4
0
Low-risk and Not Previously on Insulin
.7
(N = 620)
Risk reduction (28%)
P = .011
.6
5
4 injections daily
0
1
2
3
4
Years of Follow-up
5
Malmberg, et al. BMJ. 1997;314:1512-1515.
6-11
DIGAMI 2
• DESIGN: DIGAMI 2 : multicentre, prospective randomized, open
trial with blinded evaluation comparing three different management
strategies in patients with type 2 diabetes and acute myocardial
infarction.
• 1253 patients , 48 centers , 2 years
• Group 1: 24 h insulin– glucose infusion followed by a subcutaneous
insulin-based longterm glucose control (n=474)
• Group 2: insulin – glucose fellowed by standard therapy (n=473)
• Group 3: routine therapy (n= 306)
 HbA1C : 7,2% in 3 groups
JACC 2002
Malmberg K, Eur Heart Journ 2005 , 26, 650
DIGAMI 2
P > .05
Effect of glucose insulin- potassium
infusion : GIK
The CREATE-ECLA Randomized Controlled Trial
Purpose: To determine the effect of high-dose GIK infusion on
mortality in patients with STEMI.
Methods : Randomized controlled trial conducted in 470 centers
worldwide among 20 201 patients with STEMI who presented
within 12 hours of symptom onset. The mean age of patients
was 58.6 years, and evidence-based therapies were commonly
used.
Main Outcome Measures Mortality, cardiac arrest, cardiogenic
shock, and reinfarction at 30 days after randomization
Conclusion: In this large, international randomized trial,
high-dose GIK infusion had a neutral effect on mortality,
cardiac arrest, and cardiogenic shock in patients with acute
STEMI.
JAMA 2005: 293(4):437-446
Intensive Insulin Therapy in Critically Ill
Patients—Morbidity and Mortality Benefits
Insulin therapy: post cardiac surgery
Percent
Reduction
Mortality
Sepsis
Dialysis
Blood
Transfusion
Polyneuropathy
0
-10
-20
-30
-40
-50
34%
46%
41%
44%
50%
-60
van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.
QUEL ANTIDIABETIQUE ORAL ?
Sulfonylureas and ischemic events
Sulfonylureas and ischemic events
Stimulus
physiologique
Pharmacologic
Action
Therapeutic
Response
Pancreatic -cell
 glucose
Close channels
Insulin secretion
Open channels
Ischemic
preconditioning
Tissu
SUR 1
myocardium
 O2
SUR 2A
Ii
t
Sulfonylureas and ischemic events
Pharmacological agents that open K-ATP
channels have a protective effect similar to that
of prior ischemia, and agents closing the
channels oppose preconditioning by ischemia.
-Glimepiride, gliclazide, glibenclamide (
glyburide)
METFORMIN
1. Reduction of excessive Hepatic Glucose Output
2. Stimulation of insulin-mediated muscle glucose
uptake -glycogen synthesis is increased
3. Weight loss
4. Increased fibrinolytic activity
5. Decreased platelet aggregability
• Contraindications: Patients with hepatic or renal
impairment, cardiac failure, patients > 75 yrs of age.
Stable period ?
• Question n°1: glycemia goal?
•Question n°2: which treatment ?
Any Diabetes Related Endpoint ( UKPDS)
1401 of 3867 patients (36%)
% of patients with an event
60%
Conventional (1138)
Intensive (2729)
p=0.029
40%
20%
Risk reduction 12%
(95% CI: 1% to 21%)
0%
0
3
6
9
12
Years from randomisation
15
N Engl J Med 2008;359:1577-89.
METAANALYSE
Differences between the ACCORD and ADVANCE studies
Characteristic
ACCORD
ADVANCE
Outcome (intensive vs standard)
•Median HbA1C at study end (%)
•Death from any cause (%)
•Death from cardiovascular cause (%)
•Nonfatal MI (%)
•Nonfatal stroke (%)
•Major/severe hypoglycemia (%/y)
•Weight gain (kg)
•Current smoking (%)
6.4 vs 7.5* 6.4 vs 7.0*
5.0 vs 4.0* 8.9 vs 9.6
2.6 vs 1.8* 4.5 vs 5.2
3.6 vs 4.6* 2.7 vs 2.8
1.3 vs 1.2
3.8 vs 3.8
3.1 vs 1.0* 0.7 vs 0.4
3.5 vs 0.4
0.0 vs -1.0*
10 vs 10
8 vs 8
N Engl J Med 2008; 358:2630-2633.
Glycemic Recommendations for Non-Pregnant
Adults with Diabetes (1)
A1C
<7.0%*
Preprandial capillary plasma
glucose
70–130 mg/dl*
(3.9–7.2 mol/l)
Peak postprandial capillary
plasma glucose†
<180 mg/dl*
(<10.0 mmol/l)
ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.
ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S21. Table 10.
Recommendations:
Glycemic Goals in Adults (3)
• Conversely, less stringent A1C goals may be
appropriate for patients with
–History of severe hypoglycemia, limited life
expectancy, advanced microvascular or
macrovascular complications, extensive comorbid
conditions
– Those with longstanding diabetes in whom the general
goal is difficult to attain despite diabetes selfmanagement education, appropriate glucose
monitoring, and effective doses of multiple glucose
lowering agents including insulin (C)
ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.
ADA recommendations
ADA JANV 2010
Avoid TZD treatment
In patients with symptomatic heart
failure (C)
Metformin use in patients with stable CHF
Indicated if renal function is normal
Should be avoided in unstable or
hospitalized patients with CHF (C)
Effets du GLP-1
POST PRANDIAL GLYCEMIA AND
CVD
• Acarbose:
CVD: - 49 %
STOP-NIDDM Trial demonstrated that,
in subjects with IGT, acarbose
treatment was effective in reducing the
risk of type 2 diabetes.
• It also suggested that it was associated
with a reduction in hypertension and
cardiovascular disease (HR 0,62 p<
0,004). JAMA 2003
Recommendations: Hypertension/Blood Pressure
Control
Goals
• A goal systolic blood pressure <130 mmHg is
appropriate for most patients with diabetes (C)
• Based on patient characteristics and response to
therapy, higher or lower systolic blood pressure
targets may be appropriate (B)
• Patients with diabetes should be treated to a
diastolic blood pressure <80 mmHg (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood Pressure
Control
• Pharmacologic therapy for patients with diabetes and
hypertension
– Pair with a regimen that includes either an ACE
inhibitor or angiotensin II receptor blocker
– to achieve blood pressure targets
– Thiazide diuretic should be added to those with
estimated GFR ≥30 ml x min/1.73 m2
– calcium channel blockers
– Beta-blockers If past ACS
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations:
Dyslipidemia/Lipid Management
Screening
• In adults with low-risk lipid values
• LDL cholesterol <100 mg/dl
• HDL cholesterol >50 mg/dl
• Triglycerides <150 mg/dl)
• In individuals with overt CVD
– Lower LDL cholesterol goal of <70 mg/dl
(1.8 mmol/l), using a high dose of a statin, (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S29.
Statins: Reduction in 10-Year Risk of Major CVD* in
Patients with Diabetes
Secondary Prevention
Relative risk
reduction
Absolute risk
reduction
LDL
cholesterol
reduction,
mg/dl (%)
Statin dose and
comparator
Risk
reduction
4S-DM1
Simvastatin 20-40 mg vs.
placebo
85.7 to 43.2%
50%
42.5%
186 to 119
(36%)
ASPEN2
Atorvastatin 10 mg vs.
placebo
39.5 to 24.5%
34%
12.7%
112 to 79
(29%)
Simvastatin 40 mg vs.
placebo
43.8 to 36.3%
17%
7.5%
123 to 84
(31%)
Pravastatin 40 mg vs.
placebo
40.8 to 35.4%
13%
5.4%
136 to 99
(27%)
Atorvastatin 80 mg vs. 10
mg
26.3 to 21.6%
18%
4.7%
99 to 77 (22%)
Studyref.
HPS-DM3
CARE-DM4
TNT-DM5
*Endpoints=CHD death, nonfatal MI
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S30. Table 11.
Recommendations:
Antiplatelet Agents (3)
• Use aspirin therapy (75–162 mg/day)
– Secondary prevention strategy in those with diabetes with a
history of CVD (A)
• For patients with CVD, documented aspirin allergy
– Clopidogrel (75 mg/day) should be used (B)
• Combination therapy with ASA (75–162 mg/day) and
clopidogrel (75 mg/day)
– Reasonable for up to a year after an acute coronary syndrome
(B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31.
Recommendations:
Coronary Heart Disease Treatment (1)
• To reduce risk of cardiovascular events in patients
with known CVD, use
– ACE inhibitor* (C)
– Aspirin* (A)
– Statin therapy* (A)
• In patients with a prior MI
– Beta-blockers should be continued for at least 2 years after
the event (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S32.
Recommendations: Nephropathy
• To reduce risk or slow the progression of
nephropathy
–Optimize glucose control (A)
–Optimize blood pressure control (A)
Screening the other complications
+++and the other cardio vascular risks
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.
ADA Recommendations:
• Smoking : Advise all patients not to smoke (A)
• Include smoking cessation counseling and other
forms of treatment as a routine component of
diabetes care (B)
Physical Activity : Advise people with diabetes to
perform at least 150 min/week of moderate-intensity
aerobic physical activity (50-70% of maximum heart rate)
(A)
Diabetes Self-Management Education
Life style ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S32.
Clinical Case
• Mr M, 65 year- old -man
 Diabetes since 11 years : metformin : 2000 mg/day,
glibenclamide: 10 mg/day
 Hypertension since 4 years : nifedipine : 40 mg/day
 Smoking : 10 cigaretts / day
Chest pain  ICU
Diagnosis: acute MI : ST +
Glycemia: 13 mmol/l, Hb A1c: 9%, TRP positive, creatinin:
1OO µmol/l, LDLc: 1.4 g/l, Tg: 1.1 g/l, HDL c: 0.5 g/l
What do you recommend ?
Clinical Case
• Diabetes :
• metformin : 2000 mg/day,
• Stop glibenclamide: 10 mg/day and switch on
gliclazide, glimepiride or insulin
Hypertension: stop nifedipine : SRAA blocker and Betablockers
Antiplatelet Agents +++
Lipids : statins
 stop smoking
Education and screening of the other complications
and risks
• MI : ST + : cardilogist recommends?
Conclusion
• Diabetes Mellitus is associated with adverse
cardiovascular prognosis.
• DM have added risk of cardiovascular
mortality after ACS.
•PRIMARY
Common conditions
with type 2
ANDcoexisting
SECONDARY
diabetes (e.g., hypertension, dyslipidemia) are
PREVENTION
clear risk factors for CVD
• Perspectives: how to reduce the mortality of
patients with DM and ACS to a rate
comparable to patients without DM?
Téléchargement
Explore flashcards