Transcript Diapositiva 1 - Gastaldi Congressi

Thirteenth International Symposium
HEART FAILURE & Co.
Il Mio Dolce Cuore
My Sweet Heart
Napoli
12-13 aprile 2013
Stroke in Diabetics, the
Lesson from NOAs
E. Gronda, FESC, FANMCO
Divisione di Cardiologia
Dipartimento Cardiovascolare
IRCCS, MultiMedica - S.S. Giovanni
Ospedale Classificato S. Giuseppe - Milano
Gruppo MultiMedica
• 23% of Ischemic Strokes
are Cardiogenic, the more
severe
• DM commonly associated with AF on an epidemiological basis [1]
• A clustering of risk factors: insulin resistance, lipid abnormalities and hypertension
(the metabolic syndrome), links diabetes to other risk-factors,
•
endothelial dysfunction bears:
• proinflammatory states, haemostasis/fibrinolysis abnormalities,
angiogenesis, extracellular matrix turnover [2,3]
•
abnormal sympathetic tone links to
• left ventricular hypertrophy, cardiac dysfunction, and autonomic
neuropathy [4]
•
abnormalities in inflammatory and thrombotic states impair
the ability of myocardial and vascular tissue to remodel, to recover
and to sustain functionality [5].
1.
2.
3.
4.
5.
Kannel WB et al. N Engl J Med 1982;306(17):1018– 2.
Grundy SM et al. Circulation 2004 (Jan 27); 109(3):433–8.
Tayebjee MH et al. Diabetes Care 2004 (Aug);27(8):2049– 51.
Lim HS Arch Intern Med 2004 (Sep 13);164(16):1737– 48.
Lip GY et al. Eur Heart J 2000 (Oct);21(20):1653– 65.
•
VHAH study [1]:
AF occurrence in 14.9% of DM pts vs 10.3% in control group (p<0.0001)
On multi-variate analysis :
• DM independently associated with AF (OR of 2.13, 95% CI: 2.10–2.16; p <0.0001)
and Flutter (OR 2.20, CI: 2.15 – 2.26; p <0.0001).
• Independently associated with DM: . HF (OR 3.1), LVH (OR 1.85), CAD (OR 2.39.
• VALUE trial [2]:
DM linked to
•
•
•
significant increase of new-onset of AF (RR 1.49, P=0.0031)
higher chance of developing persistent AF (RR 1.87, P=0.0014).
diabetics presenting AF new-onset have much higher occurrence of HF (RR 3.56, P<0.0001)
• Large Nichols’ follow up study (7.2±2.8-year) [3],
•
Risk of AF occurrence increased by 26% in diabetic women
• Prevalence of abnormal glucose metabolism in AF (75 y.o. patients) [4]:
•
•
AF occurrence could be associated with long-term hyperglycemia
AF history >5 years, proactive DM pre-diabetes screening to be performed.
1.
2.
3.
4.
Movahed MR, et al. Int J Cardiol 2005;105:315– 8.
Aksnes TA et al,.Am J Cardiol 2008;101:634 – 638
Nichols CA et al. Diabetes care,vol.32,no.10,pp.1851-1856,2009.
Johansen OE et al. Cardiovascular diabetology ,vol 7, no.28, 2008.
Independent risk factors for AF
in patients with sinus rhythm
Framingham
Odds ratio*
Men (n = 2090)
Women (n = 2641)
Heart failure
4.5
Age (for every 10 years)
2.1
Valvular heart disease
1.8
Hypertension
1.5
Diabetes
1.4
Myocardial infarction
1.4
0
1
2
3
5.9
2.2
3.4
1.4
1.6
NS
4
5
6
7
0 1 2 3 4 5 6 7 8 9
*2-year pooled logistic regression
Benjamin EJ, et al. JAMA. 1994;271:840-844.
Impact of Glucose Intolerance and Insulin Resistance on
Atrium Size
Quartiles of Homa - IR
• Women (n=1170)
• Men (n=852)
Echo
LA,
cm
Q1
Q2
Q3
Q4
P - for
Trend
1
3,90
3,94
3,97
4,06
<0,001
2
3,98
3,98
3,96
3,95
3
3,98
3,97
3,97
3,95
HOMA-IR
range U
0.18–
0.940.
0.95–
1.57
1.58–
2.60
2.61–
12.09
Echo
LA,
cm
Q1
Q2
Q3
Q4
P - for
Trend
1
3,39
3,48
3,48
3,58
<0,001
0,42
2
3,47
3,50
3,48
3,48
0,42
0,56
3
3,47
3,50
3,47
3,48
0,56
HOMA-IR
range U
0.16–
0.700.
0,71–
1.231.
1,24–
1.971.
1,98–
14.38
Rutter MK et al. Circulation. 2003;107:448-454
Clinical Correlates in the Community Longitudinal
Tracking of Left Atrial Diameter Over the Adult Life Course
1.
Low risk group : BMI of 25 kg/m2 with normal BP (defined as having a median BP of
113/73)
2.
Intermediate risk group: BMI of 27.5 kg/m2 and pre-hypertension (defined as having
a median BP of 133/86) not receiving anti-hypertensive medications
3.
High risk group : BMI of 30 kg/m2 and hypertension (defined as having a median BP
of 146/91 ).
McManus DD et al. Circulation 2010;121;667-674
Gender ♀%
84
Age yrs
65 ±10
0.61
Creat.(mg/dl)
1,4±0,7
Diabetes M %
61
78
p Value
0.28
67 ± 10
1,0±0,3
35
Melenovsky V. et al. J Am Coll Cardiol 2007;49:198–207
<0,01
<0,01
(Toh, Hypertension 2010)
100
90
80
70
60
Percentage of Administration of ANTICOAGULATION THERAPY in
Patients with Atrial Fibrillation
(the Euro Heart Survey).
Stroke risk: is the Atrial Fibrillation pattern a rationale risk stratification criteria?
• Similar risk for thromboembolic events in paroxysmal versus sustained
AF in patients under treatment
• This risk can be significantly lowered with OAC
• Only intermittent monitoring used in this study
S. Hohnloser. J Am Coll Cardiol 2007; 50: 2156–61
From: Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry
of Atrial Fibrillation
JAMA. 2001;285(22):2864-2870. doi:10.1001/jama.285.22.2864
Figure Legend:
-
-
+
+
Copyright © 2012 American Medical
Association. All rights reserved.
The anticoagulation strategy mainly should depend of CHA2DS2-VASc score
instead of the type of AF (paroxysmal, persistent or permanent).
CHA2DS2VASc better identifies patients at
intermediate risk !
CHA2DS2VASc SCORE
Stroke Risk Factor
CHADS2 Score
Stroke Risk Factor
1.
2.
3.
4.
5.
Congestive heart failure
Hypertension
Age ≥75 years
Diabetes mellitus
Stroke, TIA, or
thromboembolism
1
1
1
1
1.
2.
3.
4.
5.
2
6.
7.
8.
Maximum score
6
Congestive heart failure/
LV dysfunction
Hypertension
Age ≥75 years
Diabetes mellitus
Stroke, TIA, or
thromboembolism
Vascular disease
(previous MI, PAD, or
aortic plaque)
Age 65–74 years
Gender category (female)
Maximum score
LV=left ventricular. MI=myocardial infarction. PAD= peripheral artery disease.
1
1
2
1
2
1
1
1
9
Score at baseline and stroke rate at 1 year according to CHADS2 and CHA2 DS2VASc scores
(after AMI #73 538)
CHADS2
CHA2DS2VASc
Proportion of patients
with score
Stroke rate at 1 year
(95% CI)
Proportion of patients
with score
Stroke rate at 1 year
(95% CI)
22%
1·7% (1·5–1·9)
8%
0·8% (0·6–1·0)
31%
4·7% (4·4–5·1)
12%
2·0% (1·7–2·4)
23%
7·3% (6·9–7·8)
18%
3 ·7% (3·3–4·1)
15%
15·5% (14·6–16·3)
23%
5·9% (5·5–6·3)
7%
21·5% (20·0–23·2)
19%
9·3% (8·7–9·9)
2%
19·7% (16·9–22·9)
12%
15·3% (14·3–16·2)
0·2%
22·4% (14·6–34·3)
6%
19·7% (18·2–21·4 )
2%
21·5% (18·7–24·6)
0·4%
22·4% (16·3–30·8)
0·1%
23·6% (10·6–52·6)
0
1
2
3
4
5
6
7
8
9
Mark J A, Lancet Neurol 2012; 11: 1066–81
Dabigatran treatment effects consistent in patients
at higher and lower risk of myocardial ischemic events.
Hohnloser SH et al. Circulation. 2012;125:669-676
Diabetes, a Stroke specific risk factor?
•
•
•
•
CHADS2VASC Risk factors
Diabetes links
•Diabetes (if present)
•Hypertension
1
1
•Age >75
•Age 65-74
2
1
♂ 17,9% - ♀ 20,6% diabetes [2]
♂ 15,3% - ♀ 12,4% diabetes
•Stroke
2
incidence per year in diabetics
♂ 13,7/1000
♀ 10,8/1000
when one or more CVD present [3]
•Vascular disease
hypertension,
1
In a cohort (aged >65 years) with
roughly half had PAD (ABI <1.0) [4]
Tarnw L et al. Diabetes Care 1994 Nov;17(11):1247-51
Giorda CB et al Stroke. 2007;38:1154-1160
http://www3.istat.it/dati/catalogo/20111216_00/
1Newman AB et al. Circulation. 1993;88:837-845.
40% in NIDDM
>80% in IDDM with macroalbuniria [1]
Comparison of Dabigatran versus Warfarin in Diabetic Patients with Atrial Fibrillation: Results from the RE-LY Trial
Darius AHA 2012, Abstract No. 15937
Diabetes
Annual rate
dabigatran
150 mg bid
Annual rate
dabigatran
110 mg bid
Annual rate
warfarin
DE 150 mg vs
warfarin HR (95% CI)
DE 110 mg vs
warfarin HR (95% CI)
No
1.01
1.47
1.52
0.66 (0.51, 0.86)
0.97 (0.76, 1.23)
Yes
1.46
1.76
2.35
0.62 (0.42, 0.91)
p-inter = 0.7555
0.74 (0.51, 1.08)
p-inter = 0.2349
Ischemic stroke
(incl. Uncertain)
No
Yes
0.82
1.28
1.25
1.62
1.08
1.65
0.76 (0.56, 1.02)
0.77 (0.49, 1.20)
p-inter = 0.9553
1.16 (0.89, 1.52)
0.98 (0.65, 1.47)
p-inter = 0.4839
Major bleeding
No
Yes
2.92
4.66
2.59
3.81
3.38
4.19
0.86 (0.73, 1.02)
1.12 (0.87, 1.44)
p-inter = 0.0917
0.76 (0.64, 0.90)
0.91 (0.70, 1.19)
p-inter = 0.2656
Intracranial bleeding
No
Yes
0.27
0.47
0.23
0.22
0.75
0.81
0.36 (0.23, 0.57)
0.58 (0.29, 1.16)
p-inter = 0.2446
0.31 (0.19, 0.50)
0.26 (0.11, 0.65)
p-inter = 0.2656
Vascular death
No
Yes
1.93
3.46
2.17
3.27
2.29
4.01
0.84 (0.69, 1.02)
0.86 (0.65, 1.13)
p-inter = 0.8788
0.95 (0.78, 1.15)
0.81 (0.62, 1.07)
p-inter = 0.3794
Death
No
Yes
3.20
5.15
3.45
4.74
3.71
5.51
0.86 (0.74, 1.00)
0.93 (0.74, 1.17)
0.93 (0.79, 1.08)
0.85 (0.68, 1.08)
Outcome
Stroke +
systemic embolism
17
CHA2DS2VASc Score vs HAS-BLED Score
a fair balance?
CHA2DS2VASc SCORE
Stroke Risk Factor
HAS-BLED Score
Bleeding Risk Factor
1.
1.
2.
2.
3.
4.
5.
6.
7.
8.
Congestive heart failure/
LV dysfunction
Hypertension
Age ≥75 years
Diabetes mellitus
Stroke, TIA, or
thromboembolism
Vascular disease
(previous MI, PAD, or
aortic plaque)
Age 65–74 years
Gender category (female)
Maximum score
1
1
2
1
2
3.
4.
5.
6.
7.
Hypertension
Abnormal renal /liver function
(1 pt. each)
Stroke
Bleeding
Labile INRs
Elderly (age > 65 years)
Drugs or alcohol (1pt. each)
1
1 or 2
1
1
1
1
1 or 2
1
1
1
9
Max Score
LV=left ventricular. MI=myocardial infarction. PAD=peripheral artery disease.
9
Net clinical benefit for warfarin, dabigatran, rivaroxaban and apixaban
by CHA2DS2-VASc
Banerjee A et al. Thromb Haemost 2012; 107: 584–589
Net clinical benefit for warfarin, dabigatran, rivaroxaban and apixaban
by CHA2DS2-VASc and HAS-BLED ≤2.
Banerjee A et al. Thromb Haemost 2012; 107: 584–589
Key Messages
• NOAs (dabigatran, rivaroxaban and apixaban) tested in large
randomized controlled multicenter international trials, although with
different study design, show favourable effects on both
ischaemic stroke/thromboembolism
and
bleeding risk.
Regardless of associated medical conditions, including
diabetes.
•
The net clinical benefit balancing ischaemic stroke against
intracranial haemorrhage is only negative with warfarin at a
CHA2DS2-VASc score=0, reflecting the ‘truly low risk’ status of
these patients
Key Messages
• Diabetes per se, runs increasing risk of atrial fibrillation & stroke by
clustering a number of cardiovascular risk factors in the same
patient.
• Multiple noxae hit cardiovascular apparatus and haemocoagulative system exposing diabetic patient to the opposite risk
of thrombus and of bleeding.
• The preventive NOAs administration in this high risk subpopulation
have shown, in the balance, a prominent net clinical benefit over
bleeding risk, as well as in the overall treated population.
Key Messages
What does Banerjee’s paper add?
● In patients with CHA2DS2-VASC =0 but at high bleeding risk, apixaban and
dabigatran 110 mg bid have a positive net clinical benefit.
● At CHA2DS2-VASc=1, apixaban and both doses of dabigatran (110 mg
and 150 mg bid) have a positive net clinical benefit.
● In patients with CHA2DS2-VASC score ≥1 or ≥2, the three new NOAs
(dabigatran, rivaroxaban and apixaban) appear superior to warfarin for net
clinical benefit, regardless of risk of bleeding.
● When risk of bleeding and stroke are both high, all three new drugs
appear to have a greater net clinical benefit than warfarin.