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Cerebrovascular prevention in cardiac failure. George Ntaios University of Thessaly, Larissa, Greece. Lausanne 6/09/2012. Stroke risk in cardiac failure. J Card Fail 2006; 12:39-46. Stroke risk increases with ↓ejection fraction [ SAVE trial ]. N Engl J Med 1997; 336:251-7. - PowerPoint PPT Presentation
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Cerebrovascular preventi on in cardiac failure
G e o r g e N ta i o s
U n i v e r s i t y o f T h e s s a l y, L a r i s s a , G r e e c e
L a u s a n n e6 / 0 9 / 2 0 1 2
J Card Fail 2006; 12:39-46
Study NYHA class (median)
EF Stroke rate (per year)
AF
SAVE 1.7 27 1.3% 0%SOLVD 1 31 1.5% 10%Katz et al. 2.5 27 1.7% 13%V-HEFT II 2 or 3 29 1.9% 13%Cioffi et al. 2.7 23 2.0% 16%V-HEFT I 2 or 3 30 2.0% 16%
Stroke risk in cardiac failure
N Engl J Med 1997; 336:251-7
Stroke risk increases with ↓ejection fraction [ SAVE trial ]
J Thromb Haemost 2007; 5: 224–31J Am Coll Cardiol 1999; 33;1424-26
Abnormalities of Blood Flow Abnormalities of Blood Constituents
- Virchow’s triad
Abnormalities of Vessel Wall
- Atrial fibrillation- Low cardiac output- Poor contractility- Aberrant flow in dilated chambers
Fibrinogen, vWf, thrombin, fibrin, d-dimers, platelet volume,
β-thromboglobulin, p-selectin, etc.
Nitric oxide, prostacyclin, endothelin, vWf levels, thromboxane A2, etc.
Pathophysiology of thrombus
A t r i a l fi b r i l l a ti o n S i n u s r h y t h m
CHADS2
C ongestive heart failure 1
H ypertension 1
A ge ≥ 75 years 1
D iabetes Mellitus 1
S troke/TIA/VTE 2
CHADS2 = 0 No treatment
CHADS2 = 1 OAC or Aspirin
CHADS2 ≥ 2 OAC
CHA2DS2 - VASc
C ongestive heart failure 1
H ypertension 1
A ge ≥ 75 years 2
D iabetes Mellitus 1
S troke/TIA/VTE 2
V ascular disease 1
A ge 65 - 74 years 1
S ex (female) 1
CHA2DS2 – VASc = 0 No treatment
CHA2DS2 – VASc = 1 OAC > Aspirin
CHA2DS2 – VASc ≥ 2 OAC
Stroke prevention in patients with cardiac failure & atrial fibrillation
Sinus rhythm
Am Heart J 2004; 148:157–64
The Warfarin/Aspirin Study in Heart Failure (WASH)
Am Heart J 2004; 148:157–64
The Warfarin/Aspirin Study in Heart Failure (WASH)
Am Heart J 2004; 148:157–64
Composite event:- Death- Non-fatal stroke- Non-fatal MI
The Warfarin/Aspirin Study in Heart Failure (WASH)
Eur J Heart Failure 2006; 8:428–32
The Heart failure Long-term Antithrombotic Study (HELAS)
Eur J Heart Failure 2006; 8:428–32
The Heart failure Long-term Antithrombotic Study (HELAS)
Cochrane Database of Systematic Reviews 2012; 6: CD003336
Warfarin vs. placebo: All-cause deaths
Cochrane Database of Systematic Reviews 2012; 6: CD003336
Warfarin vs. placebo: Cardiovascular events
Cochrane Database of Systematic Reviews 2012; 6: CD003336
Warfarin vs. placebo: Major hemorrhages
Circulation. 2009; 119:1616-24
Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)
Circulation. 2009; 119:1616-24
Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)
Circulation. 2009; 119:1616-24
Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)
Composite event:- Death- Non-fatal stroke- Non-fatal MI
Circulation. 2009; 119:1616-24
Mortality
Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)
N Engl J Med. 2012; 366(20):1859-69
Warfarin & Aspirin with Heart Failure & Sinus Rhythm (WARCEF)
Warfarin & Aspirin with Heart Failure & Sinus Rhythm (WARCEF)
N Engl J Med. 2012; 366(20):1859-69
Warfarin & Aspirin with Heart Failure & Sinus Rhythm (WARCEF)
N Engl J Med. 2012; 366(20):1859-69
Composite end-point-Ischemic stroke-Intracerebral hemorrhage-Death
Warfarin & Aspirin with Heart Failure & Sinus Rhythm (WARCEF)
Outcome WarfarinN=1142
AspirinN=1163
HR95%CI
P-value
Primary outcome
302 (26.4%) 320 (27.5%) 0.93 (0.79-1.10)
0.40
Death 268 (23.5%) 263 (22.6%) 1.01 (0.85-1.20)
0.91
Ischemic stroke 29 (2.5%) 55 (4.7%) 0.52 (0.33-0.82)
0.005
Intracerebral hemorrhage
5 (0.4%) 2 (0.2%) 2.22 (0.43-11.66)
0.35
Major hemorrhage
66 (5.8%) 31 (2.7%) 2.21 (1.42-3.47)
<0.001
N Engl J Med. 2012; 366(20):1859-69
WASH Warfarin Aspirin Placebo NS
HELAS Warfarin Aspirin Placebo NS
WATCH Warfarin Aspirin Clopidogrel NS
WARCEF Warfarin Aspirin NS
Stroke prevention in patients with cardiac failure & sinus rhythm
- Warfarin is not better than aspirin or clopidogrel
- Warfarin or aspirin are not better than placebo
Clinical practice
In patients with HF and AF:- Oral anticoagulation is recommended.
In patients with HF and sinus rhythm:- There is no reason to use warfarin routinely. - Aspirin should not be given (unless there is a specific indication, such as documented coronary artery disease or previous stroke).
Eur J Heart Fail. 2012;14(7):681-95