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Cerebrovascular prevention in cardiac failure George Ntaios University of Thessaly, Larissa, Greece Lausanne 6/09/2012.

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Presentation on theme: "Cerebrovascular prevention in cardiac failure George Ntaios University of Thessaly, Larissa, Greece Lausanne 6/09/2012."— Presentation transcript:

1 Cerebrovascular prevention in cardiac failure George Ntaios University of Thessaly, Larissa, Greece Lausanne 6/09/2012

2 J Card Fail 2006; 12:39-46 StudyNYHA class (median) EFStroke rate (per year) AF SAVE1.7271.3%0% SOLVD1311.5%10% Katz et al.2.5271.7%13% V-HEFT II2 or 3291.9%13% Cioffi et al.2.7232.0%16% V-HEFT I2 or 3302.0%16% Stroke risk in cardiac failure

3 N Engl J Med 1997; 336:251-7 Stroke risk increases with ↓ejection fraction [ SAVE trial ]

4 J Thromb Haemost 2007; 5: 224–31 J 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 A 2, etc. Pathophysiology of thrombus

5 Atrial fibrillation Sinus rhythm

6 CHADS 2 C ongestive heart failure1 H ypertension1 A ge ≥ 75 years1 D iabetes Mellitus1 S troke/TIA/VTE2 CHADS 2 = 0 No treatment CHADS 2 = 1 OAC or Aspirin CHADS 2 ≥ 2 OAC CHA 2 DS 2 - VASc C ongestive heart failure1 H ypertension1 A ge ≥ 75 years2 D iabetes Mellitus1 S troke/TIA/VTE2 V ascular disease1 A ge 65 - 74 years1 S ex (female)1 CHA 2 DS 2 – VASc = 0 No treatment CHA 2 DS 2 – VASc = 1 OAC > Aspirin CHA 2 DS 2 – VASc ≥ 2 OAC Stroke prevention in patients with cardiac failure & atrial fibrillation

7 Sinus rhythm

8 Am Heart J 2004; 148:157–64 The Warfarin/Aspirin Study in Heart Failure (WASH)

9 Am Heart J 2004; 148:157–64 The Warfarin/Aspirin Study in Heart Failure (WASH)

10 Am Heart J 2004; 148:157–64 Composite event: - Death - Non-fatal stroke - Non-fatal MI The Warfarin/Aspirin Study in Heart Failure (WASH)

11 Eur J Heart Failure 2006; 8:428–32 The Heart failure Long-term Antithrombotic Study (HELAS)

12 Eur J Heart Failure 2006; 8:428–32 The Heart failure Long-term Antithrombotic Study (HELAS)

13 Cochrane Database of Systematic Reviews 2012; 6: CD003336 Warfarin vs. placebo: All-cause deaths

14 Cochrane Database of Systematic Reviews 2012; 6: CD003336 Warfarin vs. placebo: Cardiovascular events

15 Cochrane Database of Systematic Reviews 2012; 6: CD003336 Warfarin vs. placebo: Major hemorrhages

16 Circulation. 2009; 119:1616-24 Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)

17 Circulation. 2009; 119:1616-24 Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)

18 Circulation. 2009; 119:1616-24 Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH) Composite event: - Death - Non-fatal stroke - Non-fatal MI

19 Circulation. 2009; 119:1616-24 Mortality Warfarin & Antiplatelet Therapy in Chronic Heart Failure (WATCH)

20 N Engl J Med. 2012; 366(20):1859-69 Warfarin & Aspirin with Heart Failure & Sinus Rhythm (WARCEF)

21 N Engl J Med. 2012; 366(20):1859-69

22 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

23 Warfarin & Aspirin with Heart Failure & Sinus Rhythm (WARCEF) OutcomeWarfarin N=1142 Aspirin N=1163 HR 95%CI P-value Primary outcome 302 (26.4%)320 (27.5%)0.93 (0.79-1.10) 0.40 Death268 (23.5%)263 (22.6%)1.01 (0.85-1.20) 0.91 Ischemic stroke29 (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

24 WASHWarfarinAspirinPlaceboNS HELASWarfarinAspirinPlaceboNS WATCHWarfarinAspirinClopidogrelNS WARCEFWarfarinAspirinNS 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

25 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


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