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