Aspirin atrial fibrillation

The Heparin in Acute Embolic Stroke Trial (HAEST) was a multicenter, randomized trial of the effect of LMWH (dalteparin 100 lU/kg sc twice daily) or aspirin (160 mg once daily) for the acute treatment of 449 patients with ischemic stroke and atrial fibrillation (AF). The primary outcome was the rate of recurrent stroke within 14 days. No difference in rates of early recurrence (8.5% dalteparin treated vs. 7.5% aspirin treated) or good 3-month functional outcome was found. The frequency of early slCH was 2.7% on dalteparin versus 1.8% on aspirin. 

Berge E, Abdelnoor M, Nakstad PH, Sandset PM, on behalf of the Haest Study Group. Low molecular-weight heparin versus aspirin in patients with acute ischemic stroke and atrial fibrillation a double blind randomised study. Lancet 2000 335 1205-1210. 

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

The risk of embolism associated with mechanical heart valves is 2 to 6% per patient per year despite anticoagulation and is highest with valves in the mitral position. Warfarin therapy (INR 2.5 to 3.5) is recommended in these patients. The addition of enteric-coated aspirin (100 mg/d) to warfarin (INR 3.0 to 4.5) in high-risk patients (preoperative atrial fibrillation, coronary artery disease, history of thromboembolism) with mechanical valves decreases the incidence of systemic embolism and death from vascular causes (1.9 vs. 8.5% per year), but increases the risk of bleeding. 

Rheumatic mitral valve disease is associated with thromboembolic complications at reported rates of 1.5 to 4.7% per year the incidence in patients with mitral stenosis is approximately 1.5 to 2 times that in patients with mitral regurgitation. The presence of atrial fibrillation is the single most important risk factor for thromboembolism in valvular disease, increasing the incidence of thromboembolism in both mitral stenosis and regurgitation four- to sevenfold. In current practice, patients with nonrheumatic atrial fibrillation at low risk for thromboembolism based on clinical characteristics frequently are treated with aspirin. Warfarin therapy is considered in higher-risk patients, especially those with previous thromboembolism and in whom anticoagulation is not contraindicated due to preexisting conditions. 

Recent evidence indicates that many patients with atrial fibrillation—a very common arrhythmia in the elderly—do as well with simple control of ventricular rate as with conversion to normal sinus rhythm. Of course, measures should be taken to reduce the risk of thromboembolism in chronic atrial fibrillation (aspirin or anticoagulant drugs). 

Lip GY Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation A systematic review and meta-analysis. Thromb Res 2006 ... 

Some of the association between atrial fibrillation and stroke must be coincidental because atrial fibrillation can be caused by coronary and hypertensive heart disease, both of which may be associated with atheromatous disease or primary intracerebral hemorrhage. Although anticoagulation markedly reduces the risk of first or recurrent stroke, this is not necessarily evidence for causality because this treatment may be working in other ways, such as by inhibiting artery-to-artery embolism, although trials of warfarin in secondary prevention of stroke in sinus rhythm have shown no benefit over aspirin (Ch. 24). 

Strachan DP, Carrington D, Mendall MA et al. (1999). Relation of Chlamydia pneumoniae serology to mortality and incidence of ischemic heart disease over 13 years in the Caerphilly Prospective Heart Disease Study. British Medical Journal 318 1035-1039 Stroke Prevention in Atrial Fibrillation Investigators (1992). Predictors of thromboembolism in atrial fibrillation II Echocardiographic features of patients at risk. Annals of Internal Medicine 116 6-12 Stroke Prevention in Atrial Fibrillation Investigators (1995). Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation the Stroke Prevention in Atrial Fibrillation Study. Journal of Stroke and Cerebrovascular Disease 5 147-157... 

Fig. 7.2. A patient presenting with atrial fibrillation and a transient ischemic attack was found to have a cerebellar microbleed on gradient echo MRI (a) and was started on stroke prevention with aspirin rather than warfarin. Six months later, this patient had a symptomatic hemorrhage at the same site (b).

Gage BF, van Walraven C, Pearce LA et al. (2004). Selecting patients with atrial fibrillation for anticoagulation. Stroke risk stratification in patients taking aspirin. Circulation 110 2287-2292 Giles MF, Rothwell PM (2007). Risk of stroke early after transient ischaemic attack a systematic review and meta-analysis. Lancet Neurology 6 1063-1072... 

Patients in atrial fibrillation who have a TIA or stroke without other clear etiology should be given anticoagulation therapy if there are no contraindications (European Atrial Fibrillation Trial Study Group 1993, 1995). Recent studies have shown that warfarin is as safe as aspirin in elderly patients with atrial fibrillation (Rash et al. 2007 Mant et al. 2007). Patients with presumed cardioembolic TIA or stroke secondary to other causes should certainly receive antithrombotic therapy. Also they may benefit from anticoagulation in certain circumstances, such as intracardiac mural thrombosis after myocardial infarction, although there have been no randomized trials in situations other than non-valvular atrial fibrillation. 

European Atrial Fibrillation Trial Study Group (1995). Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. New England Journal of Medicine 333 5-10 Halkes PH, van Gijn J For the ESPRIT Study Group (2006). Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT) randomised controlled trial. Lancet 367 1665-73 [Erratum in Lancet (2007) 369 274]... 

Mant J, Hobbs FD, Fletcher K et al. (2007) Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment... 

A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 36 151-156 Redman AR, Allen LC (2002). Warfarin versus aspirin in the secondary prevention of stroke the WARSS study. Current Atherosclerosis Reports 4 319-325... 

Apart from surgical and interventional therapy of occlusive carotid artery disease, the major approach to preventing vascular disease and subsequent stroke is to pay close attention to the control of modifiable risk factors such as hypertension, smoking, diabetes, and hypercholesterolemia. Coumadin, an anticoagulant, is effective for the primary and secondary prevention of stroke in patients with atrial fibrillation. Aspirin, clopidogrel, and the combination of aspirin and cUpyridamole have been proven to be effective for secondary stroke prevention along with the antihypertensive combination of indap-amide and perindopril. 

FIGURE 17-6. Algorithm for the treatment of atrial fibrillation and atrial flutter. Sx = symptoms AVN = AV node DCC = direct-current cardioversion CCB = calcium channel antagonist (verapamil or diltiazem) BB = jS-blocker ASA = aspirin OHD = organic heart disease AADs = antiarrhythmic drugs INR = international normalized ratio MVD = mitral valve disease CHF = congestive heart failure HTN = hypertension DM = diabetes mellitus. 

Gage BF, Cardinally AB, Abers GW, Owens DR. Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with non-valvular atrial fibrillation. JAMA 1995 274 1839-1845. 

In contrast, indobufen (Fig. 31.15), a reversible but very potent inhibitor of platelet COX-1 activity, was shown to have comparable clinical efficacy to that of aspirin in prevention of DVT after myocardial infarction and in blocking exercise-induced increase in platelet aggregation (99). In the secondary prevention of thromboembolic events, 100 or 200 mg of indobufen twice daily is as effective as warfarin or aspirin in patients with or without atrial fibrillation (100). Currently, indobufen is only available for routine clinical use in Europe. 

Stroke Prevention in Atrial Fibrillation Investigators. Adjusted-dose warfarin versus low-in-tensity, fixed dose warfarin plus aspirin for high-risk patients with atrial fibrillation Stroke Prevention in Atrial Fibrillation III randomised clinical ttial. Lancet (1996) 348, 633-8,... 

In a large study in patients with atrial fibrillation, the eumulative ineidence of bleeding events after 3 years was no different in those teeeiving fixed low-dose warfarin 1.25 mg daily plus aspirin 300 mg daily (24.4%) than with fixed low-dose warfarin alone (24.7%) or aspirin 300 mg daily alone (30%). This sfudy also confained an adjusted-dose warfarin-only group, which proved more effective than the other group, so the study was terminated early. Other studies have found similar results. ... 

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