Aspirin stroke prevention

Dipyridamole is a PDE5/PDE6 selective inhibitor that is used widely in conjunction with aspirin to reduce clotting and prevent stroke. More recent studies with a fixed combination of these two drugs (Aggrenox) has been shown in the recent European Stroke Prevention Study 2 to be of greatly added benefit over aspirin alone for prevention of recurrent stroke. 

The European Stroke Prevention Study 2 (ESPS-2) trial examined four treatment arms—extended-release dipyridamole (ER-DP) 200 mg twice daily alone, aspirin 25 mg twice daily alone, ER-DP 200 mg twice daily + aspirin 25 mg twice daily, or placebo. In comparison with placebo the overall reduction in stroke risk was 16% with ER-DP alone and 18% with aspirin alone. The combination of ER-DP and aspirin led to a 37% reduction in stroke risk compared to placebo. Compared with aspirin alone, the combination of ER-DP with aspirin reduced the risk of stroke by 23%. 

The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) confirmed the finding of ESPS 2, showing that the combination of aspirin and dipyridamole is more effective than aspirin alone in the prevention of new vascular events in patients with nondisabling cerebral ischaemia of presumed arterial origin. Adding the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or MI of 0.82 (95% Cl 0.74-0.91). 

Stroke Prevention All patients with paroxysmal, persistent, or permanent AF should receive therapy for stroke prevention, unless compelling contraindications exist. A decision strategy for stroke prevention in AF is presented in Fig. 6-9.27 In general, most patients require therapy with warfarin in some patients with no additional risk factors for stroke, aspirin may be acceptable. For some patients, serious consideration of the benefits of warfarin versus the risks of bleeding associated with warfarin therapy is warranted. The potential bleeding risks associated with warfarin may outweigh the benefits in... 

Randomized trials have been completed assessing the role of antiplatelet therapy with aspirin for primary stroke prevention. The use of aspirin in patients with no history of stroke or ischemic heart disease reduced the incidence of non-fatal myocardial infarction (MI) but not of stroke. A meta-analysis of eight trials found that the risk of stroke was slightly increased with aspirin use, especially hemorrhagic stroke. Major bleeding risk was also increased with aspirin use.4 Aspirin is beneficial in the primary prevention of MI, but not for primary stroke prevention. 

Ticlopidine is slightly more beneficial in stroke prevention than aspirin in both men and women.31,32 The usual recommended dosage is 250 mg orally twice daily. Ticlopidine is costly, and side effects include bone marrow suppression, rash, diarrhea, and an increased cholesterol level. Neutropenia is seen in approximately 2% of patients. Thrombotic thrombocytopenic... 

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 ... 

Q10 If a patient is thought to be at risk of a stroke, would an antiplatelet agent, such as aspirin, be suitable for stroke prevention ... 

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).

Few trials of antiplatelet agents have distinguished between different vascular territories or mechanisms of stroke, but there are some data on antiplatelet agents in posterior circulation disease. The Canadian Cooperative Study Group (1978) showed that aspirin reduced recurrent episodes of cerebral ischemia and death in patients with vertebrobasilar events. The European Stroke Prevention Study (ESPS Sivenius et al. 1991) of aspirin and immediate-release dipyridamole versus placebo appeared to show that patients with posterior circulation TIA benefited more than those with carotid disease, but the numbers of events were too small to be certain. 

Diener HC, Cunha L, Forbes C et al. (1996). European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. Journal of the Neurological Sciences 143 1-13 Diener HC, Bogousslavsky J, Brass LM et al. (2004). Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH) randomised double-blind placebo-controlled trial. 

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... 

Aspirin, one of the oldest pharmceutical products, has been produced for over a hundred of years [4]. A chemist, Felix Hoffmann, who worked for the Bayer Co. in Elberfeld, Germany, discovered aspirin. He was searching for a medication for pain relief for his father who suffered from the pain of rheumatism. Besides pain relief, physicians have recently found that aspirin helps prevent heart attacks and strokes. 

In 1960, researchers found that aspirin has an antiplatelet activity it keeps blood cells called platelets from forming clots. Today the U.S. Food and Drug Administration and other regulatory agencies throughout the world approve aspirin to reduce the risk of having a stroke, for immediate treatment of a possible heart attack, and to prevent second heart attacks. A study of fifty-five thousand patients showed that daily aspirin can prevent a first heart attack in apparently healthy individuals, reducing their risk by 32 percent. 

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. 

Barnett HJM, Kaste M, Mdckum H, Eliasziw M. Aspirin dose in stroke prevention. Beautiftil hypotheses... 

Assessing the benefit-to-harm balance of low-dose aspirin in preventing strokes and heart attacks... 

Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O Fallon WM, Wiebers DO. Freqnency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention. A population-based study. Ann Intern Med 1999 130(l) 14-22. 

Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, Kamm B. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989 321(8) 501-7. 

In the Second European Stroke Prevention Study, headaches associated with dipyridamole (in 8% of patients taking dipyridamole or dipyridamole + aspirin... 

The predictive factors for headaches were explored in a study of the bioequivalence of two formulations of dipyridamole 200 mg in a modified-release combination with aspirin 25 mg (17). The conclusion was that the rapid fall in the incidence of headaches over time implied that most patients quickly develop tolerance to dipjridamole-associated headaches. However, in the European Stroke Prevention Study 2, headache was the most common adverse event, and it occurred more often in dipyridamole-treated patients (18). 

All patients who have had an acute ischemic stroke or TEA should receive long-term antithrombotic therapy for secondary prevention. In patients with noncardioembolic stroke, this will be some form of antiplatelet therapy. In a recent meta-analysis, the overall benefit of antiplatelet therapy in patients with atherothrombotic disorders was estimated to be 22%. Aspirin is the best-studied of the available agents and, until recently, was considered the sole first-line agent. However, published literature has supported the use of clopidogrel and the aspirin plus extended-release dipyridamole combination product (ERDP + ASA) as additional first-line agents in secondary stroke prevention. 

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