Dipyridamole Plus Aspirin in Cerebrovascular Disease

Stroke is the leading cause of adult disability and dependency in western society. Following stroke, the risk of myocardial infarction (MI) is increased by a factor of around 2–3 compared with baseline. Indeed, after the first 30 days, stroke survivors are more likely to die from a cardiac event than from a cerebrovascular event. In patients with atherothrombotic stroke, preventing subsequent manifestations of the underlying disease is therefore an important therapeutic goal. A number of options have been shown to reduce the risk of stroke. Aggressively controlling stroke risk factors, such as hypertension, diabetes and smoking, should provide significant benefit in reducing stroke risk; however, it is difficult to realize the full potential of these approaches in routine clinical practice. A number of classes of medication can reduce the risk of stroke and other vascular events, including antiplatelet agents, anticoagulants, angiotensin-converting enzyme inhibitors and statins. Several antiplatelet agents are approved to reduce the risk of recurrent stroke, although only clopidogrel and acetylsalicylic acid (ASA) are approved for the reduction of both stroke and MI in such patients. In the CAPRIE study, clopidogrel showed a statistically significant relative risk reduction of 8.7% (p = 0.043) compared with ASA for the composite endpoint of ischaemic stroke, MI or vascular death. Evidence from animal studies, ex vivo models in humans, and patients undergoing coronary stent insertion or patients with unstable angina/non-Q-wave MI clearly demonstrates the synergistic antiplatelet effect of using clopidogrel with ASA. In summary, most patients with an ischaemic stroke should be treated with an antiplatelet agent to reduce their risk of recurrent stroke, MI, or vascular death. The use of aggressive antiplatelet therapy has the potential to become a new paradigm for managing patients with vascular disease due to atherothrombosis.

Section: Antiplatelet Therapy For Secondary Prevention In Stroke Patimentioning

confidence: 99%

Secondary Prevention of Stroke and the Expanding Role of the Neurologist

Alberts¹

2002

“…In the Antiplatelet Trialists’ overview, the addition of dipyridamole to aspirin among around 5,000 high-risk patients did not seem to produce any reduction in vascular events, but the possibility of a small additional benefit was not excluded [6]. When data from a further 3,000 patients in the ESPS2 study [16]are added, the combination of dipyridamole and aspirin is associated with a non-significant reduction of 10% (95% CI: 0–20%) in the odds of a vascular event [36]. Most of this reduction appears to be attributable to a 23% reduction in non-fatal strokes, suggesting that the addition of dipyridamole to aspirin may be appropriate for patients at particularly high risk of stroke [36].…”

Section: Current Evidence For Oral Antiplatelet Agentsmentioning

confidence: 99%

“…When data from a further 3,000 patients in the ESPS2 study [16]are added, the combination of dipyridamole and aspirin is associated with a non-significant reduction of 10% (95% CI: 0–20%) in the odds of a vascular event [36]. Most of this reduction appears to be attributable to a 23% reduction in non-fatal strokes, suggesting that the addition of dipyridamole to aspirin may be appropriate for patients at particularly high risk of stroke [36]. A detailed overview of all trials that have assessed the addition of dipyridamole to aspirin is currently being prepared by the Antithrombotic Trialists’ Collaboration [37], and further large randomized trials are currently in progress to determine more reliably the possible benefits of adding dipyridamole to aspirin [38].…”

Section: Current Evidence For Oral Antiplatelet Agentsmentioning

confidence: 99%

Current Oral Antiplatelet Agents to Prevent Atherothrombosis

Hankey¹

2001

Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2–19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59–0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0–20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.

“…However, more clinical data may be needed before there is widespread acceptance of the efficacy of the combination of dipyridamole and aspirin, especially in the light of numerous previous reports that showed only a weak effect of dipyridamole [28]. The European and Australian Stroke Prevention in Reversible Ischemia Trial is randomizing patients with a TIA or nondisabling stroke to daily doses of aspirin (30–325 mg) versus warfarin (INR 2–3) versus aspirin (30–325 mg) plus dipyridamole (400 mg).…”

Section: Dipyridamolementioning

confidence: 99%

Update on Clinical Trials of Antiplatelet Therapy for Cerebrovascular Diseases

Bhatt

Kapadia²,

Yadav³

et al. 2000

Antiplatelet medications are an important part of the therapy of cerebrovascular diseases. Oral agents such as aspirin have an established role in the secondary prevention of stroke. An aspirin and dipyridamole combination has recently been approved. Ticlopidine has been proven to be more effective than aspirin, but its potentially serious side effect profile makes long-term use hazardous. Clopidogrel has been demonstrated to be both more effective than and at least as safe as aspirin. The combination of clopidogrel plus aspirin represents the likely future therapy for high-risk patients. The role of oral antiplatelet therapy in the acute treatment of stroke is beginning to be clarified. Aspirin treatment appears to be strongly indicated. Intravenous antiplatelet therapy with glycoprotein IIb/IIIa inhibitors for acute stroke and as an adjunct to carotid artery stenting appears promising.