Antiplatelet drugs for prevention of cerebral ischemic accidents]

Antiplatelet (AP) drugs play a major role in stroke prevention. Aspirin (50-1300 mg), ticlopidine (500 mg), clopidogrel (75 mg) and dipyridamole (400 mg) are effective in secondary prevention of atherothrombotic brain infarcts. Aspirin has been the most extensively studied drug and remains the most cost-effective one. The optimal dose is still debated; doses between 100 and 300 mg are the most widely used. The preventive efficacy of aspirin is already present at the acute phase of cerebral infarct. In primary prevention, aspirin nearly halves the risk of myocardial infarction but does not reduce that of stroke. Cardiac diseases with a high embolic risk require the use of oral anticoagulation. In non valvular atrial fibrillation, the choice of antithrombotic drugs depends on risk stratification: oral anticoagulants are indicated in high risk subjects whereas aspirin is recommended in low risk subjects and when oral anticoagulants are contraindicated. Studies with new associations of AP and with new drugs are required to increase the yield of the antiplatelet approach in high risk subjects; this should be done in parallel with efforts to detect and to treat the vascular risk factors associated with the development of a mass approach for stroke primary prevention.     

Secondary prevention of stroke

Stroke is a common disorder and a leading cause of disability and death. Ischaemia is a more common cause than haemorrhage and radiological imaging is required to accurately differentiate these. Some specific risk factors for stroke are non-modifiable--these include age, gender, racial and hereditary factors. Certain risk factors for ischaemic stroke can be identified and modification of these can be used for secondary prevention--examples include hypertension, heart diseases, atrial fibrillation, diabetes mellitus, dyslipidaemia, smoking, excessive alcohol consumption and carotid stenosis. Carotid endarterectomy is valuable in selected patients. In ischaemic stroke and transient ischaemic attack antithrombotic therapy is an option used in secondary prevention. In atrial fibrillation, warfarin should be used where possible in secondary prevention. When warfarin is contraindicated aspirin should be used. In other patients, an antiplatelet regime is appropriate--aspirin is commonly used and is the least expensive regime. Other antiplatelet agents such as dipyridamole, ticlopidine and clopidogrel may have a place. Younger patients with ischaemic stroke may have a thrombophilia state and should be appropriately investigated.     

Adding aspirin to clopidogrel after TIA and ischemic stroke: benefits do not match risks

Antiplatelet therapy is effective for reducing the risk of recurrent stroke and other serious vascular events in patients with recent TIA and ischemic stroke. Effective antiplatelet agents include aspirin, ticlopidine, clopidogrel, dipyridamole, and the combination of aspirin and dipyridamole. The combination of aspirin and clopidogrel is more effective than aspirin in patients with acute coronary syndrome but is more hazardous than clopidogrel alone in patients with recent TIA and ischemic stroke. Further trials are needed to determine whether the combination of aspirin and clopidogrel may have a role immediately after TIA and ischemic stroke in patients with symptomatic large artery atherothromboembolism and continued for approximately 3 months before switching to less hazardous antiplatelet regimens.     

Prevention of stroke recurrence

Stroke recurrence can be reduced substantially by intervention with the appropriate stroke preventive(s). Control of blood pressure, use of one of the antiplatelet agents aspirin, aspirin plus extended (modified)-release dipyridamole, or clopidogrel, administration of warfarin for patients with atrial fibrillation and high-risk profiles for stroke, and use of carotid endarterectomy in patients with high grades of symptomatic carotid artery stenosis are all proven therapies for prevention of stroke recurrence. Newer therapies to reduce the risk of infection and inflammation promise to further reduce the risk of first and recurrent stroke and are undergoing testing. In this article we review standard and more novel means to prevent stroke recurrence.     

Role of antiplatelet drugs in the prevention of cardiovascular events

Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A₂ (TXA₂)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with atherosclerotic vascular disease was more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction or vascular death. In the setting of coronary stenting, a double regimen including aspirin and ticlopidine or clopidogrel has proved more effective in the prevention of in-stent thrombosis than aspirin alone. Chronic oral administration of the inhibitors of platelet membrane receptor GP IIb/IIIa has been largely disappointing.     

EBM of cerebral infarction: message from mega-studies]

A meta-analysis by the Antithrombotic Trialists' Collaboration showed significant reduction of vascular events including stroke. MI, and vascular death by antiplatelet therapy in high risk patients with obstructive vascular disease. Low dose aspirin of 75 to 150 mg was most effective and its very low dose below 75 mg was not proven effective. Cilostazol significantly reduced the risk of recurrence in Japanese patients with ischemic stroke, mostly lacunar stroke. Large randomized controlled trials (RCTs) such as MATCH, ACTIVE, and CHARISMA are ongoing to see an effect of aspirin plus clopidogrel. Among patients with non-valvular atrial fibrillation (NVAF), warfarin is recommended in patients at age over 75 years, and those with history of stroke or TIA, hypertension, congestive heart failure, diabetes or coronary heart disease, while aspirin can be alternative in patients without any of these risk factors of stroke. Target INR of 2.0 to 3.0 is recommended in these NVAF patients, although lower INR of 1.6 to 2.5 is recommended to avoid hemorrhagic stroke in elderly patients with NVAF. SPORTIF was conducted to compare ximelagatran, an oral thrombin inhibitor, with warfarin in NVAF patients with risk factors, and the result showed a comparable efficacy and safety of ximelagatran. WARSS did not show any efficacy of warfarin over aspirin in any subtypes of ischemic stroke patients without NVAF, acute MI, left ventricular thrombi, or prosthetic heart valve. PICSS, a substudy of WARSS, also did not show any efficacy of warfarin over aspirin in stroke patients with patent foramen ovale (PFO), although warfarin might be recommended in PFO patients with deep vein thrombosis.     

An assessment of guidelines for prevention of ischemic stroke

OBJECTIVE: To compare methods and key management recommendations from recent stroke prevention guidelines. METHODS: Systematic review of guidelines for prevention of ischemic stroke published in English between 1996 and 2001 was conducted, and recommendations were independently abstracted and compared. RESULTS: Among 22 stroke prevention guidelines, information was provided about panel selection in 24%, funding source in 36%, consensus methods in 33%, and quantitative risk/benefit estimates in 38%. Eleven recommended anticoagulation for patients with atrial fibrillation at high risk for stroke, but eight different sets of criteria to identify high-risk patients were proposed. Recommendations regarding carotid endarterectomy for asymptomatic stenosis varied from general endorsement in a setting of low perioperative risk to routinely withholding surgery. All nine relevant guidelines endorsed aspirin in dosages between 50 and 325 mg/day for initial antiplatelet therapy following cerebral ischemia; six also suggested other antiplatelet agents as options for initial therapy. CONCLUSIONS: Current stroke prevention guidelines do not provide adequate methodologic information to permit assessment of their quality, potential bias, and clinical applicability. Management recommendations are relatively consistent but differ in several important areas.     

Antiplatelet Agents for Stroke Prevention

Stroke is one of the leading causes of disability and death. Ischemic stroke is a syndrome with heterogeneous mechanisms and multiple etiologies, rather than a singularly defined disease. Approximately one third of ischemic strokes are preceded by another cerebrovascular ischemic event. Stroke survivors are at high risk of vascular events (i.e., cerebrovascular and cardiovascular events), particularly during the first several months after the ischemic event. The use of antiplatelet agents remains the fundamental component of secondary stroke prevention. Based on the available data, antiplatelet agents should be used for patients with noncardioembolic stroke. The use of combination therapy (aspirin plus clopidogrel) has not been proven to be effective or safe to use for prevention of early stroke recurrence or in long-term treatment. There is no convincing evidence that any of the available antiplatelet agents are superior for a given stroke subtype. Currently, the uses of aspirin, clopidogrel, or aspirin combined with extended release dipyridamole are all valid alternatives after an ischemic stroke or transient ischemic attack. However, to maximize the effects of these agents, the treatment should be initiated as early as possible and be continued on a lifelong basis.     

Enhanced platelet activation by prolactin in patients with ischemic stroke

Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically. We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detected a significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors, 21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect, whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone.     

Secondary prevention in non-valvular atrial fibrillation patients: a practical approach with edoxaban

Patients with atrial fibrillation and prior stroke or transient ischemic attack exhibit a very high risk of recurrence. Secondary prevention with oral anticoagulants is mandatory. Overall, clinical guidelines recommend the use of target-specific oral anticoagulants over vitamin K antagonists for secondary prevention of stroke in patients with atrial fibrillation. However, many patients with atrial fibrillation and previous stroke are not receiving the appropriate antithrombotic treatment, perhaps due to the perceived risks of anticoagulation including the risk of hemorrhagic transformation of an ischemic stroke. The ENGAGE AF-TIMI 48 trial showed that although edoxaban 60 mg and warfarin reduced the risk of stroke to a similar extent, edoxaban exhibited a lesser risk of bleeding, particularly intracranial hemorrhage. Importantly, these data were independent of the presence of prior stroke or transient ischemic attack. Therefore, edoxaban can be used in both primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. The aim of this review was to update the available evidence about edoxaban in the clinical management of secondary prevention in individuals with non-valvular atrial fibrillation.     

Intracerebral haemorrhage,microbleeds and antithrombotic drugs

Antithrombotic therapy is a cornerstone for secondary prevention of ischaemic events, cerebral and extra-cerebral. A number of clinical questions remain unanswered concerning the impact of antithrombotic drugs on the risk of first-ever and recurrent macro or micro cerebral haemorrhages, raising the clinical dilemma on the risk/benefit balance of giving antiplatelets and anticoagulants in patients with potential high risk of brain bleeds. High field magnetic resonance imaging (MRI) blood-weighted sequences, including susceptibility weighted imaging (SWI), have expanded the spectrum of these clinical questions, because of their increasing sensitivity in detecting radiological markers of small vessel disease. This review will summarise the literature, focusing on four main clinical questions: how do cerebral microbleeds impact the risk of cerebrovascular events in healthy patients, in patients with previous ischaemic stroke or transient ischaemic attack, and in patients with intracerebral haemorrhage? Is the risk/benefit balance of oral anticoagulants shifted by the presence of microbleeds in patients with atrial fibrillation after recent ischaemic stroke or transient ischaemic attack? Should we restart antiplatelet drugs after symptomatic intracerebral haemorrhage or not? Are oral anticoagulants allowed in patients with a history of atrial fibrillation and previous intracerebral haemorrhage?     

Antiplatelet agents and randomized trials

Patients who have transient ischemic attack (TIA) or ischemic stroke are at a high risk of having a first or recurrent stroke. The annual risk is between 5% and 15%; the risk is highest in the first 48 hours following a TIA and highest in the first 7 days following an ischemic stroke. Secondary prevention includes antithrombotic therapy, treatment of risk factors, and interventional treatment of carotid stenosis. Antithrombotic options can include antiplatelet drugs such as aspirin, aspirin plus extended-release dipyridamole (ER-DP), clopidogrel, or clopidogrel plus aspirin. Oral anticoagulation is used in patients with a cardiac source of embolism such as atrial fibrillation. Aspirin monotherapy offers a modest risk reduction for recurrent stroke and for the combined endpoint of nonfatal stroke, myocardial infarction (MI), and vascular death. The combination of ER-DP and aspirin was shown to be superior to aspirin monotherapy in several trials. Clopidogrel is superior to aspirin in high-risk patients suffering from stroke, MI, or peripheral arterial disease. The combination of clopidogrel plus aspirin is not superior to aspirin or clopidogrel monotherapy and carries a significantly higher bleeding risk. The combination might offer benefit in short-term secondary prevention after TIA or stroke. Another ongoing trial is currently investigating the possible benefit and side effects of aspirin plus ER-DP versus clopidogrel in secondary stroke prevention.     

Stroke prevention in nonvalvular atrial fibrillation: a review of prospective randomized trials.

Patients with atrial fibrillation are at risk for cerebral embolism; however, the roles of chronic anticoagulation or antiplatelet therapy for stroke prevention in patients with nonvalvular atrial fibrillation have been controversial. Recently, the results of three large prospective randomized trials that examined the risks and benefits of warfarin or aspirin for stroke prophylaxis in patients with nonvalvular atrial fibrillation were reported. All three studies revealed a reduction in the stroke rate for patients treated with warfarin and a small incidence of major bleeding. One of the studies also reported a reduced stroke rate in aspirin-treated patients. The reduction of thromboembolic events associated with chronic warfarin therapy appears to outweigh the risks of significant bleeding for most patients with nonvalvular atrial fibrillation. Aspirin may offer an alternative for subgroups of patients who are at low risk for stroke or those who are not good candidates for anticoagulation.     

Warfarin for atrial fibrillation: the end of an era?

BACKGROUND: Warfarin has been in routine clinical use for more than 50 years; however, it was not proven to be of benefit in both primary and secondary prevention of stroke for patients with non-valvular atrial fibrillation (AF) until about a decade ago. Despite its efficacy in reducing the risk of stroke in patients with AF by about 60%, with an absolute reduction of about 3% per year, there have always been barriers to its use. These barriers have included the need for monitoring the degree of anticoagulation with blood tests to measure the international normalised ratio, frequent dose adjustments to maintain this ratio within quite a narrow therapeutic range, and the risk of bleeding should the upper limits of this range be exceeded. Aspirin has also been used but is less effective. RECENT DEVELOPMENTS: New oral drugs are being tested; these may be as effective at reducing stroke risk as warfarin in patients with AF. Direct thrombin inhibitors such as ximelagatran are not inferior to warfarin and, based on results from the SPORTIF III and V trials, are perhaps safer, with no need for long-term monitoring and dose adjustment. However, the side-effect of raised amounts of the liver enzyme alanine amino-transferase in 6% of patients needs to be resolved. In the ACTIVE trial, the efficacy of a combination of antiplatelet drugs (aspirin plus clopidogrel) is being tested against dose-adjusted warfarin; and in AMADEUS, the factor-Xa inhibitor and pentasaccharide idraparinux is being assessed in a similar way. Several surgical procedures and devices are also being developed to control AF rhythm and prevent stroke. WHERE NEXT?: The place of these new drugs in the management of AF needs to be established. In the short term, it seems that ximelagatran will replace warfarin in patients for whom there is evidence of a favourable risk-to-benefit ratio. The SPORTIF population consists of patients with AF plus at least one risk factor. More information about the effect of raised liver enzymes will probably not be available until phase IV studies are completed. Combination antiplatelet drugs need to be tested further--perhaps even triple therapy with aspirin, clopidogrel, and dipyridamole--if the results of ACTIVE are encouraging. The place of surgical procedures and devices to control rhythm and prevent stroke is unclear. Whatever happens, there is a high probability that the days of warfarin are numbered.     

Current oral antiplatelet agents to prevent atherothrombosis

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.     

低强度华法林在老年非瓣膜性心房颤动卒中高风险患者卒中一级预防中的疗效和安全性观察

目的   探讨低强度华法林在老年非瓣膜性心房颤动卒中高风险患者卒中一级预防中的疗效及安全性。 方法  本研究连续入组首都医科大学附属北京天坛医院2010年1月～2014年1月,心内科、老年科住院部及抗凝门诊确诊的治疗时间＞1年的非瓣膜性心房颤动卒中高风险患者80例,根据患者接受治疗情况分为低强度华法林治疗组和阿司匹林对照组各40例,其中华法林组控制凝血酶原时间国际标准化比值（international normalized ratio,INR）为1.6～2.5,比较两组患者缺血性卒中及全身大出血等不良反应的发生率。 结果  两组间在性别、年龄、伴随疾病等方面差异无显著性。低强度华法林治疗组心源性脑栓塞发生率为2.5%,阿司匹林治疗组为7.5%,两组比较差异无显著性（P＞0.05）。低强度华法林治疗组无其他部位栓塞发生,而阿司匹林治疗组患者其他部位栓塞仅1例,两组比较差异无显著性（P＞0.05）。两组均无心源性短暂性脑缺血发作发生。低强度华法林治疗组与阿司匹林治疗组均无严重脑出血、肾出血、其他器官出血等并发症发生。 结论  低强度华法林在非瓣膜性心房颤动卒中高风险患者卒中一级预防中疗效性与安全性方面可能与阿司匹林相当。     

Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials

BACKGROUND AND PURPOSE: Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. METHODS: We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. RESULTS: In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. CONCLUSIONS: The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.     

A Randomized trial comparing ticlopidine with aspirin fof the prevention of ischemic cerebral stroke

OBJECTIVE To assess the effect and cafety of t iclopidine in the prevention of ischemic cerebral stroke and to compare theeffect of low-dose aspirin with t iclopidine. BACKGROUND The effect and safety of ticlopidine irn the prevention of ischemic cerebral stroke in China has not been reported. METHODS 329 patients with TIA or mild ischemic cevebral stroke wasrandonmly assigned to ticlopidine group(165 case) or aspirin group (164 case) in this study.These patrents were randomly allocated to receive either 250mg trclopidine or 50mg aspirin daily and didnd take any other platelet antiaggregating drugs. Time of eacn follow up visit was one to two months. Follow up lasted for 6 to 18 months. RESULTS The event rate for stroke or death from any cause was 8.3% in ticlopidine group arid 14.9% in aspirin group. This repesented a risk reduction of 44.3%(95% cofidence interval, 0.29-0.94) for ticiopidine group as compared with aspirin group. The event raite for ischemic cerebral stroke or myocarction of ticlopidine group(7.0%)was lower than that cf aspirin group(14.8%)(P＜0.05).A riskreduction of 52.7%(95% confidence interval,0.24-0.92) for ticlopidine group compared with aspirin group. The rate of adverse effects of ticlopidine group and aspirin group were 6.9% and 11.0% during the trial ,but this was not statistically significant(P＜0.05).DISCUSSION and CONCLUSION Therapeutic efficacy for the prevention oi ischemic stroke of ticlopidine was better than that of aspirin, the rate of side effects in ticlopidine group and aspirin group are not statistically significant. So ticiopidine could serve as a first-line drug for the prevention of ischemic stroke.     

Antiplatelet therapy in ischemic stroke

Stroke is the third leading cause of death and the leading cause of disability in the developed world. Atherothrombosis is the underlying condition that results in events leading to ischemic stroke and vascular death. Antiplatelet therapy is commonly used for both acute stroke and in secondary prevention. Numerous trials and meta-analyses have left little doubt that antiplatelet therapy effectively reduces stroke risk in patients with prior stroke or transient ischemic attack. Current antiplatelet agents include acetylsalicylic acid, clopidogrel, ticlopidine and extended release dipyridamole with low doses of acetylsalicyclic acid (aspirin). The optimum doses of antiplatelet drugs depend upon several variables, such as genetic and environmental factors, so that clinical and laboratory response for dosage varies for each patient. Recently, the correlation between the laboratory-measurable effect of antiplatelet agents and the clinical effectiveness on the mortality of ischemic stroke and cardiovascular patients has been documented. Due to the side effect of bleeding with different antithrombotic drugs, their future employment will be determined in combination with low dosages of each component. Laboratory-controlled, tailored drug therapy will be needed for long-lasting secondary prevention of ischemic stroke.     

Role of ticlopidine for prevention of stroke.

BACKGROUND: Ticlopidine, an antiplatelet agent with a unique mechanism of action, is now available for clinical use in the United States and Canada. SUMMARY OF COMMENT: Recently two large randomized trials demonstrated that ticlopidine can reduce the risk of subsequent stroke in patients presenting with a transient ischemic attack or stroke. One study found that ticlopidine was more effective than aspirin for stroke prevention; however, it was less well tolerated than aspirin and was associated with severe but reversible neutropenia in almost 1% of patients. CONCLUSIONS: Ticlopidine is effective for both primary and secondary stroke prevention. It has a favorable risk/benefit ratio and is a particularly attractive option for patients who are unable to take aspirin.