Ischemic stroke prevention: an update on antiplatelet therapy

Stroke is the third leading cause of mortality in the United States. As the leading cause of neurological deficits worldwide, stroke is associated with tremendous costs both to society and to the individuals and families stroke impacts. Antiplatelet agents have demonstrated efficacy in preventing recurrent atherothrombotic strokes and are the principal pharmacologic modality employed. With the recent development of the thienopyridines and the resurgence of dipyridamole, recommendations for antiplatelet therapy have undergone several iterations over the past decade. The focus of this review is to provide an update on the individual antiplatelet agents and recapitulate the current guidelines for antiplatelet selection and use in either transient ischemic attack or noncardiogenic ischemic stroke patients. Mechanisms of action, demonstrated efficacy, adverse effect profiles, and current consensus recommendations are reviewed for four conventional antiplatelet strategies, aspirin, ticlopidine, clopidogrel, and the combination of aspirin and extended-release dipyridamole.     

Ischemic stroke prevention: An update on antiplatelet therapy

Abstract

Stroke is the third leading cause of mortality in the United States. As the leading cause of neurological deficits worldwide, stroke is associated with tremendous costs both to society and to the individuals and families stroke impacts. Antiplatelet agents have demonstrated efficacy in preventing recurrent atherothrombotic strokes and are the principal pharmacologic modality employed. With the recent development of the thienopyridines and the resurgence of dipyridamole, recommendations for antiplatelet therapy have undergone several iterations over the past decade. The focus of this review is to provide an update on the individual antiplatelet agents and recapitulate the current guidelines for antiplatelet selection and use in either transient ischemic attack or noncardiogenic ischemic stroke patients. Mechanisms of action, demonstrated efficacy, adverse effect profiles, and current consensus recommendations are reviewed for four conventional antiplatelet strategies, aspirin, ticlopidine, clopidogrel, and the combination of aspirin and extended-release dipyridamole. [Neurol Res 2002; 24: 381-388]     

European stroke prevention study: effectiveness of antiplatelet therapy in diabetic patients in secondary prevention of stroke.

BACKGROUND AND PURPOSE: The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid three times a day with the effect of a placebo in the prevention of stroke or death in 1,861 patients after one or more episodes of recent transient ischemic attack or cerebral infarction. METHODS: The present study represents a secondary analysis of the efficacy of study medication in diabetic (n = 216) and nondiabetic (n = 1,645) patients. RESULTS: The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects. CONCLUSIONS: The combination of dipyridamole and acetylsalicylic acid appeared to be more effective in nondiabetic subjects than in diabetic subjects in the prevention of death and stroke although the low number of diabetic patients may at least in part explain this result.     

Current issues in antiplatelet therapy for stroke prevention: the importance of stroke subtypes and differences between stroke and MI patients

Ischaemic stroke, the most common type of stroke, is classified into three main subtypes: large-vessel disease, lacunar or small-vessel disease, and cardioembolic; two further subtypes include a determined aetiology of “other” and cryptogenic. Although a substantial amount of literature exists concerning current guidelines for the secondary prevention of ischaemic stroke, treatment strategies for stroke subtypes as well as the reasons why these subtypes are significant have yet to be clearly defined. Furthermore, treatment strategies for secondary prevention of ischaemic stroke differ between patients who have suffered a previous stroke and those who have suffered a myocardial infarction. Antiplatelet therapies offer treatment that is as efficacious as warfarin, but with less severe bleeding. This review examines the importance of the different subtypes of stroke as well as differentiating between treating a heart patient and a stroke patient for secondary stroke prevention, including the advantages of using antiplatelet therapy over anticoagulants.     

Recent clinical trial results with antiplatelet therapy: implications in stroke prevention

Dual antiplatelet therapy that inhibits more than one pathway of platelet activation is appealing and biologically rational. The CURE study evaluated the efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus standard therapy (including ASA) in over 12,000 patients with unstable angina or non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination with ASA reduced the relative risk of the combined atherothrombotic endpoint of cardiovascular death, MI or stroke by 20% (95% CI 0.72-0.90; p < 0.001) and the absolute risk of this composite endpoint by 2.1%. While the study was not powered or designed to demonstrate a reduction in stroke, there was a 14% reduction in stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI-CURE, a prespecified substudy of patients who underwent percutaneous coronary intervention (PCI) during CURE, confirmed the early and sustained benefits of clopidogrel therapy seen in the overall CURE study. CREDO was a randomized, double-blind, placebo-controlled trial in more than 2,100 patients that evaluated the continuation of clopidogrel on top of standard therapy including ASA for 12 months after PCI, and the benefit of a preprocedural clopidogrel loading dose. The long-term results at 1 year showed that there was a 27% reduction in the risk of stroke, MI or death with long-term clopidogrel therapy (p = 0.02). There was a consistent benefit of extended clopidogrel therapy for each component of the composite endpoint, with a 25.1% relative risk reduction for all-cause stroke. In patients who received clopidogrel > or =6 h before PCI, there was a 39% reduction in the risk of death, MI or urgent target-vessel revascularization at 28 days (p = 0.051). These data suggest important implications in the future for the use of an early loading dose of clopidogrel in patients undergoing carotid stenting and, if proven in current or future trials, the use of a loading dose followed by long-term continuation of clopidogrel in other high-risk atherothrombotic patients such as those with transient ischaemic attack or ischaemic stroke.     

长期服用抗血小板药物对急性缺血性脑血管病严重性的影响

本文以临床计分，ＣＴ梗塞灶和血小板胞浆钙离子为指标，对２３例发病前长期服用抗血小板药物（服药组）和２２例未服用抗血小板药物（对照组）的急性缺血性脑血管病患者进行了对照研究，结果发现服药组的临床特点，梗塞灶的大小及血小板胞浆游离钙离子升高的程度都明显轻于对照组。我们认为有缺血性脑血管病危险因素的老年人，适量服用阿斯匹林是有益的。     

Discontinuation of perioperative antiplatelet and anticoagulant therapy in stroke patients

Growing evidence suggests that perioperative withdrawal of ASA for secondary stroke prevention increases thromboembolic risk without the associated benefit of decreased bleeding complications. ASA maintenance is acceptable in many procedures, including invasive ones. Many procedures, in particular ophthalmologic, dermatologic, and dental surgeries, also are safe while continuing oral AC. Warfarin has been continued successfully even in some surgeries that have high bleeding risk. When the risk is too high, temporary bridging therapy with LWMH is safe in many populations. Although the exact thromboembolic risks associated with temporary cessation of AP and AC are unknown and likely low, morbidity and mortality associated with thromboembolism are high. Further studies investigating the risks and benefits of maintaining AP and AC during procedures, particularly invasive ones, are needed. Meanwhile, it is critical that physicians understand the risks and benefits of perioperative AP and AC and the variety of procedures in which these agents can be safely continued.     

Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke

Antiplatelet agents are essential in treating patients with acute ischaemic stroke (AIS) to prevent recurrent ischaemic events. The aim of this study was to evaluate the effectiveness of early antiplatelet therapy with different aspirin (ASA) dosages in patients with AIS. This observational study included 454 patients with AIS in whom antiplatelet treatment was initiated. The antiplatelet effect was determined by whole blood aggregometry within 48 hours after antplatelet therapy was initiated. An impedance change exceeding 0 W after stimulation with arachidonic acid was defined as ASA low response (ALR) and ≥5 Ω in ADP-stimulated specimen as clopidogrel LR. Of the study group 53.5% patients were treated with 200 mg ASA orally, 27.5% with 500 mg ASA intravenously, 8.6% with 100 mg ASA orally, and 7.7% with 75 mg clopidogrel. A dose-dependent antiplatelet effect of ASA treatment was found: 18.4% of patients with 500 mg ASA intravenously were ALR, in contrast to 32.5% on 200 mg and 35.9% on 100 mg ASA orally. Clopidogrel treatment without a loading dose resulted in a high proportion of LR (45.7%). Using the propensity score method revealed a three times higher risk for ALR for patients treated with ASA 200 mg [odds ratio 2.99 (1.55-5.79)] compared to treatment with ASA 500 mg. In conclusion, initiating antiplatelet therapy in patients with AIS resulted in a dose-dependent insufficient platelet inhibitory effect. Our findings suggest using a loading dose of 500 mg ASA intravenously as this seems to be favourable when a sufficient early platelet inhibitory effect is wanted.     

雌孕激素联合补充治疗与脑卒中的预防

目的　探讨低剂量雌孕激素联合补充治疗对脑卒中的预防作用。方法　绝经过渡期及绝经后妇女84例随机设激素补充治疗组和对照组 ,采用酶免法测定治疗前后血脂和雌二醇 (E2 )水平。结果　治疗前后 E2、高密度脂蛋白 (HDL)增高 ,低密度脂蛋白 (L DL)、总胆固醇 (TC)降低 ,差异显著 (P<0 .0 5 ) ,甘油三酯 (TG)变化不明显。结论　低剂量雌激素对血脂谱产生有利影响 ,可降低脑卒中的发生     

Biological basis for statin therapy in stroke prevention

Hypercholesterolemia has not been considered an important risk factor for stroke; however, statin therapy reduces stroke in coronary heart disease patients. Statins may provide cerebrovascular protection through various mechanisms that include a reduction in the incidence of embolic stroke from cardiac, aortic and carotid sites, stabilization of vulnerable carotid atherosclerotic plaque, and improvement in cerebral blood flow.     

Secondary prevention of stroke with antiplatelet agents in patients with diabetes mellitus

The prevalence of diabetes mellitus (DM) varies from 1.2 to 13.3% in the general population. The most frequent is type 2 (non-insulin-dependent) DM, which constitutes 90-95% of all cases. DM increases the risk of cardiac disease, stroke, retinopathy, nephropathy, neuropathy and gangrene, and the disease is associated with an increased prevalence of other cardiovascular risk factors such as hypertension, hypercholesterolaemia, asymptomatic carotid artery disease, and obesity. The risk of stroke may be directly and indirectly increased by the presence of DM. Epidemiological data show that DM independently amplifies the risk of ischaemic stroke from 1.8- up to 6-fold, so that prevention of cardiovascular risk in diabetics is of utmost importance. The main goal is to control glycaemia, although it has never been shown to be beneficial in stroke patients. Other preventive strategies include antiplatelet treatment. The open-label Primary Prevention Project trial tested the efficacy of low-dose acetylsalicylic acid (ASA) in prevention of ischaemic events in high-risk patients, but failed to demonstrate a significant benefit of ASA in diabetic patients. However, in the CAPRIE trial, the benefit of clopidogrel was amplified in patients with DM versus those without DM in preventing ischaemic events. This difference was even more striking when comparing patients treated with insulin versus non-diabetics. Another trial -- MATCH -- tested the benefit of adding ASA to clopidogrel versus clopidogrel alone in the prevention of ischaemic events in high-risk cerebrovascular patients, two-thirds of whom had DM. Further research is needed to clarify the effects of different antiplatelet regimens in stroke prevention in diabetic patients, who should be considered as high vascular-risk patients.     

双联抗血小板治疗非心源性缺血性脑卒中的有效性及安全性

目的探讨双联抗血小板治疗非心源性缺血性脑卒中的临床疗效和安全性。方法选取我院就诊的非心源性缺血性脑卒中患者150例,随机分为2组,每组75例。2组均给予相同的基础治疗以及强化他汀类药物治疗,在此基础上,试验组于入院当日口服拜阿司匹林300mg,硫酸氢氯吡格雷300mg,第2天开始每日口服拜阿司匹林100mg,硫酸氢氯吡格雷75mg;对照组于入院当天口服拜阿司匹林300mg,第2天开始改为每日口服拜阿司匹林100mg。治疗4周后,观察比较2组的治疗效果、实验室指标、不良反应发生率、复发率情况。结果试验组总有效率85.33%,对照组为65.33%,差异有统计学意义(P0.05);试验组血小板聚集率、血浆黏度、全血低切黏度明显低于对照组;2组不良反应发生率无明显差异(P0.05);试验组2例复发,复发率为2.67%,对照组10例复发,复发率13.33%,试验组复发率低于对照组(P0.05)。结论双联抗血小板治疗非心源性脑卒中临床疗效满意,复发率较低,且无明显不良反应,安全性良好。