Aspirin non-responder status in patients with recurrent cerebral ischemic attacks

Background: Antiplatelet agents such as acetylsalicylic acid (aspirin) reduce the relative risk for cerebrovascular events in patients with cardiovascular or cerebrovascular disorders by approximately 23 %. Recent observations raise the possibility that aspirin resistance may contribute to the failure of aspirin treatment in a significant proportion of patients (aspirin non-responders). To evaluate the clinical relevance of aspirin non-responder status, we analysed platelet functions in symptomatic and asymptomatic patients treated with aspirin for secondary prevention of cardiovascular and cerebrovascular events. Methods: A total of 53 patients on 100 mg aspirin daily for secondary prevention (mean treatment duration > 60 months) were included. Patients were categorized as asymptomatic if they were free of cerebrovascular incidents for at least 24 months (n = 18). Symptomatic patients had suffered ischemic strokes or transient ischemic attacks within the previous 3 days (n = 35). Platelet function was assessed using the PFA–100 system that allows for quantitative assessment of platelet function, reporting platelet aggregatability as the time required to close a small aperture in a biologically active membrane. Results: Collagen/epinephrine closure times were significantly shorter in symptomatic patients than in asymptomatic patients (p < 0.01). Individual closing times were normal in 12 of 35 symptomatic patients (34 % non-responders) whereas all asymptomatic patients had prolonged closure times. Conclusions: Aspirin non-responder status may contribute to failure of aspirin therapy in the secondary prevention of cerebrovascular incidents in as much as 30–40 % of patients. Quantitative assessment of platelet functions may provide a means to predict aspirin treatment failure in individual patients and to re-direct therapeutic strategies. Received: 7 May 2002, Received in revised form: 28 August 2002, Accepted: 2 September 2002 Correspondence to Priv.-Doz. Dr. Helge Topka     

Addition of cilostazol reduces biological aspirin resistance in aspirin users with ischaemic stroke: a double‐blind randomized clinical trial

Background and purpose: Biological aspirin resistance (AR) has been recognized as an important cause of clinical AR. Recent studies have reported the beneficial effects of cilostazol for the prevention of cardiovascular diseases. This study investigated whether addition of cilostazol to aspirin in ischaemic stroke patients can reduce AR. Methods: In this double‐blind multicenter trial, 244 aspirin users with ischaemic stroke were randomly assigned to receive cilostazol 100 mg twice daily or to placebo. Antiplatelet function was assessed using the VerifyNow? Aspirin system. The primary end‐point was the incidence of AR, which was measured as aspirin resistance unit (ARU) ≥550 after 4‐week treatment. Results: The incidence of AR after treatment in cilostazol group was not significantly different from that in placebo (8.8% vs. 10.9%, P = 0.578). However, AR decreased from 12.8% to 8.8% in cilostazol group, whereas it was not changed in the placebo group. The mean ARU after treatment were also lower in the cilostazol group (456.9 ± 56.0 vs. 470.7 ± 67.2, P = 0.081). Cilostazol addition did not prolong bleeding time. Conclusions: Although this was a negative study, our findings disclosed a trend toward enhanced antiplatelet effects when cilostazol was added to aspirin in ischaemic stroke patients. Combination of aspirin and cilostazol might be a treatment option in the ischaemic stroke patients with AR.     

Effect of cilostazol on cerebral arteries in secondary prevention of ischemic stroke

Objective

To compare the effects of cilostazol on cerebral arteries and cerebrovascular blood flow in secondary prevention of ischemic stroke, with those of aspirin.

Methods

Sixty-eight patients who had ischemic stroke during the recent 1–6 months were recruited and randomized into cilostazol or aspirin group. Cerebrovascular condition was assessed by magnetic resonance angiography (MRA) and transcranial doppler ultrasonography (TCD) at the beginning of the study and after 12-month medication.

Results

During the clinical follow-up, ischemic stroke recurred in 2 patients in cilostazol group, while in aspirin group, one case of ischemic stroke recurrence and one case of acute myocardial infarction were found. MRA revealed that in aspirin group, the percentages of patients experiencing aggravation and attenuation of cerebrovascular condition were 3.3% and 6.7%, respectively, while in aspirin group, they were 3.3% and 10%, respectively. Moreover, TCD revealed that 26.9% of the patients in aspirin group and 14.3% of the patients in cilostazol group experienced aggravation of cerebrovascular condition. However, the systolic peak flow velocity of the previously abnormal arteries increased by 42.9% after 12-month medication of cilostazol, which was significantly higher than that after aspirin medication (27.5%) (P = 0.04). Furthermore, as a major side effect of antiplatelet therapy, the frequrency of bleeding was much less in cilostazol group (0 case in cilostazol group vs 5 in aspirin, P < 0.05).

Conclusion

Cilostazol is as effective as aspirin in preventing the aggravation of cerebral arteries in secondary prevention of ischemic stroke. Besides, it is more safe. Cilostazol can increase the systolic peak flow velocity of cerebral arteries, which may improve the blood supply of focal ischemia.     

The effect of aspirin, ticlopidine and their low-dose combination on platelet aggregability in acute ischemic stroke: a short duration follow-up study

We investigated the effects of aspirin (300 mg/d), ticlopidine (500 mg/d) and their low-dose combination (aspirin 100 mg/d plus ticlopidine 250 mg/d) on the platelet aggregability using the Wu and Hoak method. Each treatment group consisted of 25 patients with acute ischemic stroke. Platelet aggregation ratios (PAR) were measured on the 1(st) (before treatment), 10(th) and 90(th) days in the treatment groups and compared with those of 25 control cases. On the first day, comparison of PAR in each treatment group with the control was significant, while the differences between treatment groups were not significant. On the 90(th) day, differences of PAR between aspirin and control were significant, but differences between the other treatment groups and the control group were not significant, indicating a lower anti-aggregant efficacy of aspirin. Our study suggests that PAR determination can be used to assess the efficacy of anti-aggregant drugs. Our crude observation also suggests a higher anti-aggregant efficacy of ticlopidine, and aspirin plus ticlopidine, than aspirin. In addition, proper doses of aspirin plus ticlopidine may be a good choice for the prevention of ischemic stroke. Further studies are required to assess whether PAR determination could be useful for assessing patients at risk of stroke, and for drug selection for the prevention of stroke.     

High-on-Aspirin Platelet Reactivity Differs Between Recurrent Ischemic Stroke Associated With Extracranial and Intracranial Atherosclerosis

Background and PurposeIschemic stroke recurs despite the use of antiplatelet agents. Various mechanisms are involved in recurrence due to intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS). High-on-aspirin platelet reactivity (HAPR) may differ between recurrent stroke due to ICAS and ECAS.MethodsPatients with recurrent ischemic stroke as a result of large-artery atherosclerosis despite taking aspirin were enrolled consecutively. Ischemic stroke was classified as stroke due to ICAS or ECAS according to the location of the culprit stenosis. An aspirin reaction units (ARU) value of >550 IU was defined as HAPR. HAPR and its associated factors were compared between the two groups and also considering the mechanism of stroke.ResultsAmong the 190 patients with recurrent stroke (111 with ICAS and 79 with ECAS), 36 (18.3%) showed HAPR. The ARU value was higher in the ECAS than the ICAS group (492±83 vs. 465±78, mean±standard deviation; p=0.028), as was the proportion of patients with HAPR (27.8% vs. 12.6%, p=0.008). Being male and having stroke due to ECAS (reference=stroke due to ICAS: odds ratio=5.760; 95% confidence interval=2.154–15.403; p<0.001) was independently associated with HAPR. The ARU value differed according to the stroke mechanism, and was highest in those with artery-to-artery embolism. Artery-to-artery embolism was independently associated with HAPR in both the ICAS and ECAS groups.ConclusionsRecurrent stroke due to ECAS was more strongly associated with HAPR and insufficient antiplatelet inhibition than was that due to ICAS. Artery-to-artery embolism was associated with HAPR in recurrent ischemic stroke as a result of ICAS or ECAS.     

Ex vivo response to aspirin differs in stroke patients with single or recurrent events: a pilot study

The dose of aspirin for secondary stroke prevention and the clinical meaning of ex vivo platelet abnormalities are debated. We assessed prospectively 39 noncardioembolic stroke patients in which 300 mg/day aspirin had proved effective (n=24) or ineffective (n=15) to prevent recurrent ischemic events. We evaluated platelet aggregation induced by arachidonic acid, adenosine diphosphate and epinephrine, and the sensitivity of platelets to increasing concentrations of the synthetic thromboxane mimetic U46619. Aggregation studies were repeated while subjects received 300 (study phase 1), and 600 (study phase 2) mg/day aspirin, respectively. Overall, arachidonic acid-induced platelet aggregation was less effectively inhibited during study phase 1 compared to phase 2. Arachidonic acid and epinephrine promoted a stronger platelet aggregation in aspirin nonresponders than in aspirin responders while taking 300 mg/day aspirin. On the other hand, 600 mg/day effectively inhibited platelet function in both clinical groups. A lower sensitivity to thromboxane receptors was also found during phase 1 of the study, although the response was similar between aspirin responders and nonresponders. This pilot study suggests that 300 mg/day aspirin is less effective than 600 mg/day to block the cyclooxygenase pathway in noncardioembolic stroke and, incomplete cyclooxygenase inhibition is associated with recurrent thromboembolic events despite adequate aspirin compliance. It is likely that patients could receive a more efficacious stroke prevention if the dose of aspirin is tailored to individual needs as reflected by laboratory findings.     

ADP‐induced platelet aggregation in acute ischemic stroke patients on aspirin therapy

Background and purpose: Aspirin is an important therapeutic regimen to prevent the recurrent ischemic events or death after acute ischemic stroke. In this study, we evaluated the relationship between the extent of adenosine diphosphate (ADP) ‐induced platelet aggregation and outcome in acute ischemic stroke patients on aspirin therapy. Methods: We selected 107 acute ischemic stroke patients who had been prescribed aspirin and evaluated platelet function test by using optic platelet aggregometer test after 5 days of taking it and investigated the prognosis 90 days after ischemic events. Kaplan–Meyer curve was used for survival analysis. Results: After stratification of the subjected patients by tertiles of ADP‐induced platelet aggregation, the events rates were 7.4%, 9.3% and 30.8% (P = 0.023). In multiple logistic regression analysis, old age over 70 years (OR, 13.7; 95% CI, 2.14–88.07; P = 0.001) and the increased ADP‐induced platelet aggregation had independent significance to the risk of primary end‐points after acute ischemic stroke (OR, 1.1; 95% CI 1.01 to 1.20; P = 0.026). Conclusions: This study showed that the increased ADP‐induced platelet aggregation under using aspirin is associated with poor outcome after acute ischemic stroke.     

Clinical consequences of aspirin and clopidogrel resistance: an overview

The aim of this review is to introduce the concept of personalized medicine in secondary stroke prevention with antiplatelet medication. In the last years, many studies have been conducted regarding aspirin resistance and genotyping of clopidogrel metabolism. A review of the currently published data on this issue emphasizes the importance of focusing on the individualizing approach in antiplatelet therapy to achieve maximal therapeutic beneficial effect. However, many authors suggest that, before new information from ongoing trials become available, good clinical practice should dictate the use of low dose of aspirin that was shown to be effective in the prevention of stroke and death in patients with ischemic cerebrovascular disease, because higher doses do not have significantly better efficacy than lower doses in secondary stroke prevention, but lower‐dose aspirin is associated with less side effects. On the other hand, many factors are associated with clopidogrel resistance, and recent genetic studies showed that the CYP2C19*2 genotype (loss‐of‐function allele) is related to poor metabolism of clopidogrel, but larger studies are needed to definitively confirm or rule out the clinical significance of this genetic effect. The aim of personalized approach in secondary stroke prevention is to take the most appropriate medicine in the right dose in accordance with the clinical condition of the patient and associated risk factors.     

Can aspirin resistance be clinically predicted in stroke patients?

OBJECTIVES: Aspirin resistance is one of several possible explanations for limited efficacy or treatment failure of aspirin. However, the predictors of aspirin resistance are not well known. We therefore conducted a study of laboratory-defined aspirin resistance in Korean patients with ischemic stroke and considered a wide range of factors as possible predictors. PATIENTS AND METHODS: A total of 88 patients taking aspirin daily for the secondary prevention of stroke were included. Platelet function was assessed using the Rapid Platelet Function Assay-Aspirin (RPFA-ASA) system and the level of urinary thromboxane B2 (TX-B2). The result of the RPFA-ASA system was expressed as an aspirin reaction unit (ARU). We analyzed a wide range of factors including demographic data, stroke risk factors, and laboratory findings to identify the clinical predictors of aspirin resistance. RESULTS: Eleven (12%) patients were identified as aspirin resistant by the ARU criteria. Univariate analysis showed that an older age, lower LDL cholesterol levels, and concurrent use of angiotensin converting enzyme inhibitors or receptor blockers were related to aspirin resistance by ARU criteria. Aspirin resistance by urinary TX-B2 criteria was observed in 18 (25%) patients and associated with an older age, metabolic syndrome, diabetes, cigarette smoking, and the use of angiotensin-converting enzyme inhibitors or receptor blockers. In multivariate analysis, this association lost significance by ARU criteria, and only lower fibrinogen levels were associated with increased risk by TX-B2 criteria. In addition, the stroke subtypes and the degree of atherosclerosis were not associated with aspirin resistance. The correlation between the two criteria was poor (r=-0.115, p=0.34). CONCLUSION: Despite the comprehensive analysis of this study, we failed to identify independent predictors for laboratory-defined aspirin resistance. Additionally, little overlap was found between the two criteria with which to assess aspirin resistance.     

Adherence to aspirin in secondary prevention of ischemic stroke

OBJECTIVE: Compliance with antiplatelet therapy is essential for the efficiency of secondary prevention of ischemic stroke. The objective of this study was to evaluate adherence to aspirin treatment in patients with ischemic stroke. PATIENTS AND METHODS: We studied outpatients of 5 neurological ambulatory centers in an urban city, Valencia, all with a history of ischemic stroke who had received aspirin for at least 6 months. A personal interview was carried out in all cases, during which the patients were questioned about adherence to treatment. Platelet thromboxane A2 synthesis was assessed in a single laboratory for the biochemical determination in all patients. RESULTS: A total of 73 patients (mean age 67) were studied, with a mean duration of aspirin therapy of 25.4 months (range 6-144 months). Sixty-six patients (90.4%) were included in laboratory tests. All showed inhibition of thromboxane A2 synthesis, consistent with adherence to treatment. CONCLUSIONS: Aspirin compliance was found to be excellent. All the patients who presented themselves for laboratory tests were taking aspirin. Even if the patients who failed to show up for laboratory testing are regarded as noncompliants, at least 90% of all patients were compliants--in agreement with the findings of the recent literature. Personal interview plus biochemical determination of platelet thromboxane A2 synthesis seem adequate for assessing adherence to aspirin.     

血小板功能实验预测氯吡格雷用于缺血性卒中二级预防的有效性和安全性分析

目的 探讨透射光法血小板聚集实验(light transmittance aggregometry,LTA)、血栓弹力图(thromboelastography,TEG)和血小板功能分析仪(platelet function analyzer,PFA)三种血小板功能实验对轻型缺血性卒中患者临床结局的预测价值.方法 前瞻...     

通心络与阿司匹林预防再次缺血性脑卒中的作用

目的观察通心络胶囊在预防再次缺血性脑卒中的作用，并与阿司匹林对比。方法将128例急性脑梗死患者随机分为两组：通心络胶囊组62例，阿司匹林组66例，观察两组患者服药期间缺血性卒中的再发生、死亡及不良反应等临床表现。结果两组比较缺血性脑卒中的人数分别为通心络组6例，阿司匹林组8例，虽然通心络组比阿司匹林组发生人数少，但两组比较无统计学差异（P〉0．05）。两组不良反应比较通心络组为4例，阿司匹林组12例，差异有统计学意义（P〈0．05）。结论通心络胶囊预防再次缺血性脑卒中与阿司匹林有同样的作用，但阿司匹林组有较多的不良反应。     

The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism is also associated with the risk of clinical thrombotic events in patients using aspirin. We included 496 patients admitted to our Coronary Care Unit for various indications treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that patients with the common genotype more frequently used aspirin prior to admission compared to those patients with the variant genotype. The composite primary endpoint of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular death in 12.1%. The unadjusted hazard ratio (95% CI) for the primary endpoint for patients with the variant versus the common genotype was 1.07 (0.62-1.85), p = 0.8. The adjusted hazard ratio was 0.86 (0.49-1.50), p = 0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane production and platelet function. However, in this cohort of patients using low-dose aspirin for secondary prevention the polymorphism was not associated with a higher risk of atherothrombotic events.     

个体化抗血小板治疗对缺血性卒中二级预防的效果研究

目的 研究个体化抗血小板治疗在缺血性卒中二级预防的效果。 方法 选择2013年3月-2014年5月于陕西省人民医院就诊的急性缺血性卒中患者207例,随机分为 常规治疗组与个体化治疗组。常规治疗组应用阿司匹林100 mg/d抗血小板治疗。个体化治疗组应用 Essen卒中风险评分量表（Essen Stroke Risk Score,ESRS）将高危组给予氯吡格雷75 mg/d,低危组给 予阿司匹林100 mg/d抗血小板治疗。7 d后进行血栓弹力图（thromboela stogram,TEG）及CYP2C19基因型 检测,结合TEG及CYP2C19基因型结果,决定抗血小板治疗方案。随访1年,比较个体化治疗组和常规 治疗组患者终点事件发生率。 结果 CYP2C19快代谢基因型、中间代谢基因型患者应用氯吡格雷的血小板抑制率明显高于慢代谢 型,结果差异有显著性（P =0.018,P =0.015）。个体化治疗组（112例）和常规治疗组组（95例）终点事 件发生率差异无显著性（P＞0.01）。 结论 CYP2C19快代谢基因型、中间代谢基因型患者应用氯吡格雷的血小板抑制率明显高于慢代谢 型。与阿司匹林常规治疗方案相比,利用CYP2C19基因多态性与TEG检测指导下的个体化抗血小板方 案未显示降低缺血性卒中后终点事件发生率,可能需要更大规模、随访时间更长的研究。     

Resistance to aspirin in vitro at rest and during exercise in patients with angiographically proven coronary artery disease

BACKGROUND: Acetylsalicylic acid, or aspirin, is widely used in secondary prevention of coronary artery diseases, but the inhibition of platelet aggregation is not uniform in all individuals. OBJECTIVE: To investigate the prevalence of aspirin resistance at rest and during exercise in coronary artery disease patients. MATERIALS AND METHODS: Fifty patients with stable coronary artery disease were prospectively studied. All patients received aspirin (75-300 mg/day for >1 month) and no other antiplatelet therapy. Aspirin resistance was studied, at rest and immediately after a stress test, using the standardized platelet function analyzer (PFA-100(R), Dade-Behring). Aspirin resistance was defined as a normal collagen/epinephrine closure time (<186 s). RESULTS: Ten patients (20%) were aspirin-resistant at rest. Out of the 40 patients who were aspirin-sensitive at rest, 9 (22%) were aspirin-resistant immediately after the exercise stress test. There were no differences in aspirin sensitivity regarding gender, age, diabetes, hypertension, dyslipidemia, platelet count, medical treatment or number of the coronary arteries involved. CONCLUSIONS: Aspirin resistance is detected, at rest, in 20% of our patients with stable coronary artery disease. Aspirin treatment does not seem to protect against exercise-induced platelet activation in 22% of such patients, despite aspirin sensitivity at rest.     

阿司匹林间歇疗法在脑卒中二级预防中的临床价值

目的观察阿司匹林间歇疗法与常规疗法在脑卒中二级预防中临床价值的差异。方法收集250例脑卒中恢复期患者,按随机单盲开放对照原则分为间歇疗法组(间歇组)(每8周内停药1周)和常规疗法组(单规组)各125例,均给予阿司匹林100mg Qd治疗2年。结果(1)2组脑卒中再发率无明显差异;(2)2组患者的血小板聚集率和凝血功能无明显差异;(3)间歇组上消化道出血、腹痛、腹泻等不良反应发生率较常规组明显下降(P<0.01)。结论阿司匹林间歇疗法较常规疗法能有效减低了长期治疗导致的消化道不良反应,同时有效降低脑卒中的再发率,在脑卒中二级预防中具有重要的临床应用价值。     

Intravenous thrombolysis versus antiplatelet therapy in minor stroke patients with large vessel occlusion

Aim

Our study aimed to explore the effectiveness and safety of intravenous t-PA compared with dual antiplatelet therapy (DAPT) and aspirin alone for minor stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤5 and large vessel occlusion (LVO).

Methods

Patients with minor stroke harboring LVO within 4.5-h time window were included from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018 in China. Clinical outcomes including modified Rankin scale (mRS) score, recurrent stroke, and all-cause mortality at 90 days and 36-h symptomatic intracerebral hemorrhage (sICH) were collected. Multivariable logistic regression models and propensity score matching analyses were used to determine the association between treatment groups and clinical outcomes.

Results

A total of 1401 minor stroke patients with LVO were included. Overall 251 patients (17.9%) received intravenous t-PA, 722 patients (51.5%) received DAPT, and 428 patients (30.5%) received aspirin alone. The intravenous t-PA was associated with greater proportions of mRS 0–1 (aspirin versus t-PA: adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.32 to 0.80; p = 0.004; DAPT versus t-PA: aOR, 0.76; 95% CI, 0.49 to 1.19; p = 0.23). Using propensity score matching analyses, the results were similar. There was no difference in 90-day recurrent stroke among the groups. The rates of all-cause mortality in intravenous t-PA, DAPT, and aspirin groups were 0%, 0.55%, 2.34%, respectively. No patient developed sICH within 36 h of intravenous t-PA.

Conclusion

In patients with minor stroke harboring LVO within 4.5-h time window, intravenous t-PA was associated with higher odds for the excellent functional outcome, as compared with the aspirin alone. Further randomized controlled trials are warranted.     

中成药对缺血性脑血管病二级预防疗效随访观察

目的 探讨中成药对缺血性脑血管病二级预防的疗效.方法 2008-12～2009-08在潍坊市脑科医院神经内科门诊及住院诊断为缺血性脑血管病的患者,其中服用阿司匹林127例作为对照组,在常规服用阿司匹林基础上加用中成药119例作为治疗组,电话及门诊随访6~12个月,比较2组患者脑梗死复发率.结果 治疗组的复发率为10.9...     

Aspirin failure in patients presenting with acute cerebrovascular ischaemia

Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10-15%) persisted in 11 subjects - suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention.     

Danish very-low-dose aspirin after carotid endarterectomy trial

The effect of very-low-dose aspirin as an antithrombotic agent was evaluated blindly in 301 patients who had recently undergone carotid endarterectomy. After randomization, 150 patients received aspirin and 151 received placebo. The two groups were comparable with regard to age, sex, blood pressure, previous cerebrovascular events, and smoking habits. The effect of the study medication on platelet aggregation was measured twice in each patient during the first 2 months and at each follow-up visit; the dose was individually adjusted. In 76% of the patients receiving aspirin, 50 mg/day gave satisfactory platelet inhibition, 13% needed 60 mg/day, 8% needed 70 mg/day, and 3% needed 100 mg/day. Platelet aggregation was found to be inhibited in only 1.2% of the measurements in the patients receiving placebo. Observation during treatment averaged 21 months; total intention-to-treat follow-up averaged 25 months. For the combined outcome events of transient ischemic attack, stroke, acute myocardial infarction, and vascular death, aspirin reduced risk by 11% (95% confidence limits: -38% to 48%, p greater than 0.1). Thus, there was no significant effect of very-low-dose aspirin in our trial.