[show abstract][hide abstract] ABSTRACT: BACKGROUND: Short course of dual antiplatelet therapy for early secondary prevention is a promising treatment for patients with minor stroke or transient ischemic attack at high risk of recurrence. METHODS: We examined the efficacy and safety of dual antiplatelets in patients with transient ischemic attack or minor stroke, defined as National Institute of Health Stroke Scale scores 0-3, in a subgroup analysis of Clopidogrel plus aspirin versus Aspirin alone for Reducing embolization in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR) study. Microembolic signals on transcranial Doppler monitoring was used as surrogate marker for recurrent stroke risk. Patients with ≥1 microembolic signals at baseline were randomized to receive dual therapy (aspirin 75-160 mg daily and clopidogrel 300 mg day 1 then 75 mg daily) or monotherapy (aspirin 75-160 mg daily) for seven-days. RESULTS: Sixty-five of 100 patients recruited had transient ischemic attack or minor stroke: 30 received dual therapy and 35 received monotherapy. Mean onset-to-randomization was 2·3 days in dual therapy group and 3·2 days in monotherapy group (P = 0·03). At day 7, the proportion of patients with ≥1 microembolic signals was 9 of 29 patients in dual therapy group and 18 of 34 patients in monotherapy group (adjusted relative risk reduction 41·4%, 95% CI 29·8-51·1, P < 0·001). The median number of microembolic signals on day 7 was 0 in dual therapy group and 1·0 in monotherapy group (P = 0·046). No patients had intracranial or severe systemic hemorrhage. CONCLUSIONS: Early dual therapy with clopidogrel and aspirin reduces microembolic signals in patients with minor ischemic stroke or transient ischemic attack, without causing significant bleeding complications.
International Journal of Stroke 03/2013; · 2.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Few randomised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis. Microembolic signals, detected by transcranial doppler, are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis. We aimed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke.
The clopidogrel plus aspirin for infarction reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals (CLAIR) trial was a randomised, open-label, blinded-endpoint trial. Between Oct 28, 2003, and Nov 19, 2008, patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were randomly assigned within 7 days of symptom onset to receive clopidogrel (300 mg for the first day, then 75 mg daily) plus aspirin (75-160 mg daily) or aspirin alone (75-160 mg daily) for 7 days. Patients were randomly assigned in blocks of four or six by use of a randomisation website. Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7. The primary endpoint was the proportion of patients who had microembolic signals on day 2. Analysis was by modified intention to treat. All analyses were done by an investigator masked to both patient identity and the day the recording was taken. This trial is registered with the Centre for Clinical Trials, Chinese University of Hong Kong, number CUHK_CCT00164.
100 patients were randomly assigned to clopidogrel plus aspirin (n=47) or aspirin monotherapy (n=53). 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery: 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group. At day 2, 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler (relative risk reduction 42.4%, 95% CI 4.6-65.2; p=0.025). Adverse events were similar in the two groups. No patients had intracranial or severe systemic haemorrhage, but two patients in the dual therapy group had minor haemorrhages.
Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis. Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence.
The Lancet Neurology 03/2010; 9(5):489-97. · 23.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous clinical trials have shown that Neuroaid (MLC601), a traditional Chinese medicine, shows good tolerability and superiority over another traditional Chinese medicine in terms of neurological disability and functional outcome and thus may be beneficial as part of a poststroke rehabilitation program. The safety of MLC601 on hemostasis, hematology and biochemistry has been established in normal subjects and patients with nonacute stroke over a short treatment period. We assessed the safety of Neuroaid in patients with acute stroke treated for 3 months in a substudy of an ongoing randomized placebo-controlled trial.
Laboratory tests (biochemical, hematological and electrocardiogram) were conducted at the month 3 follow-up, in addition to baseline tests. A total of 114 patients were recruited. As there were 13 dropouts, a total of 52 patients on MLC601 and 49 on placebo were available for analysis. Serious adverse events (SAEs) were also analyzed.
There were no statistically or clinically significant differences between treatment groups in biochemical, hematological or electrocardiogram tests at month 3, nor any statistically or clinically significant differences in the absolute and relative changes of the various parameters between baseline and 3 months. SAEs were similar and were those commonly seen in stroke patients.
Longer-term laboratory safety data show no differences between MLC601 and placebo, confirming the safety of MLC601 in acute stroke patients receiving a 3-month treatment.