June 13, 2007 (Glasgow) — Results of the pilot phase of the Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER) trial suggest that the addition of clopidogrel to aspirin administered within 24 hours of a transient ischemic attack (TIA) or minor stroke is associated with a reduced risk for recurrent stroke. However, immediate statin use following such events has no significant impact on secondary stroke prevention.
Presented recently at the 16th European Stroke Conference, FASTER — the first randomized trial to evaluate the effects of early aggressive intervention with combination antiplatelet therapy and high-dose statin therapy immediately after minor stroke or TIA — showed a 3.7% reduction in recurrent stroke among individuals on active clopidogrel, compared with placebo.
In contrast, study subjects on active simvastatin had a 3.3% increased risk for recurrent stroke, compared with placebo (10.6% vs 7.3%).
Minor Stroke, Major Risk
"These results suggest that the addition of clopidogrel to aspirin is associated with a reduction in stroke following TIA or minor stroke, [but] it appears unlikely that there is a significant effect of stroke prevention with early statin use. However, both of these conclusions need to be compared in a larger study," said the study's principal investigator, James Kennedy, MB, MSc, from the University of Oxford, in the United Kingdom.
Previous research has shown the risk for recurrent stroke following a TIA or minor stroke is high: approximately 8% at 7 days, 12% at 30 days, and up to 20% at 90 days.
Despite the high risk for recurrence, many patients with TIA or minor stroke are not considered appropriate candidates for tissue plasminogen activator because their symptoms are too "mild" to assume the risks associated with aggressive thrombolysis. However, according to Dr. Kennedy, about one third of these patients ultimately end up either dead or dependent.
Encouraged by results of recent trials in patients with unstable angina, which have shown a benefit of early combination therapy (aspirin and clopidogrel and statin therapy), the aim of the FASTER trial was to determine whether this same benefit would occur in patients with acute symptomatic cerebrovascular disease.
Early Closing
The primary end point of the pilot phase of the study was any stroke at 90 days and stroke severity.
A total of 2885 patients were assessed for study inclusion in the multicenter trial, which included 19 centers in Canada and 1 in the United States. Of these subjects, 2489 were excluded; the remaining 396 participated in the study.
According to Dr. Kennedy, the eligibility criteria for the study focused on those individuals considered to be at highest risk for subsequent deterioration, with either weakness or speech disturbance at the time of symptom onset and symptom duration lasting 5 minutes or longer.
Subjects were ineligible if they were currently on statin therapy, antiplatelet therapy (excluding aspirin), or anticoagulation. Subjects were also excluded if they were candidates for thrombolysis or other acute intervention, or if their stroke was suspected to have a cardioembolic source.
The majority of subjects were excluded because they were on clopidogrel, anticoagulation, or statin therapy. In fact, said Dr. Kennedy, the increasing use of statins over the course of the study, which began in May 2003 and ended in December 2006, played a large role in its failure to meet its enrollment target of 500 subjects, which resulted in its early closing.
Hypothesis Generating
All participants were taking aspirin. Those who weren't taking aspirin at trial entry were given a loading dose of 162 mg and subsequently 81 mg per day. Subjects were randomized to receive clopidogrel (300 mg loading dose plus 75 mg/day) or its placebo, or simvastatin (40 mg/day) or simvastatin placebo within 24 hours of TIA or minor stroke onset for 90 days.
A total of 35 recurrent strokes occurred during the 90-day study period, 2 of which occurred within the first 7 days.
In terms of safety, 2 patients on active clopidogrel experienced intracranial hemorrhage and 4 had systemic hemorrhages (1 severe, 2 moderate, and 1 mild); none of the patients taking placebo experienced hemorrhage.
In addition, 61 (30.8%) subjects in the clopidogrel group experienced asymptomatic hemorrhages or bruising, whereas only 27 (13.9%) in the placebo group did.
The increased use of statins, which ultimately hampered study enrollment, means FASTER is not a feasible trial. However, added Dr. Kennedy, the results of the pilot phase are hypothesis-generating and will inform future resear
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