Low risk of rebound events after a short course of clopidogrel in acute TIA or minor stroke.

OBJECTIVE: The combination of aspirin and clopidogrel is indicated after acute coronary events and possibly for a short period after TIA or minor ischemic stroke. Early discontinuation of clopidogrel results in a transient rebound increase in risk of recurrence in acute coronary syndromes, but there are no published data on any similar rebound effect in patients with TIA or stroke that might inform the design of clinical trials of aspirin and clopidogrel in the acute phase. METHODS: A 30-day course of aspirin and clopidogrel (both 75 mg daily) was given to high-risk patients with TIA or minor ischemic stroke seen acutely in the EXPRESS study clinic from April 1, 2002, to March 31, 2009. Clopidogrel was stopped after 30 days and aspirin continued. Recurrent events were ascertained at face-to-face follow-up. RESULTS: A total of 320 patients were prescribed a 30-day course of aspirin and clopidogrel acutely after TIA or minor stroke. There were 5 recurrent ischemic strokes and 7 TIAs during the aspirin and clopidogrel treatment period, but no strokes and 4 TIAs during the 30 days after stopping clopidogrel. A similar temporal trend in stroke risk was seen in the 487 patients prescribed aspirin alone in the acute phase, with 12 and 5 strokes in the equivalent time periods. The upper 95% confidence intervals of the observed 0% risk of stroke during the 30 days after stopping clopidogrel was 1.15% overall. CONCLUSION: Although larger studies are required, our findings suggest there is unlikely to be a large rebound effect after discontinuation of a 30-day course of clopidogrel in acute TIA and minor ischemic stroke. However, planned trials of aspirin and clopidogrel in the acute phase after TIA or stroke should still follow-up beyond the cessation of clopidogrel treatment.

Preliminary evidence of a high risk of bleeding on aspirin plus clopidogrel in aspirin-naïve patients in the acute phase after TIA or minor ischaemic stroke.

BACKGROUND: Aspirin plus clopidogrel (A+C) may be more effective than aspirin only (AO) acutely after TIA and minor stroke, but the risk of bleeding in the acute phase is uncertain. We determined this risk, focusing particularly on aspirin-naïve patients. METHODS: We studied consecutive referrals to the EXPRESS study clinic from 1/4/02 to 31/3/08. A 30- to 90-day course of A+C was given to patients presenting acutely. Bleeding events were identified by face-to-face follow-up, diagnostic coding, and blood transfusion data. Unpublished data from the FASTER pilot trial were also studied. RESULTS: Among 633 EXPRESS patients treated with aspirin (+/- clopidogrel), there were 12 spontaneous bleeds (6 minor, 6 major/life-threatening) within 90 days after assessment, with a higher risk for A+C vs. AO (8/247 vs. 4/386, p = 0.047 overall; 5/247 vs. 1/386, p = 0.03 for major/life-threatening bleeds). The excess of major/life-threatening bleeds on A+C vs. AO was seen in aspirin-naïve patients, (4/137 vs. 0/273, p = 0.01), but not in prior-aspirin patients (1/110 vs. 1/113, p = 0.98). All symptomatic bleeds in the FASTER pilot also occurred in aspirin-naïve patients randomized to A+C (6/104 vs. 0/94, p = 0.03). In a pooled analysis, major/life-threatening bleeding on A+C occurred in 9/241 aspirin-naïve patients (90-day risk = 4.8%, 1.6-8.0) versus 1/204 prior-aspirin patients (p = 0.009). CONCLUSION: Although based on relatively few outcomes, the high risk of major bleeding on A+C acutely after TIA or minor stroke in aspirin-naïve patients is a cause for concern. The potential risk to patients is sufficient to mandate detailed monitoring of bleeding risk in ongoing trials and stratify results by whether patients were aspirin-naïve.

Population-based study of risk and predictors of stroke in the first few hours after a TIA.

BACKGROUND: Several recent guidelines recommend assessment of patients with TIA within 24 hours, but it is uncertain how many recurrent strokes occur within 24 hours. It is also unclear whether the ABCD2 risk score reliably identifies recurrences in the first few hours. METHODS: In a prospective, population-based incidence study of TIA and stroke with complete follow-up (Oxford Vascular Study), we determined the 6-, 12-, and 24-hour risks of recurrent stroke, defined as new neurologic symptoms of sudden onset after initial recovery. RESULTS: Of 1,247 first TIA or strokes, 35 had recurrent strokes within 24 hours, all in the same arterial territory. The initial event had recovered prior to the recurrent stroke (i.e., was a TIA) in 25 cases. The 6-, 12-, and 24-hour stroke risks after 488 first TIAs were 1.2% (95% confidence interval [CI]: 0.2-2.2), 2.1% (0.8-3.2), and 5.1% (3.1-7.1), with 42% of all strokes during the 30 days after a first TIA occurring within the first 24 hours. The 12- and 24-hour risks were strongly related to ABCD2 score (p = 0.02 and p = 0.0003). Sixteen (64%) of the 25 cases sought urgent medical attention prior to the recurrent stroke, but none received antiplatelet treatment acutely. CONCLUSION: That about half of all recurrent strokes during the 7 days after a TIA occur in the first 24 hours highlights the need for emergency assessment. That the ABCD2 score is reliable in the hyperacute phase shows that appropriately triaged emergency assessment and treatment are feasible.

Incidence and prognosis of > or = 50% symptomatic vertebral or basilar artery stenosis: prospective population-based study.

The higher risk of early recurrent stroke after posterior circulation transient ischaemic attack or minor stroke versus after carotid territory events could be due to a greater prevalence of large artery stenosis, but there have been few imaging studies, and the prognostic significance of such stenoses is uncertain. Reliable data are necessary to determine the feasibility of trials of angioplasty and stenting and to inform imaging strategies. In the first-ever population-based study, we determined the prevalence of > or = 50% apparently symptomatic vertebral and basilar stenosis using contrast-enhanced MRA in consecutive patients, irrespective of age, presenting with posterior circulation transient ischaemic attack or minor ischaemic stroke in the Oxford Vascular Study and related this to the 90-day risk of recurrent transient ischaemic attack and stroke. For comparison, we also determined the prevalence of > or = 50% apparently symptomatic carotid stenosis on ultrasound imaging in consecutive patients with carotid territory events. Of 538 consecutive patients, 141/151 (93%) had posterior circulation events and had vertebral and basilar imaging, of whom 37 (26.2%) had > or = 50% vertebral and basilar stenosis, compared with 41 (11.5%) patients with > or = 50% ipsilateral carotid stenosis in 357/387 (92%) patients with carotid events who had carotid imaging (OR = 2.74; 95% CI = 1.67-4.51; P = 0.002). Presence of > or = 50% vertebral and basilar stenosis was unrelated to age, sex or vascular risk factors and, in contrast to > or = 50% carotid stenosis was not associated with evidence of coronary/peripheral atherosclerosis. In patients with posterior circulation events, > or = 50% vertebral and basilar stenosis was associated multiple transient ischaemic attacks at presentation (22% versus 3%; OR = 9.29; 95% CI = 2.31-37.27; P < 0.001) and with a significantly higher 90-day risk of recurrent events (OR = 3.2; 95% CI = 1.4-7.0; P = 0.006), reaching 22% for stroke and 46% for transient ischaemic attack and stroke. The prevalence of > or = 50% vertebral and basilar stenosis in posterior circulation transient ischaemic attack or minor stroke is greater than the prevalence of > or = 50% carotid stenosis in carotid territory events, and is associated with multiple transient ischaemic attacks at presentation and a high early risk of recurrent stroke. Trials of interventional treatment are therefore likely to be feasible, but more data are required on the long-term risk of stroke on best medical treatment.