Diffusion-weighted imaging lesions and risk of recurrent stroke after intracerebral haemorrhage.

OBJECTIVE: To determine whether the presence of diffusion-weighted imaging-positive (DWI+) lesions is associated with recurrent stroke after intracerebral haemorrhage (ICH). METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) assessed the effect of restarting versus avoiding antiplatelet therapy after ICH on major vascular events for up to 5 years. We rated DWI sequences of MRI done before randomisation for DWI+ lesion presence, masked to outcome and antiplatelet use. Cox proportional hazards regression models were used to quantify associations. RESULTS: Of 537 participants in RESTART, 247 (median (IQR) age 75.7 (69.6-81.1) years; 170 men (68.8%); 120 started vs 127 avoided antiplatelet therapy) had DWI sequences on brain MRI at a median of 57 days (IQR 19-103) after ICH, of whom 73 (30%) had one or more DWI+ lesion. During a median follow-up of 2 years (1-3), 18 participants had recurrent ICH and 21 had ischaemic stroke. DWI+ lesion presence was associated with all stroke, (adjusted HR 2.2 (95% CI 1.1 to 4.2)) and recurrent ICH (4.8 (95% CI 1.8 to 13.2)), but not ischaemic stroke (0.9 (95% CI 0.3 to 2.5)). DWI+ lesion presence (0.5 (95% CI 0.2 to 1.3)) vs absence (0.6 (95% CI 0.3 to 1.5), pinteraction=0.66) did not modify the effect of antiplatelet therapy on a composite outcome of recurrent stroke. CONCLUSIONS: DWI+ lesion presence in ICH survivors is associated with recurrent ICH, but not with ischaemic stroke. We found no evidence of modification of effects of antiplatelet therapy on recurrent stroke after ICH by DWI+ lesion presence. These findings provide a new perspective on the significance of DWI+ lesions, which may be markers of microvascular mechanisms associated with recurrent ICH. TRIAL REGISTRATION NUMBER: ISRCTN71907627.

Eligibility for randomized trials of treatments specifically for intracerebral hemorrhage: community-based study.

BACKGROUND AND PURPOSE: Acute treatments specifically for intracerebral hemorrhage (ICH) are being sought in randomized controlled trials. The treatment effect sizes in ongoing and future trials are likely to be small, necessitating large sample sizes. METHODS: We searched online trial registries for randomized controlled trials investigating an acute treatment for ICH. For the trials whose eligibility criteria could be assessed in a prospective, community-based ICH cohort study (2010-2011), we quantified the proportions of patients who were eligible and investigated influences on these proportions. RESULTS: We applied the eligibility criteria of 17 trials to 166 adults with ICH, of whom between 0.6% (95% confidence interval, 0.1-3.3) to 40% (95% confidence interval, 33-48) were eligible for each trial. Fewer patients were eligible for trials restricted to patients randomized within 12 hours of ICH onset (versus trials with a longer time window; P=0.03) and trials restricting eligibility according to premorbid disability (versus trials without this restriction; P=0.046). Each additional eligibility criterion reduced the portion of eligible patients by 1.3% (95% confidence interval, 0.4-2.2; adjusted R(2)=0.47; P=0.004). CONCLUSIONS: Less than half of patients with ICH were eligible for current randomized controlled trials. Future trials could maximize enrollment by minimizing the number of eligibility criteria, maximizing the time window for recruiting patients after ICH onset, permitting premorbid disability, and using a simulator to assess the impact of other eligibility critiera (www.dcn.ed.ac.uk/ICHsimulator/).

Long-term mortality and recurrent vascular events in lacunar versus non-lacunar ischaemic stroke: A cohort study.

Introduction: Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke. Patients and methods: We included first-ever strokes from a hospital-based stroke cohort study recruited in 2002-2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors. Results: We included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1-11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61-1.15) or MI (HR 0.83, 95% CI 0.52-1.34). Conclusion: Long-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.

Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy?

BACKGROUND AND PURPOSE: Differences in risk factor profiles between lacunar and other ischemic stroke subtypes may provide evidence for a distinct lacunar arteriopathy, but existing studies have limitations. We overcame these by pooling individual data on 2875 patients with first-ever ischemic stroke from 5 collaborating prospective stroke registers that used similar, unbiased methods to define risk factors and classify stroke subtypes. METHODS: We compared risk factors between lacunar and nonlacunar ischemic strokes, altering the comparison groups in sensitivity analyses, and incorporated these data into a meta-analysis of published studies. RESULTS: Unadjusted and adjusted analyses gave similar results. We found a lower prevalence of cardioembolic source (adjusted odds ratio, 0.33; 95% CI, 0.24 to 0.46), ipsilateral carotid stenosis (odds ratio, 0.21; 95% CI, 0.14 to 0.30), and ischemic heart disease (odds ratio, 0.75; 95% CI, 0.58 to 0.97) in lacunar compared with nonlacunar patients but no difference for hypertension, diabetes, or any other risk factor studied. Results were robust to sensitivity analyses and largely confirmed in our meta-analysis. CONCLUSIONS: Hypertension and diabetes appear equally common in lacunar and nonlacunar ischemic stroke, but lacunar stroke is less likely to be caused by embolism from the heart or proximal arteries, and the lower prevalence of ischemic heart disease in lacunar stroke provides additional support for a nonatherosclerotic arteriopathy causing many lacunar ischemic strokes. Our findings have implications for how clinicians classify ischemic stroke subtypes and highlight the need for additional research into the specific causes of and treatments for lacunar stroke.

Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.

OBJECTIVE: In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes. METHODS: In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type. RESULTS: Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise. CONCLUSIONS: Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.

Differences between ischemic stroke subtypes in vascular outcomes support a distinct lacunar ischemic stroke arteriopathy: a prospective, hospital-based study.

BACKGROUND AND PURPOSE: Whether and how the arterial pathology underlying lacunar ischemic stroke differs from the atherothrombotic processes causing most other ischemic strokes is still debated. Different risks of recurrent stroke and MI after lacunar versus nonlacunar ischemic stroke may support a distinct lacunar arteriopathy. METHODS: We prospectively followed a hospital-based cohort of 809 first-ever ischemic stroke patients for 1 to 4 years. We compared risks of death, recurrent stroke, and MI in patients with lacunar versus nonlacunar stroke, and performed an updated meta-analysis of recurrent stroke subtype patterns. RESULTS: During 1725 person-years of follow-up, 109 patients had a recurrent stroke and 31 had MI. All patients at baseline, and 93% with recurrent stroke, had brain imaging and more than half with recurrent stroke had diffusion-weighted MRI. Overall, there was no difference in recurrence risk after lacunar vs nonlacunar stroke, although there was a trend toward a lower recurrence risk in the early weeks after lacunar stroke. Lacunar recurrence was more likely after lacunar than nonlacunar stroke (OR, 6.5; 95% CI, 2.4-17.5; updated meta-analysis OR, 6.8; 95% CI, 4.2-11.2). MI risk was nonsignificantly lower after lacunar than nonlacunar stroke (rate ratio, 0.5; 95% CI, 0.2-1.1; rate ratio after excluding patients with previous ischemic heart disease: 0.3; 95% CI, 0.1-0.9). CONCLUSIONS: Our finding of a trend toward a lower MI risk after lacunar vs nonlacunar stroke and confirmation of both a lower early recurrence risk after lacunar stroke and a tendency of recurrent stroke subtypes to "breed true" support the notion of a distinct nonatherothrombotic lacunar arteriopathy.

Clinical diagnosis of TIA or minor stroke and prognosis in patients with neurological symptoms: A rapid access clinic cohort.

BACKGROUND: The long-term risk of stroke or myocardial infarction (MI) in patients with minor neurological symptoms who are not clinically diagnosed with transient ischaemic attack (TIA) or minor stroke is uncertain. METHODS: We used data from a rapid access clinic for patients with suspected TIA or minor stroke and follow-up from four overlapping data sources for a diagnosis of ischaemic or haemorrhagic stroke, MI, major haemorrhage and death. We identified patients with and without a clinical diagnosis of TIA or minor stroke. We estimated hazard ratios of stroke, MI, major haemorrhage and death in early and late time periods. RESULTS: 5,997 patients were seen from 2005-2013, who were diagnosed with TIA or minor stroke (n = 3604, 60%) or with other diagnoses (n = 2392, 40%). By 5 years the proportion of patients who had a subsequent ischaemic stroke or MI, in patients with a clinical diagnosis of minor stroke or TIA was 19% [95% confidence interval (CI): 17-20%], and in patients with other diagnoses was 10% (95%CI: 8-15%). Patients with clinical diagnosis of TIA or minor stroke had three times the hazard of stroke or MI compared to patients with other diagnoses [hazard ratio (HR)2.83 95%CI:2.13-3.76, adjusted age and sex] by 90 days post-event; however from 90 days to end of follow up, this difference was attenuated (HR 1.52, 95%CI:1.25-1.86). Older patients and those who had a history of vascular disease had a high risk of stroke or MI, whether or not they were diagnosed with minor stroke or TIA. CONCLUSIONS: Careful attention to vascular risk factors in patients presenting with transient or minor neurological symptoms not thought to be due to stroke or TIA is justified, particularly those who are older or have a history of vascular disease.