Lesly A Pearce

McMaster University, Hamilton, Ontario, Canada

Are you Lesly A Pearce?

Claim your profile

Publications (67)505.19 Total impact

  • Majid F Bakheet, Lesly A Pearce, Robert G Hart
    [Show abstract] [Hide abstract]
    ABSTRACT: Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2·1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2·0, 95% CI 1·0, 3·8; P = 0·04; fixed effects model; I(2) for heterogeneity of 0%, P = 0·51). The average absolute incidence of subdural hematoma averaged 1·1 (95%CI 0·7,1·6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1·1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone. © 2014 World Stroke Organization.
    International Journal of Stroke 12/2014; DOI:10.1111/ijs.12419 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The primary outcome results for the SPS3 trial suggested that a lower systolic target blood pressure (<130 mm Hg) might be beneficial for reducing the risk of recurrent stroke compared with a higher target (130-149 mm Hg), but that the addition of clopidogrel to aspirin was not beneficial compared with aspirin plus placebo. In this prespecified secondary outcome analysis of the SPS3 trial, we aimed to assess whether blood pressure reduction and dual antiplatelet treatment affect changes in cognitive function over time in patients with cerebral small vessel disease. In the SPS3 trial, patients with recent (within 6 months) symptomatic lacunar infarcts from 81 centres in North America, Latin America, and Spain were randomly assigned, in a two-by-two factorial design, to target levels of systolic blood pressure (1:1; 130-149 mm Hg vs <130 mm Hg; open-label) and to a once-daily antiplatelet treatment (1:1; aspirin 325 mg plus clopidogrel 75 mg vs aspirin 325 mg plus placebo; double-blind). For this analysis, the main cognitive outcome was change in Cognitive Abilities Screening Instrument (CASI) during follow-up. Patients were tested annually for up to 5 years, during which time the mean difference in systolic blood pressure was 11 mm Hg (SD 16) between the two targets (138 mm Hg vs 127 mm Hg at 1 year). We used linear mixed models to compare changes in CASI Z scores over time. The SPS3 trial is registered with ClinicalTrials.gov, number NCT00059306. The study took place between March 23, 2003, and April 30, 2012. 2916 of 3020 SPS3 participants (mean age 63 years [SD 11]) with CASI scores at study entry were included in the analysis, with a median follow-up of 3·0 years (IQR 1·0-4·9). Mean changes in CASI Z scores from study entry to assessment at years 1 (n=2472), 2 (n=1968), 3 (n=1521), 4 (n=1135), and 5 (n=803) were 0·12 (SD 0·83), 0·15 (0·84), 0·16 (0·95), 0·19 (0·99), and 0·14 (1·09), respectively. Changes in CASI Z scores over time did not differ between assigned antiplatelet groups (p=0·858) or between assigned blood pressure target groups (p=0·520). There was no interaction between assigned antiplatelet groups and assigned blood pressure target groups and change over time (p=0·196). Cognitive function is not affected by short-term dual antiplatelet treatment or blood pressure reduction in fairly young patients with recent lacunar stroke. Future studies of cognitive function after stroke should be of longer duration or focus on patients with higher rates of cognitive decline. US National Institute of Neurological Disorders and Stroke. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 12/2014; 13(12):1177-85. DOI:10.1016/S1474-4422(14)70224-8 · 21.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Purpose-Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes. Methods-We studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on diffusion-weighted imaging. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3-dimensional reconstruction of axial MRI slices. Results-Infarct shape was ovoid/spheroid in 63%, slab in 12%, stick in 7%, and multicomponent in 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 mL, respectively (P<0.001). Distributions of vascular risk factors were similar across the 4 groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multicomponent had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (P=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred during an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume. Conclusions-In patients with recent lacunar stroke, vascular risk factor profile was similar among the different infarct shapes and sizes. Infarct size correlated with worse short-term functional outcome. Neither shape nor volume was predictive of stroke recurrence.
    Stroke 09/2014; 45(10). DOI:10.1161/STROKEAHA.114.005211 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Purpose-The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. Methods-We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. Results-During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin <13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m(2) decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). Conclusions-Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain.
    Stroke 08/2014; 45(10). DOI:10.1161/STROKEAHA.114.005789 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Neuroimaging manifestations of small vessel disease are heterogeneous, and correlation with patient features has not been adequately characterized.AimOur goal was to correlate magnetic resonance imaging findings with clinical features in a large multiethnic cohort with recent lacunar stroke.Methods Patient characteristics were correlated with neuroimaging results in the Secondary Prevention of Small Subcortical Stroke study participants.ResultsAmong 3005 patients, mean age was 63 years; 62% were men; and 51%, 30%, and 16% were non-Hispanic White, Hispanic, and Black, respectively. Recent lacunar infarcts were distributed between the subcortical hemisphere (31%), thalamus (26%), brainstem/cerebellum (26%), and basal ganglia/internal capsule (16%). Multiple lacunar infarcts (i.e., acute and remote) were present in 40% and associated with increased age (OR 1·3 per 20 years, 95% CI 1·1, 1·5), male gender (OR 1·5, CI 1·3, 1·7), hypertension (OR 1·5, CI 1·2, 1·8), increased systolic blood pressure (OR 1·2 per 20 mmHg, CI 1·1, 1·3), and prior stroke (OR 3·8, CI 2·9, 5·0). Moderate-severe white matter hyperintensities were present in 50% and associated with increased age (OR 4·3 per 20 years, CI 3·4, 5·4), hypertension (OR 1·8, CI 1·4, 2·3), increased systolic blood pressure (OR 1·3 per 20 mmHg, CI 1·1, 1·5), increased diastolic blood pressure (OR 1·2 per 10 mm, CI 1·0, 1·3), and prior stroke (OR 3·3, CI 2·3, 4·5). Infarct location varied significantly by race-ethnicity (P < 0·001), with Blacks and Hispanics having more infarcts in the brainstem/cerebellum than non-Hispanic Whites, and by gender with women more often having thalamic lacunes than men (P ≤ 0·001).Conclusions In patients with recent lacunar stroke, infarct location and number have distinctie associations with gender, vascular risk factors, and race-ethnicity, demonstrating the complex pathogenesis of lacunar stroke and cerebral small artery disease.
    International Journal of Stroke 06/2014; 9(8). DOI:10.1111/ijs.12282 · 4.03 Impact Factor
  • Ben J Connolly, Lesly A Pearce, Robert G Hart
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Purpose-Subdural hematomas are an important bleeding complication of anticoagulation. We quantify the risk of subdural hematoma associated with anticoagulation with vitamin K antagonists (VKAs) compared with other oral antithrombotic therapies. Methods-Randomized trials were identified from the Cochrane Central Register of Controlled Trials and were included if published since 1980 and compared oral VKAs with antiplatelet therapy or with direct-acting oral anticoagulants. Two reviewers independently extracted data with differences resolved by joint review. Results-Nineteen randomized trials were included that involved 92 156 patients and 275 subdural hematomas. By meta-analysis, VKAs were associated with a significantly increased risk of subdural hematoma (odds ratios, 3.0; 95% confidence interval, 1.5-6.1) compared with antiplatelet therapy (9 trials, 11 603 participants). The risk of subdural hematoma was also significantly higher with VKAs versus factor Xa inhibitors (meta-analysis odds ratios, 2.9; 95% confidence interval, 2.1-4.1; 5 trials, 49 687 patients) and direct thrombin inhibitors (meta-analysis odds ratios, 1.8; 95% confidence interval, 1.2-2.7; 5 trials, 30 866 patients) versus VKAs. The absolute rate of subdural hematoma among 24 485 patients with atrial fibrillation treated with VKAs pooled from 6 trials testing direct-acting oral anticoagulants was 2.9 (95% confidence interval, 2.5-3.5) per 1000 patient-years. Conclusions-VKA use significantly increases the risk of subdural hematoma by approximate to 3-fold relative to antiplatelet therapy. Direct-acting oral anticoagulants are associated with a significantly reduced risk of subdural hematomas versus VKAs. Based on indirect comparisons to VKAs, the risks of subdural hematoma are similar with antiplatelet monotherapies and factor Xa inhibitors.
    Stroke 06/2014; 45(6):1672-8. DOI:10.1161/STROKEAHA.114.005430 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background While living with others has been associated with improved functional outcome after acute stroke, it is unclear if this affects adherence to stroke prevention measures.AimsWe examined the relationship between living arrangements and adherence to antiplatelet therapy assignment and participation status in an international randomized trial for secondary stroke prevention.Method Antiplatelet therapy adherence, trial retention outcomes, and baseline characteristics for participants enrolled in the Secondary Prevention of Small Subcortical Strokes study were compared between those who lived alone vs. with others (n = 2374). Participant status at end-of-trial was categorized into (1) on assigned antiplatelet, (2) off assigned antiplatelet by participant request, or (3) participant withdrew consent/lost to follow-up. Multivariable multivariate logistic regression was used to identify patient features at entry predictive of participant status at trial end.ResultsLiving arrangement, alone vs. with other(s), was not significantly associated with participant status. Participants enrolled in the United States/Canada (odds ratio 3·1, confidence intervals 2·0–5·0, vs. Latin America), taking more (7+) prescription medications (odds ratio 1·7, confidence intervals 1·1–2·7, vs. 0–2 medications), and scoring lower on the Stroke Specific Quality of Life scale (odds ratio 1·3, confidence intervals 1·1–1·5, per 10 points) were more likely to withdraw or become lost to follow-up in the study vs. completing the study on assigned antiplatelet therapy. Participants enrolled in the United States/Canada (odds ratio 5·0, confidence intervals 2·4–10·0, vs. Latin America) and taking fewer (0–2) medications (odds ratio 1·9, confidence intervals 1·2–3·1 vs. 3–6 medications) were more likely to request discontinuation of assigned antiplatelet medication vs. completing the study.Conclusion Living with others was not independently predictive of protocol adherence in this cohort. Number of medications and Stroke Specific Quality of Life scale score may be more indicative of likelihood of trial participation and acceptance of long-term antiplatelet regimen.
    International Journal of Stroke 04/2014; 9(4). DOI:10.1111/ijs.12267 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 06/2013; 23(4). DOI:10.1016/j.jstrokecerebrovasdis.2013.05.021 · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: It remains controversial whether dual antiplatelet therapy reduces stroke more than aspirin alone. AIM: We aimed to assess the effects of adding clopidogrel to aspirin on the occurrence of stroke and major haemorrhage in patients with vascular disease. METHODS: Meta-analysis of published randomized trials comparing the combination of clopidogrel and aspirin vs. aspirin alone that reported stroke and major bleeding. RESULTS: Thirteen randomized trials were included with a total of 90 433 participants (mean age 63 years; 63% male) with a mean follow-up of 1·0 years and 2011 strokes. Stroke was reduced 19% by dual antiplatelet therapy (odds ratio = 0·81, 95% confidence interval 0·74-0·89) with no evidence of heterogeneity of effect across different trial populations (I(2) index = 5%, P = 0·4 for heterogeneity). Dual antiplatelet therapy reduced ischemic stroke by 23% (odds ratio = 0·77; 95% confidence interval 0·70-0·85); there was a nonsignificant 12% increase in intracerebral haemorrhage (odds ratio = 1·12, 95% confidence interval 0·86-1·46). Among 1930 participants with recent (<30 days) brain ischemia from four trials, stroke was reduced by 33% (odds ratio = 0·67, 95% confidence interval 0·46-0·97) by dual antiplatelet therapy vs. aspirin alone. The risk of major bleeding was increased by 40% (odds ratio = 1·40, 95% confidence interval 1·26-1·55) by dual antiplatelet therapy. CONCLUSIONS: This meta-analysis demonstrates a substantial relative risk reduction in stroke by clopidogrel plus aspirin vs. aspirin alone that is consistent across different trial cohorts. Major haemorrhage is increased by dual antiplatelet therapy.
    International Journal of Stroke 05/2013; DOI:10.1111/ijs.12050 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Subdural hematomas are an important bleeding complication of antithrombotic therapies. We sought to characterize the risk of subdural hematoma associated with antiplatelet therapy. METHODS: Trials were gathered from the Cochrane Central Register of Controlled Trials and from recent meta-analyses of trials regarding antiplatelet therapy for the primary prevention of stroke. Randomized trials published since 1980 comparing antiplatelet therapy with placebo or control and reporting subdural hematoma were included in the analysis. For recent large trials that did not report subdural hematomas, unpublished results were sought. Two reviewers independently extracted data on study design and subdural hematomas, with differences resolved by joint review and consensus. RESULTS: Four published trials were identified that compared aspirin with placebo/control involving 6565 participants (mean age 66 years) with 8 total subdural hematomas. Unpublished data from 5 aspirin trials with 90,689 participants reported 18 total subdural hematomas. The incidence of subdural hematomas varied from 0.02 per 1000 patient-years for primary prevention trials of middle-aged health professionals to 1 to 2 per 1000 patient-years for older patients with atrial fibrillation. Pooled data from all 9 trials revealed an odds ratio of 1.6 (95% confidence interval 0.8-3.5; heterogeneity P = .8; I(2) index 0%) for antiplatelet therapy and risk of subdural hematoma. CONCLUSIONS: Based on the limited available data, it is uncertain whether aspirin therapy increases the risk of subdural hematoma: the observed 1.6-fold increased risk was not statistically significant. The incidence of subdural hematoma during aspirin therapy is low but varies widely depending upon the age of the patient population.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 02/2013; DOI:10.1016/j.jstrokecerebrovasdis.2013.01.007 · 1.99 Impact Factor
  • Robert G. Hart, John W. Eikelboom, Lesly A. Pearce
    JAMA Neurology 12/2012; 69(12):1641. DOI:10.1001/archneurol.2012.2691 · 7.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lacunar strokes are a leading cause of cognitive impairment and vascular dementia. However, adequate characterization of cognitive impairment is lacking. The aim of this study was to estimate the prevalence and characterize the neuropsychological impairment in lacunar stroke patients. All English-speaking participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (National Clinical Trial 00059306) underwent neuropsychological testing at baseline. Raw scores were converted to z scores using published norms. Those with impairment (z ≤ -1.5) in memory and/or nonmemory domains were classified as having mild cognitive impairment (MCI). Among the 1,636 participants, average z scores on all tests were <0, with the largest deficits seen on tests of episodic memory (range of means, -0.65 to -0.92), verbal fluency (mean, -0.89), and motor dexterity (mean, -2.5). Forty-seven percent were classified as having MCI (36% amnestic, 37% amnestic multidomain, 28% nonamnestic). Of those with modified Rankin score 0-1 and Barthel score = 100, 41% had MCI. Younger age (odds ratio [OR] per 10-year increase, 0.87), male sex (OR, 1.3), less education (OR, 0.13-0.66 for higher education levels compared to 0-4 years education), poststroke disability (OR, 1.4), and impaired activities of daily living (OR, 1.8) were independently associated with MCI. In this large, well-characterized cohort of lacunar stroke patients, MCI was present in nearly half, including many with minimal or no physical disabilities. Cognitive dysfunction in lacunar stroke patients may commonly be overlooked in clinical practice but may be as important as motor and sensory sequelae. ANN NEUROL 2012;72:351-362.
    Annals of Neurology 09/2012; 72(3):351-62. DOI:10.1002/ana.23733 · 11.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.).
    New England Journal of Medicine 08/2012; 367(9):817-25. DOI:10.1056/NEJMoa1204133 · 54.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≥14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. Twelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95% CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74-0.91). The addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.
    Stroke 08/2012; 43(8):2157-62. DOI:10.1161/STROKEAHA.112.656173 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study examined the baseline characteristics, racial/ethnic differences, and geographic differences among participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) study. The SPS3 trial enrolled patients who experienced a symptomatic small subcortical stroke (lacunar stroke) within the previous 6 months and an eligible lesion on detected on magnetic resonance imaging. The patients were randomized, in a factorial design, to antiplatelet therapy (aspirin 325 mg daily plus clopidogrel 75 mg daily vs aspirin 325 mg daily plus placebo) and to one of two levels of systolic blood pressure targets ("intensive" [<130 mmHg] or "usual" [130-149 mmHg]). A total of 3020 participants were recruited from 81 clinical sites in 8 countries. In this cohort, the mean age was 63 years, 63% were men, 75% had a history of hypertension, and 37% had diabetes. The racial distribution was 51% white, 30% Hispanic, and 16% black. Compared with white subjects, black subjects were younger (mean age, 58 years vs 64 years; P <.001) and had a higher prevalence of hypertension (87% vs 70%; P <.001). The prevalence of diabetes was higher in the Hispanic and black subjects compared with the white subjects (42% and 40% vs 32%; both P <.001). Tobacco smoking at the time of qualifying stroke was much more frequent in the Spanish participants than in subjects from North America and from Latin America (32%, 22%, and 9%, respectively; P <.001). Mean systolic blood pressure at study entry was 4 mmHg lower in the Spanish subjects compared with the North American subjects (P <.01). The SPS3 cohort is the largest magnetic resonance imaging-defined series of patients with S3. Among the racially/ethnically diverse SPS3 participants, important differences in patient features and vascular risk factors could influence prognosis for recurrent stroke and response to interventions.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 04/2012; DOI:10.1016/j.jstrokecerebrovasdis.2012.03.002 · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown. Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%). Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively). Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.
    Clinical Journal of the American Society of Nephrology 09/2011; 6(11):2599-604. DOI:10.2215/CJN.02400311 · 5.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obstructive sleep apnea (OSA) is associated with hypertension (HTN) and cardiovascular disease. Transient episodes of hypoxia, hypercapnia, and blood pressure elevation during OSA may lead to neural damage and subsequently white matter disease (WMD). As WMD is usually the result of chronic small vessel ischemia, a relationship between OSA and cerebrovascular disease may exist. This case series aimed to establish a relationship between OSA and WMD. Sixty-two patients without cerebrovascular disease who had both a polysomnogram and brain magnetic resonance imaging were identified. All patients carried the diagnosis of HTN. WMD was evaluated using the age-related white matter changes scale. Although half of the study population had WMD on magnetic resonance imaging, no association was found between WMD with severity of OSA (P=0.9). Our results are limited by the small sample size and by coexistent HTN in all patients. Further studies are needed to elucidate the relationship between OSA and WMD, especially among nonhypertensive patients. Future research should also address if OSA treatment has any effect on WMD.
    The Neurologist 09/2011; 17(5):289-91. DOI:10.1097/NRL.0b013e31821a25d6 · 1.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events. Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n = 3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy--325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind--and to one of two levels of systolic blood pressure targets--'intensive' (<130 mmHg) vs. 'usual' (130-149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment. Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.
    International Journal of Stroke 04/2011; 6(2):164-75. DOI:10.1111/j.1747-4949.2010.00573.x · 4.03 Impact Factor
  • Robert G Hart, Lesly A Pearce
    Stroke 06/2009; 40(7):2607-10. DOI:10.1161/STROKEAHA.109.549428 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Treatments to slow the progression are a major unmet need in Parkinson's disease. Detailed assessment of randomized trials testing putative neuroprotective drugs was undertaken to inform the design, reporting, and interpretation of future studies. This study is a systematic review of trials testing neuroprotective drugs. Data were extracted independently by two coauthors. Fifteen completed, published trials involving 4,087 participants tested 13 different drugs in 18 double-blind comparisons with placebo. Seven comparisons involving 2,000 subjects assessed MAO-B inhibitors. The primary outcome was change in the Unified Parkinson's Disease Rating Scale score in eight trials and time to need for dopaminergic therapy in seven. Mean participant age was 62 years, 35% were women, the interval from diagnosis to entry averaged 11 months, and the number of participants averaged 272 (largest = 806). Follow-up averaged <16 months in all but two trials. Detailed randomization methods and success of double-blinding were reported in 20% and 13%, respectively. Based on the investigators' conclusions, six trials were interpreted as consistent with a neuroprotective effect, three as negative, and five as either confounded or not meeting criteria for futility. Neuroprotection trials have involved relatively uniform groups of participants early in the clinical disease course, with outcomes weighted heavily toward motor deterioration. Future trials should include participants with wider ranges of disease stages and assess broader neurological outcomes.
    Movement Disorders 04/2009; 24(5):647-54. DOI:10.1002/mds.22432 · 5.63 Impact Factor

Publication Stats

5k Citations
505.19 Total Impact Points


  • 2014
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
  • 1994–2012
    • University of Texas Health Science Center at San Antonio
      • • School of Nursing
      • • Department of Neurology
      • • Division of Hospital Medicine
      San Antonio, TX, United States
  • 1996–2011
    • Mayo Foundation for Medical Education and Research
      • • Department of Neurology
      • • Division of Cardiovascular Diseases
      Scottsdale, AZ, United States
  • 1999–2006
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • The University of Arizona
      • Department of Neurology
      Tucson, AZ, United States
    • Southern Illinois University School of Medicine
      Springfield, Illinois, United States
  • 2005
    • Birmingham City University
      Birmingham, England, United Kingdom
  • 2000
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
    • Mount Sinai Medical Center
      New York City, New York, United States