Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

Antiplatelet therapy for secondary prevention of lacunar stroke: a systematic review and network meta-analysis.

PURPOSE: To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS). METHODS: The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0. RESULTS: Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study. CONCLUSIONS: This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.

Different Influences of Statin Treatment in Preventing At-Risk Stroke Subtypes: A Post Hoc Analysis of J-STARS.

AIMS: To understand the different influences of statins on the incidence rate of each stroke subtype in association with low-density lipoprotein (LDL) cholesterol levels, we performed a post hoc analysis on the data from the Japan Statin Treatment Against Recurrent Stroke (J-STARS) study. METHODS: Subjects (n=1,578) were divided into three groups according to their mean postrandomized LDL cholesterol level (＜100, 100-120, and ≥ 120 mg/dL) until the last observation before the event or the end of follow-up. A Cox proportional hazard model for time to events was used for calculating adjusted hazard ratios, 95% confidence intervals, and the trend tests. RESULTS: The event rates for atherothrombotic stroke did not decrease in accordance with the postrandomized LDL cholesterol level subgroups of either the control or the pravastatin group (p=0.15 and 0.33 for the trend, respectively). In the control group, however, no atherothrombotic stroke event was observed in the subgroup of the low postrandomized LDL cholesterol level (less than 100 mg/dL). The event rates for atherothrombotic stroke were lower in the middle postrandomized LDL cholesterol level subgroup (100-120 mg/dL) of the pravastatin group than that of the control group. The event rates for lacunar stroke decreased in the lower postrandomized LDL cholesterol level subgroup of the control group but not of the pravastatin group (p=0.004 and 0.06 for the trend, respectively). CONCLUSIONS: Statins showed different influences on the risks of atherothromobotic and lacunar stroke according to postrandomized LDL cholesterol levels.

Self-Reported Physical Activity and Cardiovascular Disease Risk Factors in Patients with Lacunar Stroke.

BACKGROUND: Physical inactivity is a major modifiable risk factor for stroke. The aim was to explore if stroke patients admitted with lacunar stroke adhere to the international recommendations on physical activity prestroke (≥150 minutes of moderate-intensity activity, or ≥75 minutes of vigorous-intensity activity, or an equivalent combination). Further, to assess association between prestroke physical activity and cardiovascular disease (CVD) risk factors. METHODS: A cross-sectional study, including patients with lacunar stroke according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Data collected included prestroke physical activity using the self-reported Physical Activity Scale. Cardiorespiratory fitness was estimated as the power output from the Graded Cycling Test with Talk Test and sociodemographic factors including age, sex, education, and CVD risk factors including pre-existing diabetes, history of hypertension, body mass index, and lipids were assessed. RESULTS: We included 19 women and 52 men (mean age 64 years). Overall, 79% of the recruited patients adhered to the physical activity recommendations prestroke, but only 35% did vigorous-intensity activity. Prestroke physical activity was associated with a history of hypertension. CONCLUSIONS: A high proportion of the lacunar stroke patients reported to adhere to the recommendations on physical activity prestroke; however, only one third engaged in vigorous-intensity activity. Studies are warranted to investigate if vigorous-intensity activity is effective as secondary prevention in patients with a lacunar stroke.

Aspirin reduced recurrent stroke risk in patients with lacunar stroke.

OBJECTIVES: Lacunar stroke had an unfavorable prognosis in the long term with a high risk of recurrent stroke, aspirin has been widely used to prevent ischemic stroke, but data on the effect of antiplatelet therapy on lacunar infarction are limited. We investigated the long-term effect of aspirin treatment on stroke recurrence risk in patients with lacunar stroke in a multicenter prospective cohort. METHODS: Between November 2000 and November 2001, 2000 consecutive stroke patients (age 35-74 years) were recruited from seven clinical centers. For the present study, a total of 544 patients with lacunar infarction were finally included in the analysis. The patients were divided into two groups (aspirin group, n = 342 and non-aspirin group, n = 202).The effect of aspirin on stroke recurrence was evaluated by using Kaplan-Meier analysis and Cox regression models. RESULTS: During a median 4.1-year follow-up for 544 patients with lacunar stroke, 99 recurrent strokes, 125 major vascular events (stroke, myocardial infarction, and vascular death), 31 vascular deaths, and 59 all-cause deaths were identified. Kaplan-Meier analysis showed that aspirin non-users had a higher risk of future recurrent stroke and of vascular events than did aspirin users (log-rank test, P = 0.049, 0.047, respectively). Aspirin significantly reduced the stroke recurrence in patients with lacunar stroke analyzed with multivariate stepwise analysis using model of Cox proportional hazards with backward elimination (HR = 0.67, 95% CI 0.45-0.99). CONCLUSION: We concluded that aspirin significantly reduced stroke recurrence in patients with lacunar stroke.

Cerebral White Matter Hyperintensities, Kidney Function Decline, and Recurrent Stroke After Intensive Blood Pressure Lowering: Results From the Secondary Prevention of Small Subcortical Strokes ( SPS 3) Trial.

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow-up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1-year follow-up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower- BP -target arm and 8.1% in the higher-target arm (odds ratio=1.40; 95% CI=1.07-1.84). Odds ratio for rapid kidney function decline between lower- and higher-target groups ranged from 1.26 in the lowest WMH tertile (95% CI , 0.80-1.98) to 1.71 in the highest tertile (95% CI , 1.05-2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower-target arm and 9.6% in the higher-target arm (hazard ratio=0.80; 95% CI , 0.63-1.03). Hazard ratio for recurrent stroke in the lower-target group was 1.13 (95% CI , 0.73-1.75) within the lowest WMH tertile compared with 0.73 (95% CI , 0.49-1.09) within the highest WMH tertile ( P for interaction=0.04). Conclusions Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00059306.

Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions.

OBJECTIVE: To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment. METHODS: SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection. RESULTS: CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments. INTERPRETATION: Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207.

Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial.

BACKGROUND: The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. METHODS AND RESULTS: Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06). CONCLUSIONS: In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.

Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial.

UNLABELLED: Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

[Tight control of blood pressure after ischemic stroke is associated with nocturnal hypotension episodes]. / El control estricto de la presion arterial tras un ictus isquemico se asocia con la aparicion de episodios de hipotension nocturna.

AIM: To evaluate whether a tighter blood pressure (BP) control in patients with recent ischemic stroke is associated with the presence of nocturnal hypotension (NHP) episodes. PATIENTS AND METHODS: We included one hundred consecutive patients who had been discharged for ischemic stroke in the previous six months. To evaluate adequacy of BP control in these patients office BP and 24-h ambulatory BP monitoring values were used. RESULTS: We studied 63 males and 37 females; mean age was 69 ± 11 years. Sixty-eight lacunar and 32 non-lacunar strokes were included. Episodes of NHP were observed in 59 patients. Clinical hypertension was present in 34 patients. An abnormal pattern of circadian rhythm of BP was present in 72 subjects. Only 18 patients had BP within normal limits. Episodes of NHP were more frequent in subjects with good BP control versus patients with bad BP control: 88.8% and 52.4 % respectively (p = 0.007). The presence of NHP episodes was also inversely related to number of BP parameters altered (p = 0.001). CONCLUSIONS: Tight control of BP after ischemic stroke is associated with a high frequency of NHP episodes. It is likely that aggressively lowering BP levels within the normal range after an ischemic stroke may be not beneficial, particularly in elderly patients.

TITLE: El control estricto de la presion arterial tras un ictus isquemico se asocia con la aparicion de episodios de hipotension nocturna.Objetivo. Evaluar si un control mas estricto de la presion arterial (PA) en pacientes con ictus isquemico reciente se asocia con la presencia de episodios de hipotension nocturna (HPN). Pacientes y metodos. Se incluyeron 100 pacientes consecutivos que habian sido dados de alta por ictus isquemico en los seis meses previos. Para evaluar el buen control de la PA en estos pacientes, se utilizaron valores de la PA en consulta y monitorizacion ambulatoria de la PA de 24 horas. Resultados. Se estudiaron 63 varones y 37 mujeres; la media de edad fue de 69 ± 11 años. Se incluyeron 68 ictus lacunares y 32 no lacunares. Se observaron episodios de HPN en 59 pacientes. La hipertension clinica estuvo presente en 34 pacientes. Un patron anormal del ritmo circadiano de la PA estaba presente en 72 sujetos. Solo 18 pacientes tenian la PA dentro de limites normales. Los episodios de HPN fueron mas frecuentes en los pacientes con buen control de la PA en comparacion con los pacientes con mal control: 88,8% y 52,4%, respectivamente (p = 0,007). La presencia de episodios de HPN tambien estaba inversamente relacionada con el numero de parametros de PA alterados (p = 0,001). Conclusiones. El control estricto de la PA tras un ictus isquemico se asocia con una alta frecuencia de episodios de HPN. Es probable que una reduccion intensiva de los niveles de la PA dentro del rango de la normalidad tras un ictus isquemico pueda no ser beneficiosa, en particular en los pacientes ancianos.

Recurrent vascular events in lacunar stroke patients with metabolic syndrome and/or diabetes.

OBJECTIVES: We used a prospective clinical trial to examine the risks conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent strokes in the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort. METHODS: The SPS3 trial enrolled 3,020 patients with lacunar strokes. Participants were stratified into groups of METS only, DM only, both, or neither using American Heart Association/National Heart, Lung, and Blood Institute and World Health Organization guidelines. Annualized event rates of strokes, myocardial infarction (MI), and all-cause mortality were calculated, and hazard ratios (HRs) referencing the "neither" group were computed, controlling for significantly associated baseline characteristics. RESULTS: Among 2,999 participants, 25% had METS only, 6% had DM only, 32% had both conditions, and 37%had neither. Over a median of 3.8 years of follow-up, there were 274 recurrent strokes (240 ischemic, 34 hemorrhagic) and 74 MIs; among the 240 ischemic strokes, 134 (56%) were lacunar. The rates of any recurrent stroke (HR 1.7, 95% confidence interval [CI] 1.3­2.3) or lacunar stroke (HR 2.4, 95% CI 1.5­3.7) were significantly higher for those with concurrent METS and DM compared with those who had neither. Risk of incident MI was higher in participants with DM (HR 2.8, 95% CI 1.1­7.0) or concurrent DM and METS (HR 2.6, 95% CI 1.4­4.9). CONCLUSION: METS and DM were significant comorbid conditions in lacunar stroke patients and they were associated with stroke recurrence. In patients with lacunar infarcts, a vigilant approach to prevent development of DM in those with METS may be a potential strategy to reduce recurrent strokes.

Cognitive performance following lacunar stroke in Spanish-speaking patients: results from the SPS3 trial.

BACKGROUND: Cognitive impairment is frequent in lacunar stroke patients. The prevalence and pattern among Spanish-speaking patients are unknown and have not been compared across regions or with English-speaking patients. AIMS: The aim of this study was to characterize cognitive impairment in Spanish-speaking patients and compare it with English-speaking patients. METHODS: The baseline neuropsychological test performance and the prevalence of mild cognitive impairment, defined as a z-score ≤ -1.5 on memory and/or non-memory tests, were evaluated in Spanish-speaking patients in the Secondary Prevention of Small Subcortical Strokes trial. RESULTS: Out of 3020 participants, 1177 were Spanish-speaking patients residing in Latin America (n = 693), the United States (n = 121), and Spain (n = 363). Low education (zero- to eight-years) was frequent in Spanish-speaking patients (49-57%). Latin American Spanish-speaking patients had frequent post-stroke upper extremity motor impairment (83%). Compared with English-speaking patients, all Spanish-speaking patient groups had smaller memory deficits and larger non-memory/motor deficits, with Latin American Spanish-speaking patients showing the largest deficits median z-score -1.3 to -0.6 non-memory tests; ≤5.0 for Grooved Pegboard; -0.7 to -0.3 for memory tests). The prevalence of mild cognitive impairment was high and comparable with English-speaking patients in the United States and Latin American Spanish-speaking patients but not the Spanish group: English-speaking patients = 47%, Latin American Spanish-speaking patients = 51%, US Spanish-speaking patients = 40%, Spanish Spanish-speaking patients = 29%, with >50% characterized as non-amnestic in Spanish-speaking patient groups. Older age [odds ratio per 10 years = 1.52, confidence interval = 1.35-1.71), lower education (odds ratio 0-4 years = 1.23, confidence interval = 0.90-1.67), being a Latin American resident (odds ratio = 1.31, confidence interval = 0.87-1.98), and post-stroke disability (odds ratio Barthel Index <95 = 1.89, confidence interval = 1.43-2.50) were independently associated with mild cognitive impairment. CONCLUSIONS: Mild cognitive impairment in Secondary Prevention of Small Subcortical Strokes Spanish-speaking patients with recent lacunar stroke is highly prevalent but has a different pattern to that observed in English-speaking patients. A combination of socio-demographics, stroke biology, and stroke care may account for these differences.

Stroke: more than meets the eye--big consequences of small strokes.

A long-term outcome analysis in patients with lacunar stroke enrolled in the Secondary Prevention of Small Subcortical Strokes trial highlights the relevance of functional disability after small-vessel strokes. These data support the emerging 'burden of disease' concept in individuals with cerebral microangiopathy, and the role of MRI in outcome prediction.

Vertebrobasilar ectasia in patients with lacunar stroke: the secondary prevention of small subcortical strokes trial.

BACKGROUND: The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke. METHODS: Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE. RESULTS: VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7). CONCLUSIONS: In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure.

Long-term disability after lacunar stroke: secondary prevention of small subcortical strokes.

OBJECTIVES: To determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke. METHODS: SPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0-14). Generalized estimating equations modeled the likelihood of disability (IADL <14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile. RESULTS: Among 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85-0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75-2.75). Americans and Latin Americans had >2-fold greater odds of disability per year compared with Spaniards (p < 0.0001). CONCLUSIONS: In lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.

Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials.

BACKGROUND AND PURPOSE: Lacunar stroke accounts for ≈25% of ischemic stroke, but optimal antiplatelet regimen to prevent stroke recurrence remains unclear. We aimed to evaluate the efficacy of antiplatelet agents in secondary stroke prevention after a lacunar stroke. METHODS: We searched MEDLINE, Embase, and the Cochrane library for randomized controlled trials that reported risk of recurrent stroke or death with antiplatelet therapy in patients with lacunar stroke. We used random effects meta-analysis and evaluated heterogeneity with I(2). RESULTS: We included 17 trials with 42,234 participants (mean age 64.4 years, 65% male) and follow up ranging from 4 weeks to 3.5 years. Compared with placebo, any single antiplatelet agent was associated with a significant reduction in recurrence of any stroke (risk ratio [RR] 0.77, 0.62-0.97, 2 studies) and ischemic stroke (RR 0.48, 0.30-0.78, 2 studies), but not for the composite outcome of any stroke, myocardial infarction, or death (RR 0.89, 0.75-1.05, 2 studies). When other antiplatelet agents (ticlodipine, cilostazol, and dipyridamole) were compared with aspirin, there was no consistent reduction in stroke recurrence (RR 0.91, 0.75-1.10, 3 studies). Dual antiplatelet therapy did not confer clear benefit over monotherapy (any stroke RR 0.83, 0.68-1.00, 3 studies; ischemic stroke RR 0.80, 0.62-1.02, 3 studies; composite outcome RR 0.90, 0.80-1.02, 3 studies). CONCLUSIONS: Our results suggest that any of the single antiplatelet agents compared with placebo in the included trials is adequate for secondary stroke prevention after lacunar stroke. Dual antiplatelet therapy should not be used for long-term stroke prevention in this stroke subtype.