Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). CONCLUSIONS: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Attentional demands for static postural control after stroke.

OBJECTIVE: To assess the attentional demands associated with postural control among people who have had a stroke. DESIGN: Nonrandomized matched case-control study. SETTING: University research laboratory in Canada. PARTICIPANTS: Six individuals who had suffered a left or right cerebral ischemic attack in the past year and a sample of 6 age- and gender-matched controls. Participants in the stroke group had a mean age of 64.17+/-13.14 years; control participants had a mean age of 64.00+/-13.91 years. Mean National Institute of Health Stroke Scale scores for these patients were 7.67+/-4.92 at the time of stroke and 1.66+/-1.36 at the time of testing. None of the patients were taking medications that would alter cognitive status or balance abilities. INTERVENTION: Participants performed a verbal reaction-time test while engaged in 3 postural tasks (sitting, standing, standing with feet together). MAIN OUTCOME MEASURE: Reaction time: latency between visual stimulus and verbal response. RESULTS: Reaction times in the stroke group differed significantly in all conditions from the controls (410+/-72 ms vs 320+/-54 ms, P<.01). A significant interaction was found between group and postural task (P=.05), with reaction-time scores showing a progressive increase in postural task difficulty among participants who had suffered a stroke. Post hoc comparisons revealed that sitting reaction-time scores were significantly slower than reaction-time scores for feet together standing (P=.008) among participants in the stroke group. CONCLUSION: Individuals who have suffered a stroke showed increased attentional demands for tasks of static postural control compared with healthy, age-matched participants.

Central set influences on gait. Age-dependent effects of postural threat.

We tested the hypothesis that anxiety regarding the potential consequences of a possible fall would alter gait patterns differently between younger and older adults. Sixteen younger and fifteen older adults participated in this study. Participants walked at a self-determined velocity along a 7.2-m walkway under 4 different conditions of postural threat; the walking conditions varied depending on the width constraints of the walkway (0.60 m vs 0.15 m) and the height of the walking surface (floor vs elevated: 0 m vs 0.60 m). Results indicated that although both younger and older adults altered their gait patterns under conditions of increased postural threat, the movement adaptations observed among older adults were substantially different to those adopted by younger adults. These age-dependent differences were strongly evidenced in the joint kinematics and the variability of the gait pattern within each condition. Our findings also indicated that when postural threat increased, the level of muscle activation throughout the gait cycle was altered in the distal musculature (gastrocnemius m. and tibialis anterior m.) among older adults only. Based on the age-related differences observed, we believe that the gait pattern alterations observed among younger and older adults reflect central set modifications to postural control that are mediated by a heightened anxiety imposed by the constraints of the testing conditions. Based on the age-dependent differences in the observed gait pattern modifications, it appears that the effects of anxiety on the control of locomotion are more pervasive for older adults than for younger adults.