Association of Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. Design, Setting, and Participants: A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. Exposures: Prestroke treatment with NOACs within 7 days prior to alteplase treatment. Main Outcomes and Measures: The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. Results: Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). Conclusions and Relevance: Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

Effect of a cellulose-containing weight-loss supplement on gastric emptying and sensory functions.

CM3, a highly cross-linked cellulose in capsule form, expands in the stomach to a size several fold of its original volume. It is purported to induce a prolonged feeling of satiation and a delay in gastric emptying, thus promoting weight loss. We examined whether CM3 delays gastric emptying (using the stable isotope (13)C-octanoic breath test) and whether it influences subjective feelings of appetite sensations (using visual analog scales, VASs). We performed a double-blind randomized placebo-controlled crossover trial in 19 moderately obese but otherwise healthy subjects (mean age 55 +/- 9 years, BMI 31.1 +/- 4.6 kg/m(2)). The subjects were treated with six capsules of CM3 or matching placebo 30 min before a standardized solid meal. Breath collection and VASs were performed over 4 h every 15 min and 30 min, respectively. Half-excretion time of (13)CO(2) in breath, indicating gastric emptying half time, was the primary outcome parameter. The study was powered to detect a change in gastric emptying of 20-30 min. Mean (13)CO(2) half-excretion time changed from 2.3 +/- 0.4 to 2.4 +/- 0.33 h (mean difference +6 min, 95% confidence interval (CI) -3 to +15 min; P = 0.17). Appetite sensations (hunger, satiation, fullness, prospective food consumption, desire to eat something sweet, salty, savory, or fatty) changed over time during the course of the postprandial phase but were not influenced by CM3 (repeated measures ANOVA). In obese subjects, acute administration of the weight-loss supplement CM3 does not delay gastric emptying and does not influence subjective appetite sensations.