12 research outputs found
Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease
BACKGROUND
We evaluated whether rivaroxaban alone or in combination with aspirin would be more
effective than aspirin alone for secondary cardiovascular prevention.
METHODS
In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg
once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after
a mean follow-up of 23 months.
RESULTS
The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group
than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard
ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major
bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288
patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05;
P<0.001). There was no significant difference in intracranial or fatal bleeding between
these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group
as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI,
0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome
did not occur in significantly fewer patients in the rivaroxaban-alone group than in the
aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.
CONCLUSIONS
Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more
major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice
daily) alone did not result in better cardiovascular outcomes than aspirin alone and
resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov
number, NCT01776424.
Individual and combined effects of cannabidiol and Δ<sup>9</sup>-tetrahydrocannabinol on striato-cortical connectivity in the human brain
BACKGROUND: Cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) are the two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular, the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. AIMS: To examine effects of THC, CBD, and THC + CBD on functional connectivity of striatal sub-divisions (associative, limbic and sensorimotor). METHOD: Resting-state functional Magnetic Resonance Imaging (fMRI) was used across two within-subjects, placebo-controlled, double-blind studies, with a unified analysis approach. RESULTS: Study 1 (N = 17; inhaled cannabis containing 8 mg THC, 8 mg THC + 10 mg CBD or placebo) showed strong disruptive effects of both THC and THC + CBD on connectivity in the associative and sensorimotor networks, but a specific effect of THC in the limbic striatum network which was not present in the THC + CBD condition. In Study 2 (N = 23, oral 600 mg CBD, placebo), CBD increased connectivity in the associative network, but produced only relatively minor disruptions in the limbic and sensorimotor networks. OUTCOMES: THC strongly disrupts striato-cortical networks, but this effect is mitigated by co-administration of CBD in the limbic striatum network. Oral CBD administered has a more complex effect profile of relative increases and decreases in connectivity. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis-related disorders, and the development of cannabinoid therapeutics