Article Notes
What's the big deal?
Low-dose daily aspirin is one of the most common drugs taken for cardiovascular disease prophylaxis. Although it's role in secondary prevention is well established, until now it's use for primary prevention in the fit and healthy was controversial – even though it was widely taken by patients and their family doctors alike!
What did they do?
The ASPREE trial (Aspirin in Reducing Events in the Elderly) enrolled 19,114 across the U.S. and Australia, randomizing to 100mg daily aspirin or placebo. Participants were 56% women, median age of 74 and had median follow-up for almost 5 years.
What did they find?
Aspirin did NOT improve either disease-free survival OR reduce cardiovascular disease, although it did increase risk of major hemorrhage. Similarly no benefit was seen for all-cause mortality (in fact, a surprising increase crept in...).
The one group that did see a drop in cardiovascular events were diabetics with no previous cardiovascualr history but who suffered a counteracting increase of major hemorrhage.
But... this study specifically targeted the elderly, who suffer higher rates of antiplatelet-related hemorrhage. Modest benefits have previously been reported in a recently updated meta-analysis though again with a simultaneous increase in major and intracranial bleeding.
Final word... daily aspirin likely causes net harm in the healthy elderly.
Daniel Jolley
What's the story here?
Growing evidence points to significant anti-depressant effects of several anesthetic agents, including ketamine, nitrous oxide, propofol and isoflurane. These may provide avenues for use as novel antidepressants or lead to development of new agents, supplanting other therapies such as ECT.
Why is this important?
Major depression and its consequences contributes to significant disease burden worldwide. Depression prevalence is increasing globally, with one third suffering treatment-resistant depression, unresponsive to modern antidepressant drugs.
Ketamine appears to produce both a fast antidepressant and antisuicidal effect, persisting for up to 1 week. The effect appears dose-responsive in the 0.1 to 0.75 mg/kg range.
Isoflurane when administered to achieve burst suppression (1.5-2 MAC) may have antidepressant effects in 75% of those treated, and achieved full remission in 50% in one 2013 study, comparable to ECT but with fewer cognitive side effects.
N2O use in one small pilot study resulted in depression improvement, likely through similar mechanisms as ketamine. Similarly, propofol-induced burst suppression has also shown an antidepressant effect similar in magnitude to isoflurane.
Bottom line: Several anesthetic agents appear to offer significant antidepressant benefits, which may lead to more mainstream use and supplant ECT. Anesthesiologists will be need to be aware of these effects as they become involved in their provision.
Daniel Jolley