From Medscape Medical News > Neurology
Aspirin May Protect Against Intracranial Aneurysm Rupture
Megan Brooks
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November 7, 2011 — Regular use of aspirin may reduce the risk for intracranial aneurysm (IA) rupture, new observational results suggest.
In a group of patients with unruptured aneurysms followed-up for 5 years, those using aspirin at least 3 times a week had a lower likelihood of aneurysmal subarachnoid hemorrhage (SAH) relative to those who did not use aspirin.
"Recent studies on IAs have strengthened the concept that chronic inflammation plays a significant role in aneurysm formation and potentially predisposes to IA wall degeneration and rupture," David M. Hasan, MD, from the Department of Neurosurgery, University of Iowa, Iowa City, and colleagues note in an article published online October 6 inStroke.
The current findings, the authors say, provide epidemiological evidence of an association of frequent aspirin use and reduced incidence of aneurysmal SAH and warrant further study.
In a linked commentary, Michael Tymianski, MD, PhD, FRCSC, from the Division of Neurosurgery, Toronto Western Hospital, Ontario, Canada, agrees that further study is needed before any firm conclusions are drawn.
The association of reduced odds of sustaining an aneurysmal SAH with increased aspirin use "should not, at this stage, be interpreted as a suggestion that aspirin use is of overall clinical value in patients with IAs," Dr. Tymianski writes.
"[T]he possibility of a more adverse clinical outcome in the event of a SAH should be weighed against the possibility of a reduced likelihood of a SAH," he notes.
The ISUIA Cohort
Dr. Hasan and colleagues selected 1691 patients from the prospective untreated cohort of the International Study for Unruptured Intracranial Aneurysms (ISUIA).
Of these patients, 58 had a proven aneurysmal SAH during a 5-year follow-up. Each of these case patients was matched by study site and size of aneurysm to 4 control participants (213 control patients).
In the initial bivariable analysis, a trend of a protective effect for risk for UIA rupture was observed, according to frequency of aspirin use.
Table. Risk for Rupture of Unruptured Aneurysms With Aspirin Use vs No Use
Aspirin Use | Odds Ratio for SAH (95% Confidence Interval) |
3 times a week to daily | 0.40 (0.18 - 0.87) |
<1 time a month | 0.80 (0.31 - 2.05) |
From >1 time a month to 2 times a week | 0.87 (0.27 - 2.81) |
In multivariable analysis, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted odds ratio, 0.27; 95% confidence interval, 0.11 - 0.67; P = .03) relative to those who did not use aspirin.
"Intriguing but Unproven"
In their report, Dr. Hasan and colleagues note that aspirin has inhibitory effects at "several steps in the inflammatory cascade implicated in cerebral aneurysm pathophysiology." Thus, it does have "potential as a therapeutic agent to prevent cerebral aneurysm growth and rupture."
In his commentary, Dr. Tymianski says the possibility that reducing inflammation may reduce hemorrhage risk is "intriguing but unproven," and that the data in this study are "at best an indirect indication in support of this hypothesis."
He says it is unclear from the data whether regular use of aspirin actually affected inflammation, or whether other actions of aspirin such as a reduction in platelet aggregation may have played a role in affecting hemorrhage risk.
The data also cannot rule out a healthy user bias: Regular aspirin users may be more attentive to their health and perhaps have better blood pressure control, for example, Dr. Tymianski says.
Although the authors did use multivariable regression approaches to examine these issues, in this "underpowered data set, these analyses do not exclude these alternative explanations," he writes. Nonetheless, the findings remain "most intriguing," Dr. Tymianski says, and should be explored further.
Dr. Hasan and colleagues suggest studies in animal models of cerebral aneurysms to study the mechanism of the effect of aspirin on the inflammatory process implicated in aneurysm formation and rupture, further observational data from other cohorts or aspirin clinical trials for other end points, and a clinical trial exploring the effect of aspirin on cerebral aneurysms that are chosen to be followed without interventional treatment.
The ISUIA was supported by the National Institute of Neurological Disorders and Stroke. Dr. Hasan and colleagues have disclosed no relevant financial relationships. Dr. Tymianski is president and chief executive officer of NoNO Inc, a company dedicated to the development of neuroprotectants discovered in his academic laboratory.
Medscape Medical News © 2011 WebMD, LLC
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