Aspirin May Decrease Intracranial Aneurysm Growth

Batya Swift Yasgur, MA, LSW

October 31, 2019

Aspirin treatment may decrease the rate of growth of intracranial aneurysms (IAs), a new retrospective review suggests.

Investigators used a large database to identify almost 150 patients who had multiple small IAs and found that aspirin treatment was associated with an 80% lower risk for aneurysm growth, compared to a treatment approach that did not include aspirin.

"The major finding is that in this cohort of patients, who have multiple aneurysms, aspirin decreased the risk of aneurysm growth," senior author David Hasan, MD, a professor in the Department of Neurosurgery and Otolaryngology, University of Iowa Carver College of Medicine, Iowa City, told Medscape Medical News.

"We want to see larger trials, because if our findings are validated, aspirin could be a miracle drug [for decreasing aneurysm growth], since it is over-the-counter, has minimal side effects, and is inexpensive," he said.

The study was published online October 29 in the Journal of Neurosurgery.

Gaining Traction

Unruptured IAs "pose a therapeutic dilemma in which the risk-benefit analysis of invasive intervention has to be balanced against the natural history of the disease," the authors write.

According to "current dogma," they write, incidental IAs <5–7 mm should not be treated; however, a "significant proportion of ruptured IAs encountered in clinical practice are smaller than 7 mm," the authors continue.

Moreover, at present, there is "no medical treatment to arrest aneurysm growth and subsequent progression to rupture."

Aspirin has recently "gained traction as a potential therapeutic agent" because it exerts an anti-inflammatory effect on the aneurysm wall, they add.

"In previous work, we looked at the effect of aspirin on brain aneurysm, and other research supported our findings that aspirin decreased the risk of rupture," reported Hasan, whose group validated this finding in animal studies.

However, he noted, previous research has not investigated the effect of aspirin on aneurysm growth, which is considered a biomarker for future rupture.

"If aspirin can prevent growth, it might prevent rupture," he said.

To investigate the question, the researchers retrospectively reviewed a database of all patients who had been treated by Hasan between July 2009 and January 2019.

"This is a population of patients that I followed for 10 years, but we selected patients who had completed 5 years of follow-up," Hasan said.

To be eligible for inclusion in the analysis, patients were required to harbor multiple saccular IAs and to have ≥1 designated primary aneurysms treated by surgical/endovascular means.

The remaining aneurysms were required to be ≤5 mm in size and to have been observed for growth, with ≥5 years of follow-up after the initial treatment.

Additional information gathered by the researchers included demographics, present comorbidities, family and individual medical history, aneurysm size and location in the brain, rupture status of designated primary aneurysms, angiographic features of the aneurysm, treatment modalities, and whether the patient used a daily dose of ≥81 mg of aspirin.

The primary clinical outcome consisted of "the interval growth of any remaining aneurysms that later required treatment."

Any aneurysm that grew during the 5 years was scheduled for treatment.

Of the total number of aneurysms during the study period (n = 2067), 146 patients (mean age, 52.5 ± 13.4 years; 63.5% women) with a total of 375 aneurysms were included in the study.

Comorbidities at baseline included hypertension (13.7%), diabetes mellitus (4.8%), hyperlipidemia (8.9%), family history of IAs (10.96%), sympathomimetic drug use (2.7%), and polycystic kidney disease (PCKD, 6.8%).

Too Soon to Recommend

Of the 375 aneurysms, 146 were treated at the initial encounter. The remaining 229 — which ranged from 2 to 5 mm in size — were observed over time.

The mean size of the designated primary aneurysms treated at the initial encounter was 8.24 ± 2.61 mm (range, 4 – 18 mm).

Of the 229 aneurysms that were watched during the 5-year follow-up period, 10.48% (n = 24) grew to the extent that they required additional treatment.

A univariate analysis showed several predictors of aneurysm growth (all 95% confidence intervals):

  • History of ruptured aneurysm (odds ratio [OR], 3.54; 1.41 – 8.95; P = .007)

  • Sympathomimetic drug abuse (OR, 5.46; .73 – 40.80; P = .10)

  • Hypertension (OR, 8.00; 2.84 – 22.59; P < .001)

  • PCKD (OR, 6.16; 1.63 – 23.31; P = .007)

Results of the univariate analysis indicated that both aspirin use and treatment with stent-assisted coiling (SAC) were associated with a lower chance of growth (OR, .31; P = .02; and OR, .37; P = .08, respectively).

By contrast, hyperlipidemia and aneurysm clipping were associated with a higher chance of growth (OR, 2.51; P = .16; and OR, 2.01; P = .14, respectively)

Independent factors associated with aneurysm growth on multivariate analysis included the following (all 95% confidence intervals):

  • History of a ruptured aneurysm (OR, 5.91; 1.83 – 19.09; P = .003)

  • Hypertension (OR, 14.38; 3.83 – 53.94; P < .001)

  • Sympathomimetic drug abuse (OR, 11.26; 1.21 – 104.65; P = .03)

  • PCKD (OR, 9.48, 1.51 – 59.35; P = .02).

Unlike the findings of the univariate analysis, the multivariate analysis indicated that SAC was no longer protective against growth and that hyperlipidemia was no longer associated with lesion rupture.

On the other hand, aspirin continued to be protective, indicating that aspirin use is "independently protective" against aneurysm growth that would require treatment (OR, 0.19; .05 – .63; P = .007).

"Hence, we estimate that patients who received aspirin therapy have an 80% less chance of aneurysm growth and required treatment over time," the authors summarize.

There were no ruptured aneurysms during the follow-up period.

"Our previous research showed that inflammation is a critical part of the growth and rupture of aneurysms, and aspirin inhibits inflammation in the aneurysm wall, thereby stabilizing it and preventing it from growing and rupturing," Hasan explained.

However, he continued, "it is too early to strongly recommend treatment with aspirin based on our study findings, and physicians should take it with caution, since it was a retrospective study performed at a single institution."

The authors conclude that, given the observational design of the current study, further randomized and prospective studies are needed to validate their findings.

"Wonder Drug"

Commenting on the study for Medscape Medical News, Issam Awad, MD, John Harper Seeley Professor of Surgery (Neurosurgery) and professor of neurology, University of Chicago, called aspirin a "long-known wonder drug that prevents heart attacks and strokes and promises to prevent the growth of unruptured cerebral aneurysms preceding catastrophic rupture."

He noted that retrospective studies "cannot control for all potential confounders mostly related to indications for use of aspirin or lack thereof that could explain the differences in outcome."

A prospective, blinded, randomized trial is "the only way to answer the question rigorously and definitely," said Awad, who was not involved with the study.

"It remains to be seen if a momentum can be generated in large clinical centers and the level of funding can be mobilized for such a trial, while more and more patients might choose to take aspirin anyway or have ever-smaller aneurysms treated rather than followed in clinical practice," he stated.

Hasan added that if the study findings can be replicated in larger studies, "it could have a major impact, both nationally and internationally."

No source of funding for the study was listed. The authors and Awad report no relevant financial relationships.

J Neurosurg. Published online October 29, 2019. Full text

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