Impact of pre-ictal antiplatelet therapy use in aneurysmal subarachnoid hemorrhage

https://doi.org/10.1016/j.clineuro.2021.107022Get rights and content

Highlights

  • •

    Aspirin had minimal impact on presentation and outcomes in subarachnoid hemorrhage.

  • •

    In a small retrospective cohort aspirin had no perceived effect on worsening subarachnoid hemorrhagic bleeds.

  • •

    In a small retrospective cohort aspirin had no perceived effect on development of delayed cerebral ischemia.

Abstract

Objective

There is limited evidence on the use of antiplatelet therapy (APT) to reduce the risk and morbidity of cerebral aneurysmal rupture. This analysis retrospectively assessed APT use in patients presenting to our institution with aneurysmal subarachnoid hemorrhage (aSAH).

Methods

We evaluated the records of 186 patients over 7 years of retrospective data from our tertiary care center and an existing database of patients with aSAH. A total of 18 cases with patients on APT and 168 patients not on APT (controls) were identified. Primary outcomes measured were clinical grade (Hunt and Hess score), radiographic grade (Fisher score), and presence of delayed cerebral ischemia (DCI). Secondary outcomes were modified Rankin score at discharge and at 3 months. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment or a decrease in at least 2 points on the Glasgow Coma Scale. Logistic regression models were generated.

Results

We found that APT use did not appear to lead to statistically significant differences in initial presentation, including Hunt-Hess score and Fisher grade (2.91 vs 3.06, p = 0.66, and 3.23 vs 3.22, p = 0.96 respectively). In addition, APT use was not associated with increased rates of delayed cerebral ischemia (DCI) (OR 0.27 p = 0.12). Our analysis showed that increased Hunt Hess score and the presence of DCI are both associated with increased mRS at 90 days (OR 2.32 p < 0.001; OR 2.91 p = 0.002).

Conclusion

The patients in this retrospective observational study did not demonstrate worse outcomes from their aSAH despite APT therapy. Larger prospective studies should be performed to see if this relationship holds and if decreased rates of DCI can be observed.

Introduction

Antiplatelet therapy (APT) is the cornerstone of prevention and treatment in patients with cerebrovascular disease, such as ischemic stroke and carotid artery disease [1], [2]. In neuroendovascular surgery, the use of APT as a premedication prior to aneurysmal coiling, in unruptured aneurysms, and after placement of pipeline stents, has been beneficial in reducing risk of thromboembolic events [3], [4]. Aspirin (ASA) use has also been shown to reduce the risk of intracranial aneurysm rupture [5]. However, literature varies on whether APT can improve outcomes in cases of aneurysmal rupture, with concern that if used in the acute setting, ASA can increase the size of aneurysmal bleeds [6].

One mechanism ASA use may benefit patients with a ruptured aneurysm and subarachnoid hemorrhage (SAH) is by reducing the risk of delayed cerebral ischemia (DCI) [7], [8]. Other studies suggest a higher rate of re-bleeding events with aneurysm rupture in patients on ASA, thus the role of these agents is unclear in SAH [6]. Platelet aggregation and the development of microthrombi after aSAH increase the risk of DCI [7]. Theoretically, inhibition of this process with APT could reduce morbidity.

In this retrospective study, we review an institutional cohort of patients with aSAH, comparing outcomes in patients taking antiplatelet agents before rupture to those not taking antiplatelet agents. The goal of the study is to investigate the impact of antiplatelets on the clinical and radiographic grade of aSAH, rate of DCI, and overall functional outcome.

Section snippets

Study design, setting, and participants

An Institutional Review Board approved, retrospective chart review was conducted over a seven-year period, enrolling patients with SAH secondary to intracranial aneurysmal rupture admitted to Westchester Medical Center – a tertiary care center in Valhalla, New York. In this study, patients were stratified based on whether they were taking an antiplatelet agent (ASA and/or clopidogrel) prior to SAH, compared to the control group of patients not taking any antiplatelet agents at the time of SAH.

Results

A total of 188 patients were initially included, but two patients taking anti-coagulation progressed quickly to brain death while in the emergency room and were excluded. Of the remaining 186 patients, 18 were taking APT at the time of subarachnoid hemorrhage, while 168 were not on antiplatelet agents (Table 1). Table 1 further delineates the demographics of the two groups with a mean age of 53.4 years in the control group and 62.1 years in the treatment group, with the majority of patients in

Discussion

The utility of ASA and other antiplatelet agents is well established for the prevention of thromboembolic events in the neuro-interventional setting [3]. Similarly, the anti-inflammatory effects of ASA and other APTs have been previously elucidated [9]. In this study, we assessed whether patients who had been on APT prior to aneurysm rupture had a decreased incidence of DCI. We found that the incidence of DCI was statistically similar between patients on antiplatelet agents prior to SAH

Conclusion

This study demonstrates that the use of ASA does not necessarily result in worse outcomes in patients who have aSAH. Our data also does not show that the use of antiplatelet agents provides protection against DCI or a poor outcome in SAH. However, the use of ASA was not associated with worsened outcomes, as measured by mRS at 90 days. Our trial does not convincingly answer the question as to whether there is a benefit or a risk of these agents in patients with SAH. Further randomized trials

CRediT authorship contribution statement

Fawaz Al-Mufti: Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft, and was involved in the review and editing of subsequent drafts. Jonathan Ogulnick: Formal analysis, as well as the review and editing of manuscript drafts. Eric Feldstein: Formal analysis, Data curation, as well as the review and editing of manuscript drafts. Nitesh Damodara: Conceptualization, Data curation, Formal analysis, Writing – original draft, and was involved in the review and

Declarations of interest

None.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Submission declaration

This manuscript is a unique submission and is not being considered for publication in part or in full, with any other source in any medium.

Inclusive language declaration

This manuscript is free from bias, stereotypes, slang, reference to dominant culture and/or cultural assumptions.

References (19)

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    Aspirin is a noncompetitive inhibitor of cyclooxygenase; thus it effectively decreases formation of TXA2 (part of the coagulation pathway) and prostaglandins (involved in inflammation). In a study of 186 patients, 18 received aspirin, however, no significant differences were found between patients receiving aspirin and those who did not [72]. Similarly, analyzing 305 patient records, 29 of whom took aspirin prior to SAH onset showed no significant improvements in neurological deficits [73].

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