Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: association with reduced risk of clinical vasospasm and delayed cerebral ischemia

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OBJECTIVE

Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients.

METHODS

Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression.

RESULTS

Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097–0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01–0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9).

CONCLUSIONS

The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

ABBREVIATIONS ACoA = anterior communicating artery; ADP = adenosine diphosphate; aSAH = aneurysmal SAH; ATP = adenosine triphosphate; CTA = CT angiography; DAPT = dual antiplatelet therapy; DCI = delayed cerebral ischemia; EVD = external ventricular drain; ICA = internal carotid artery; ICU = intensive care unit; MAP = mean arterial pressure; mRS = modified Rankin Scale; SAH = subarachnoid hemorrhage; VP = ventriculoperitoneal.

Article Information

Correspondence David Hasan, Department of Neurosurgery, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242. email: david-hasan@uiowa.edu.

INCLUDE WHEN CITING Published online November 3, 2017; DOI: 10.3171/2017.5.JNS17831.

Disclosures Dr. Broderick reports a financial relationship with AstraZeneca in which the Departments of Neurology and Rehabilitation received money for input on the results of the SOCRATES trial.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Abbreviated flowchart for patients included in this study based on the inclusion and exclusion criteria. AVM = arteriovenous malformation.

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    The proportion of patients with clinical vasospasm and DCI in the DAPT and control groups. The rates of clinical vasospasm and DCI were significantly lower in the DAPT group than in the control group. Error bars indicate 95% confidence intervals.

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    The distribution of severity of clinical vasospasm in the DAPT and control groups. The rate of clinical vasospasm remained significantly lower in the patients on DAPT after adjustment for degree of angiographic vasospasm.

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    Clinical outcome as measured by mRS score depending upon use of DAPT. Increased age and clinical vasospasm were significantly associated with poor outcome. The mRS score ranged from 0 (no symptoms) to 6 (death), with higher scores indicated by increasingly dark shades of gray. The percentage values indicate proportions of the DAPT or control group.

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    Dichotomized clinical outcome as measured by mRS score depending upon use of DAPT. The DAPT group showed a trend toward better outcomes when compared with the control group, although the difference was not statistically significant due to the limited sample size of this single-institution study. The data points represent the percentage of patients in each group who had a good outcome (mRS score of 1 or 2) at discharge; the error bars indicate 95% confidence intervals.

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    Schematic of proposed pathophysiological mechanisms that may underlie clinical vasospasm and DCI in aSAH. Platelets are thought to play a critical role in the development of clinical vasospasm and DCI, and DAPT may mitigate the devastating impacts of clinical vasospasm and DCI through its antiplatelet and antiinflammatory actions. ASA = acetylsalicylic acid (aspirin); Plavix = clopidogrel; TXA2 = thromboxane A2; TXB2 = thromboxane B2. Figure is available in color online only.

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