Authors: Oppong MD, Gembruch O, Pierscianek D, et al. Post-treatment antiplatelet therapy reduces risk for delayed cerebral ischemia due to aneurysmal subarachnoid hemorrhage. Neurosurgery 2018; 0: 1-7.
Reviewed by: Kyle Hobbs, MD, Director, Neurocritical Care Fellowship, Assistant Professor of Neurology, Wake Forest School of Medicine
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Delayed cerebral ischemia (DCI) occurs in approximately 30 percent of patients after aneurysmal subarachnoid hemorrhage (SAH). Activation of platelets and thromboxane A2 has been associated with development of DCI, but the benefit of antiplatelet agents after SAH has not been established. This single center retrospective case-control study was based on an observational cohort of all patients admitted with aneurysmal SAH who underwent endovascular aneurysm treatment between 2003 and 2016. Patients were grouped into an “intervention” group or a “control” group based on whether they received antiplatelet therapy after endovascular aneurysm treatment or not. Further subgroup analysis compared intervention group patients with mono- versus dual-antiplatelet therapy. Antiplatelet therapy consisting of aspirin 100 mg for at least three weeks was given in the intervention group based on estimated risk of postprocedural thromboembolism (wide aneurysm base, coil in vessel lumen); if the patient required stent placement, clopidogrel 75mg daily was used for six weeks along with lifelong aspirin therapy. All patients underwent nimodipine therapy, daily TCD monitoring, and EVD or lumbar drainage as needed. Digital subtraction angiography (DSA) was performed for neurologic deterioration not explained by other causes, and nimodipine used to treat symptomatic vasospasm. Patient condition was dichotomized according to the World Federation of Neurological Societies scale (good: 1-3; poor 4-5), and SAH radiographic severity dichotomized according to the Fisher scale into high (3-4) and low (1-2) grades. The six month functional outcome was classified as favorable if the modified Rankin scale (mRS) was < 3. DCI was defined as new infarcts not visible on pretreatment or early posttreatment (< 48 hours) CT scan. New intracranial hemorrhages were classified as minor (found incidentally on routine imaging) or major (leading to clinical deterioration or requiring surgery). Endpoints included the impact of antiplatelets on risk of DCI and chance of favorable six-month outcome. Secondary endpoints were in-hospital mortality and post-treatment bleeding events.
Five hundred eighty patients were included. Mean age was 55 + 13 years, 67 percent were female, 38 percent presented in poor clinical condition, 74 percent had high radiographic severity and 66 percent required external CSF diversion due to hydrocephalus. Intervention for symptomatic vasospasm was required in 21 percent of patients. Cerebral infarction occurred in 42 percent of patients (26 percent early infarcts, and 22 percent due to DCI). Three hundred twenty-nine (56 percent) patients received aspirin after aneurysm treatment, and 43 (7.4 percent) of these patients underwent stent-assisted coiling requiring dual antiplatelet therapy. There was no difference in the rate of early infarcts between intervention and control groups, but the risk of DCI was significantly lower in the intervention group (p=0.001, OR=0.48, 95% CI 0.32-0.73). The risk of DCI was reduced with use of aspirin in both univariate and multivariate analyses (p < 0.001, adjusted OR=0.41, 95% CI 0.25-0.67). Other factors associated with development of DCI in multivariate analysis included poor WFNS (p=0.008), acute hydrocephalus (p=0.03), vasospasm (p<0.001) and major rebleeding (p<0.001), while high Fisher grade was not associated with DCI. The intervention group had a higher risk for minor bleeding events (5.2 percent versus 1.6 percent), but no increase in major bleeding events (3.6 percent versus 2.4 percent). Administration of aspirin significantly increased the likelihood of six-month favorable outcome as well as decreased mortality in both univariate analysis and multivariate analysis adjusted for age, initial SAH severity and additional administration of clopidogrel. Dual antiplatelet therapy showed no impact on occurrence of DCI compared to aspirin monotherapy (p=0.07) but did increase the risk of major bleeding and was significantly associated with higher in-hospital mortality (p=0.03) and lower favorable outcome (p=0.007). There was no difference in the occurrence of symptomatic vasospasm between intervention and control groups or for mono versus dual antiplatelet therapy.
This study showed that use of aspirin after endovascular aneurysm treatment in SAH is associated with lower rates of delayed cerebral ischemia and better functional outcomes, without an increase in major bleeding events. These results were born out in both univariate and multivariate analyses. Proposed mechanisms include inhibition of thromboxane A2-mediated vasoconstriction, decreased platelet aggregation and intraluminal vessel adhesion, and decreased microthrombosis after SAH. Interestingly, antiplatelet use did not impact occurrence of symptomatic vasospasm despite the decrease in confirmed DCI. This study was limited as it was retrospective and only patients deemed to be at high risk of thromboembolismwere given antiplatelet therapy. This study also has limited generalizability due to exclusion of surgically treated aneurysms; it is unclear if a similar benefit would be seen in these patients, as they are presumably at higher bleeding risk postoperatively. These benefits were not seen with dual antiplatelet therapy, which was associated with higher risk of major bleeding, but caution should be used in interpreting this data as the number of patients who received dual therapy was small. Use of aspirin after aneurysmal SAH appears to be safe and is associated with reduced DCI and better outcomes. A randomized controlled trial is necessary to further elucidate the full benefit of aspirin in aneurysmal SAH patients.
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