Post-treatment Antiplatelet Therapy Reduces Risk for Delayed Cerebral Ischemia due to Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series. OBJECTIVE To analyze the benefit/risk profile of antiplatelet use in SAH patients. METHODS This retrospective case-control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale < 3) were compared in both groups. RESULTS Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P < .001, adjusted odds ratio = 0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P = .02, adjusted odds ratio = 1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P = .02 vs P = .51 for major bleeding events). CONCLUSION Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.

[1]  J. Broderick,et al.  Dual antiplatelet therapy in aneurysmal subarachnoid hemorrhage: association with reduced risk of clinical vasospasm and delayed cerebral ischemia. , 2017, Journal of neurosurgery.

[2]  P. Goodney,et al.  A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery , 2018, Annals of surgery.

[3]  F. Testai,et al.  Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: Beyond Vasospasm and Towards a Multifactorial Pathophysiology , 2017, Current Atherosclerosis Reports.

[4]  V. Seifert,et al.  Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional ‘H’ therapy in vasospasm treatment , 2017, Journal of NeuroInterventional Surgery.

[5]  P. Chen,et al.  Antiplatelet therapy for the prevention of peri-coiling thromboembolism in high-risk patients with ruptured intracranial aneurysms. , 2017, Journal of Neurosurgery.

[6]  S. Mayer,et al.  Management of delayed cerebral ischemia after subarachnoid hemorrhage , 2016, Critical Care.

[7]  B. Foreman The Pathophysiology of Delayed Cerebral Ischemia , 2016, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[8]  K. Kaier,et al.  Early Identification of Individuals at High Risk for Cerebral Infarction after Aneurysmal Subarachnoid Hemorrhage: The BEHAVIOR Score , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  J. Weinberger Adverse Effects and Drug Interactions of Antithrombotic Agents Used in Prevention of Ischaemic Stroke , 2012, Drugs.

[10]  A. Algra,et al.  Occurrence and impact of delayed cerebral ischemia after coiling and after clipping in the International Subarachnoid Aneurysm Trial (ISAT) , 2011, Journal of Neurology.

[11]  J. Bugnicourt,et al.  Aspirin non-responder status and early neurological deterioration: A prospective study , 2011, Clinical Neurology and Neurosurgery.

[12]  C. Woernle,et al.  Do iatrogenic factors bias the placement of external ventricular catheters?--a single institute experience and review of the literature. , 2011, Neurologia medico-chirurgica.

[13]  Joseph P Broderick,et al.  Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies: Proposal of a Multidisciplinary Research Group , 2010, Stroke.

[14]  J. Simard,et al.  Unfractionated Heparin: Multitargeted Therapy for Delayed Neurological Deficits Induced by Subarachnoid Hemorrhage , 2010, Neurocritical care.

[15]  R. Tamargo,et al.  Inflammation and cerebral vasospasm after subarachnoid hemorrhage. , 2010, Neurosurgery clinics of North America.

[16]  R. Tamargo,et al.  Role of inflammation (leukocyte-endothelial cell interactions) in vasospasm after subarachnoid hemorrhage. , 2010, World neurosurgery.

[17]  A. Algra,et al.  Effect of Antiplatelet Therapy for Endovascular Coiling in Aneurysmal Subarachnoid Hemorrhage , 2009, Stroke.

[18]  Isabel Wanke,et al.  Stents for intracranial wide-necked aneurysms: more than mechanical protection , 2008, Neuroradiology.

[19]  M. Oh,et al.  Accuracy of the freehand pass technique for ventriculostomy catheter placement: retrospective assessment using computed tomography scans. , 2008, Journal of neurosurgery.

[20]  W. M. van den Bergh,et al.  Antiplatelet therapy for aneurysmal subarachnoid haemorrhage. , 2007, The Cochrane database of systematic reviews.

[21]  D. Graham,et al.  Thromboembolism and Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: An Autopsy Study , 2006, Neurosurgery.

[22]  G. Gallia,et al.  Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage , 2006, Neurological research.

[23]  M. Korinth Low-dose aspirin before intracranial surgery – results of a survey among neurosurgeons in Germany , 2006, Acta Neurochirurgica.

[24]  W. M. van den Bergh,et al.  Randomized Controlled Trial of Acetylsalicylic Acid in Aneurysmal Subarachnoid Hemorrhage: The MASH Study , 2006, Stroke.

[25]  D. Nichols,et al.  Influence of aspirin on outcome following aneurysmal subarachnoid hemorrhage. , 2004, Journal of neurosurgery.

[26]  H. Diener,et al.  Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial , 2004, The Lancet.

[27]  A. Algra,et al.  Antiplatelet therapy in aneurysmal subarachnoid hemorrhage: a systematic review. , 2003, Stroke.

[28]  J. Vane,et al.  The mechanism of action of aspirin. , 2003, Thrombosis research.

[29]  S. Yusuf,et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. , 2001, The New England journal of medicine.

[30]  A. Algra,et al.  Rebleeding, secondary ischemia, and timing of operation in patients with subarachnoid hemorrhage , 2000, Neurology.

[31]  A. Algra,et al.  Randomized pilot trial of postoperative aspirin in subarachnoid hemorrhage , 2000, Neurology.

[32]  I. Calder,et al.  Low‐dose aspirin and intracranial surgery A survey of the opinions of consultant neuroanaesthetists in the UK , 1997, Anaesthesia.

[33]  S. Juvela Aspirin and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. , 1995, Journal of neurosurgery.

[34]  S. Haines Postoperative hematoma. , 1995, Journal of neurosurgery.

[35]  C. Patrono Aspirin as an antiplatelet drug. , 1994, The New England journal of medicine.

[36]  H. Ohkuma,et al.  Impairment of Anti‐Platelet‐Aggregating Activity of Endothelial Cells After Experimental Subarachnoid Hemorrhage , 1993, Stroke.

[37]  H. Ohkuma,et al.  Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. , 1991, Stroke.

[38]  M. Kaste,et al.  Platelet thromboxane release and delayed cerebral ischemia in patients with subarachnoid hemorrhage. , 1991, Journal of neurosurgery.

[39]  T. Iwabuchi,et al.  Cerebral microthrombosis in symptomatic cerebral vasospasm--a quantitative histological study in autopsy cases. , 1990, Neurologia medico-chirurgica.

[40]  J. M. Findlay,et al.  Arterial wall changes in cerebral vasospasm. , 1989, Neurosurgery.

[41]  G. Teasdale,et al.  A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[42]  H. Schouten,et al.  Interobserver agreement for the assessment of handicap in stroke patients. , 1988, Stroke.

[43]  Fisher Cm,et al.  Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. , 1980, Neurosurgery.

[44]  J. Oates,et al.  Cerebral Arterial Smooth Muscle Contraction by Thromboxane A2 , 1977, Stroke.