Perioperative Aspirin Use in Patients Undergoing Craniotomy for Brain Tumor

Lauren L Donnangelo BS, Mustafa M Ahmed MD, Dan Neal MS, Kiran Mogali MD, Matthew Decker MD, Maryam Rahman MD, MS

Departments of Neurological Surgery & Cardiology, University of Florida College of Medicine, Gainesville, FL

Abstract Many patients are on antiplatelet agents that are withheld prior to elective neurosurgical procedures to reduce bleeding

risk. Cessation of aspirin in patients with cardiovascular disease is associated with a known increased risk of

thrombotic events, especially in patients with coronary stents. The purpose of this study is to evaluate the safety of

continuing aspirin in patients undergoing brain tumor resection.

The medical records of patients who underwent surgical resection of a brain tumor at the University of Florida

from 2010 to 2014 were evaluated. The patients were separated into groups based on preoperative aspirin use and

whether or not it was stopped prior to surgery. Patients were evaluated for bleeding complications, need for

reoperation, perioperative thrombotic complications, length of hospital stay, and discharge disposition.

Of the 452 patients analyzed, 369 patients were not on chronic aspirin therapy, 55 patients had their aspirin

discontinued prior to surgery, and 28 patients were continued on aspirin perioperatively. There were no statistical

differences detected between the groups for postoperative hematoma (p=1), need for reoperation (p=1), and discharge

disposition (p=1). There was a trend for patients on perioperative aspirin to have increased estimated blood loss

(p=0.12), but these findings did not reach statistical significance.

In this analysis, perioperative low dose aspirin use was not associated with increased risk of perioperative

complications although this needs to be studied prospectively.

Introduction The management of anti-platelet agents is a serious therapeutic dilemma in neurosurgical patients. The devastating

and potentially fatal sequelae of a hemorrhagic complication from a craniotomy are well-known (1). Therefore, most

neurosurgeons commonly stop all anti-platelet agents several days prior to elective cranial surgery. An increasing

number of patients are taking chronic low dose aspirin since aspirin has been shown to have clear benefit in secondary

prevention of cardiovascular events and possible benefit in primary prevention as well (2, 3, 4). Additionally, patients

with coronary stents are often on dual anti-platelet therapy with aspirin and another agent. The ACC/AHA guidelines

recommend uninterrupted dual anti-platelet therapy with aspirin plus a thienopyridine (clopidogrel, prasugrel, or

ticagrelor) for 6 weeks after bare metal stent placement and 12 months after drug-eluting stent placement to prevent

stent thrombosis. Thereafter, aspirin should be continued lifelong in most cases to prevent late stent thrombosis (5).

In most cases, patients with brain tumors need timely surgical treatment that cannot be delayed to meet these anti-

platelet guidelines. If anti-platelet therapy is continued during surgery, the risk of a hemorrhagic complication may

increase (6, 7). Of patients who suffer a postoperative hemorrhage, over half will die or live with severe disability (6).

Therefore, almost uniformly, brain tumor patients on aspirin will have their aspirin stopped prior to surgical resection.

This strategy potentially decreases the risk of post-operative hemorrhage, but increases the risk of thrombotic

cardiovascular events. Currently, little evidence exists to inform the management of neurosurgical patients on

antiplatelet agents.

Quantifying the risks associated with continuing or discontinuing antiplatelet agents in the perioperative period is

critical. The purpose of this study is to evaluate the safety of continuing aspirin in patients undergoing brain tumor

resection by comparing outcomes in patients who were kept on aspirin perioperatively to patients whose aspirin was

discontinued prior to surgery.

References (1) Morgenstern LB, Frankowski RF, Shedden P, Pasteur W, Grotta JC: Surgical treatment for intracerebral hemorrhage (STICH): a single-center,

randomized clinical trial. Neurology 51:1359-1363, 1998

(2) Enomoto Y, Yoshimura S, Sakai N, Egashira Y, Investigators JRoNT: Current perioperative management of anticoagulant and antiplatelet use in

neuroendovascular therapy: analysis of JR-NET1 and 2. Neurol Med Chir (Tokyo) 54:9-16, 2014

(3) Gentilomo C, Huang YS, Raffini L: Significant increase in clopidogrel use across U.S. children's hospitals. Pediatr Cardiol 32:167-175, 2011

(4) Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al: Aspirin in the primary and secondary prevention of vascular disease:

collaborative meta-analysis of individual participant data from randomised trials. Lancet 373:1849-1860, 2009

(5) Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al: 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary

Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the

Society for Cardiovascular Angiography and Interventions. Circulation 124:e574-651, 2011

(6) Palmer JD, Sparrow OC, Iannotti F: Postoperative hematoma: a 5-year survey and identification of avoidable risk factors. Neurosurgery 35:1061-

1064; discussion 1064-1065, 1994

(7) Burger W, Chemnitius JM, Kneissl GD, Rucker G: Low-dose aspirin for secondary cardiovascular prevention - cardiovascular risks after its

perioperative withdrawal versus bleeding risks with its continuation - review and meta-analysis. Journal of Internal Medicine 257:399-414, 2005

Conclusions In this study, continuing aspirin at the time of craniotomy was not associated with increased risk of

postoperative complication such as increased EBL, LOS, RTOR, postoperative hematoma, or thrombosis.

Decisions regarding antiplatelet therapy in the perioperative period would be best made in a multi-disciplinary

fashion, including consultation with a cardiologist. Additionally, tailored therapy with the use of point of care

platelet functional assays may help guide these decisions.

This study provides preliminary data warranting additional investigation in this area in a prospective fashion.

As the number of patients chronically medicating with aspirin continues to rise, it will become increasingly

necessary for neurosurgeons to manage the risks associated with aspirin management in the perioperative

period.

Results 452 brain tumor patients met the inclusion criteria. Of these patients, 369 were not on aspirin therapy, 55 had their

aspirin discontinued prior to surgery, and 28 patients had their aspirin continued in the perioperative period. Not

surprisingly, patients on aspirin were more likely to be older, male, and have more comorbidities compared to patients

not on aspirin. Overall, there was no significant difference between patients who had their aspirin continued or

discontinued prior to surgery. The median dose of aspirin was 81mg in all aspirin groups. A small number of patients

were also on other antiplatelet agents or anticoagulants. These medications were stopped prior to surgery in all

instances. The two groups of patients who had their aspirin discontinued were also not significantly different in

demographics or comorbidities.

The patients were evaluated for incidence of postoperative complications based on perioperative aspirin management.

No statistically significant difference was found in estimated blood loss (EBL) (Figure 1) or postoperative complications

such as postoperative hematoma, return to operating room (RTOR), or thrombotic events (myocardial infarction,

venous thromboembolism or stroke) (Figure 2) in patients whose aspirin was continued versus discontinued. Hospital

length of stay (LOS) and discharge disposition were also similar in all groups (Figures 3 & 4). Discontinued R/M

patients did have a trend toward increased LOS as compared to the Continued and Discontinued R/F patients, but this

likely represents different practice patterns of the surgeons.

Figure 3. Hospital length of stay based on perioperative aspirin

management.

Statistical analysis

R statistical software package (V.3.0.2) used to calculate descriptive statistics and test for associations between each covariate and aspirin status. Fisher’s exact test compared aspirin groups on categorical variables

and the Kruskal-Wallis test compared groups on continuous variables. For comparison of continued and discontinued aspirin, the Mann-Whitney test compared groups on continuous variables. Statistical significance

was determined by p < 0.05.

Figure 1. Operative estimated blood loss based on perioperative

aspirin management.

Figure 2. Adverse events based on perioperative aspirin

management.

Figure 4. Discharge disposition based on perioperative aspirin

management.

Methods

UF IRB-O1 approval obtained

Supra- or infra-tentorial craniotomy for tumor or meningioma at UF Health from 2010-2014

identified via the Neurosurgery Billing Database

ICD-9 codes: 191.0-.9, 225.0-.2, 225.9, 198.3, 192.1, 239.6, 237.1, 237.5-.6, 227.3-.4

CPT codes: 61510, 61512, 61518, 61519

Retrospective chart review conducted using EPIC electronic medical record

n = 452

Primary endpoints: thrombotic complications (myocardial infarction, pulmonary embolism, deep vein thrombosis, or ischemic stroke), postoperative hemorrhage, estimated blood loss (EBL), and length of hospital

stay (LOS). Other collected variables included age, gender, specific pathologic diagnosis, comorbidities (as per the Charlson Comorbidity Index), vital status, date of tumor resection surgery and/or cardiac stent

placement, discharge disposition (home, subacute nursing home, acute rehabilitation facility, correctional facility, or death), reason for reoperation (if applicable), details of other perioperative anticoagulant or

antiplatelet use, and history of pulmonary embolism, deep vein thrombosis, stroke, coronary artery bypass graft, cardiac stent placement, peripheral vascular disease, and coronary artery disease.

Surgeons R/F

n = 55

Surgeons R/M

n = 28

Continue

ASA

n = 28

Discontinue

ASA

n = 27

No ASA

n = 369

Discontinue

ASA

n = 28