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Safety of Perioperative Aspirin Use in Pancreatic SurgeryAndrea M Wolf, Jordan M Winter, Salil D Gabale, Eugene P Kennedy, Ernest L Rosato, Harish Lavu, Charles J Yeo
4 October 2012
Disclosures
• The authors have no financial interests to disclose
Background
• Cardiovascular disease is the number one cause of death in the U.S.
– 900,000 deaths annually
• Aspirin reduces the risk of thrombotic events
– Most widely used anticoagulant
– Recommended by USPSTF for primary prevention of cardiovascular disease and secondary prevention in those patients with risk factors
Platelet Activation and Aggregation
Platelet Activation and Aggregation
• Requires conversion of arachidonic acid to prostaglandin by prostaglandin synthase (cyclooxygenase)
• Prostaglandin is further metabolized by thromboxane synthase to thromboxane A2
(TXA2)
• TXA2 activates new platelets, stimulates aggregation, and enhances vasoconstriction
Thromboxane synthase PG
Cyclooxygenase
TXA2
AA
Platelet activation
Platelet aggregation
Vasoconstriction
Platelet Activation and Aggregation
• Requires conversion of dietary arachidonic acid to prostaglandin by prostaglandin synthase (cyclooxygenase)
• Prostaglandin is further metabolized by thromboxane synthase to thromboxane A2
(TXA2)
• TXA2 activates new platelets, stimulates aggregation, and enhances vasoconstriction
Thromboxane synthase PG
Aspirin
Cyclooxygenase
TXA2
AA
Platelet activation
Platelet aggregation
Vasoconstriction
Aspirin Effect
• Irreversible inhibition of cyclooxygenase
– Occurs within 30 minutes of ingestion
– Lasts for lifespan of platelet, 8 – 10 days
• Studies involving cardiovascular procedures
– Significant decrease in risk of major cardio and cerebrovascular complications and 30-day mortality
Aspirin Withdrawl Syndrome
• Normal hemostasis may return within 72 – 96 hours after discontinuation.
• Rebound period after acute aspirin withdrawl is associated with increased thromboxane production and decreased fibrinolysis
– Clinically prothrombotic state
• Peak in thromboxane levels and cardiovascular events at 8.5 – 10 days post cessation
• Standard practice of discontinuing aspirin 7-10 days preoperatively results in surgery and catecholamine surges timed with the thromboxane peak
Hypothesis
• Continuation of aspirin therapy during pancreatic surgery does not contribute to increases in adverse events
Methods
• Retrospective analysis of an institutional IRB-approved pancreatectomy database
– October 2005 to February 2012
– 1044 patients
• 1017 evaluable subjects after exclusion criteria met
• Records queried for perioperative aspirin use
– Aspirin continued through morning of surgery
– Aspirin resumed orally on post-operative day 1
– 5000 Units of heparin subcutaneously 1 hr prior to incision
Results: Patient Demographics
All patients
(n=1017)
Aspirin users
(n=289, 28%)
Aspirin non-users
(n=728, 72%)
P-value
Age (yr), median
(range)
65
(18-92)
69
(40-87)
62
(18-92)
<0.001
Male gender, n (%) 480 (47) 173 (60) 307 (42) <0.001
Pancreatico-
duodenectomy, n
(%)
686 (68) 204 (30) 482 (70) 0.262
Results: Intraoperative Parameters
All
patients
(n=1017)
Aspirin users
(n=289)
Aspirin non-
users (n=728)
P-value
Estimated blood loss,
median (range)
400
(0-25000)
400
(25-25000)
400
(0-8400)
0.661
Intraoperative crystalloid
(L), median (range)
6.8 (1-28) 6.8 (1-28) 6.8 (1.8-18.2) 0.680
Transfused units, median
(range)
0 (0-36) 0 (0-36) 0 (0-5) 0.221
Results: Complications
All patients
(n=1017)
Aspirin users
(n=289)
Aspirin non-
users (n=728)
P-value
Any complication (%) 43 47 42 0.141
Pancreatic fistula (%) 14 15 14 0.490
Delayed gastric
emptying (%)
9 10 9 0.502
Cardiac complication (%) 9 11 8 0.072
Results: Outcome
All patients
(n=1017)
Aspirin users
(n=289)
Aspirin non-
users (n=728)
P-value
30-day mortality (%) 1 2 1 0.071
Hospital stay (d), median
(range)
6 7
(4-55)
6
(3-62)
0.111
Readmission (%) 16 17 15 0.451
Results
• Comparable blood loss, intraoperative fluids, and transfusion rates
• No difference in overall perioperative complications
• Trend toward more cardiac complications in aspirin use group, but not reaching statistical significance
Limitations
• Retrospective, non-randomized
• Lack of data on preoperative comorbidity
• Patient self-reporting of aspirin use
Discussion
• The small increase in CV events in patients on aspirin therapy was not unanticipated.
• Investigations of patients undergoing cardiovascular procedures show that patients should not discontinue aspirin therapy.
• No negative effects from continued aspirin use were seen in our retrospective analysis of >1000 patients undergoing major pancreatic resection.
• The general practice of discontinuing aspirin therapy should be abandoned unless risk of bleeding outweighs risk of cardiovascular complication.
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