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.