Evaluation of the Risk of Clinically Significant Bleeding with

1
Evaluation of the Risk of Clinically Significant
Bleeding with Aspirin and Warfarin Use in
Patients with Atrial Fibrillation/Flutter John
Bossaer, PharmD Larissa Hall, PharmD Jason
Haney, PharmD Julie Heh, PharmD Karla Hinds,
PharmD Cary Mountjoy, PharmD Kelli
Garrison, PharmD, BCPS Sarah Shrader, PharmD,
BCPS MUSC Medical Center/College of Pharmacy
Residency Program Charleston, SC

• Preliminary Results
• 75 patients meeting inclusion criteria have been
  evaluated to date
• Patients demographics are listed in Table 2
• Clinical service managing warfarin therapy could
  only be identified in 50 of patients (Table 2)
• 69 of patients were receiving low dose aspirin
  (Figure 1)
• Bleeding was documented in 29 patients (39)
• 14 were classified as major bleeds
• 24 were classified as minor bleeds
• 62 were classified as minimal bleeds
• 93 had a documented indication for aspirin
  therapy (Table 3)
• In patients with a hospitalization due to
  bleeding, 15 (52) patients had an INR lt 1.5
  (Figure 2)
• At this time, there appears to be no correlation
  between severity of bleeding and INR on admission

• Background
• The use of concomitant aspirin and warfarin is
  indicated only for patients with mechanical heart
  valves. However, many patients without
  mechanical heart valves receive both aspirin and
  warfarin.
• A recent meta-analysis was published where the
  authors concluded that using both aspirin and
  warfarin was associated with an increased risk of
  bleeding OR 1.43 compared with warfarin
  alone.1
• Although there was no difference in all cause
  mortality, the concomitant use of aspirin and
  warfarin in patients with atrial
  fibrillation/flutter may represent an unnecessary
  risk in patients without a mechanical prosthetic
  heart valve.

•  Purpose
• To evaluate the use of aspirin and warfarin in
  patients with atrial fibrillation/flutter who
  received care within the outpatient clinics at an
  academic medical center.

• Limitations
• Retrospective chart review was dependent on
  reliable documentation
• Not all ICD-9 codes were correct
• Based on the bleeding definitions, it is
  difficult to classify a bleeding category if the
  hemoglobin/hematocrit were not documented
• Bleeding definitions that factor in clinical
  status could alter results
• Multiple assumptions were made, including INR
  goal (if not documented) and categorizing events
  as minimal bleeding if there was no available
  hemoglobin or hematocrit
• Concurrent nonsteroidal anti-inflammatory
  medications were not an exclusion criteria

•  Methods
• Patients with atrial fibrillation/flutter taking
  warfarin and aspirin and receiving care in MUSC
  outpatient clinics from August 31, 2005 to August
  31, 2007 were randomized to be included in the
  study.
• Exclusion criteria included the following
• Age less than 18 years
• Concurrent medications that would increase the
  risk of bleeding
• No International Normalized Ratio (INR) assessed
  in the previous 2 months prior to bleeding event
• Bleeding events will be assessed using the
  Thrombolysis in Myocardial Infarction (TIMI)
  criteria as summarized in Table 1.
• Additional patient data were collected to
  characterize the risk of bleeding and include the
  following
• Use of anti-platelet medications
• Gastrointestinal acid suppression therapy
• INR values
• Percent of INR values within goal range during
  the study period
• Patient demographic data and other variables of
  interest will be summarized with descriptive
  statistics.
• This review was approved by the institutional
  review board.

Conclusions The concomitant use of warfarin and
aspirin represents a gray area of clinical
practice. The majority of patients had a
documented indication for aspirin therapy. As
data collection continues, trends associated with
an increased risk of bleeding may appear.

• Reference
• Dentali F, Douketis JD, Lim w, Crowther M.
  Combined aspirin-oral anticoagulant therapy
  compared with oral anticoagulant therapy alone
  among patients at risk for cardiovascular
  disease a meta-analysis of randomized trials.
  Arch Intern Med 2007167117-24.