Warfarin Ups Trauma Mortality Risk More Than Other Drugs

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.

DETROIT – Preinjury use of warfarin, but not aspirin or clopidogrel, significantly increased the risk of death in a retrospective analysis of 3,488 trauma patients.

Overall, mortality was 13.6% for patients on warfarin (Coumadin), aspirin, clopidogrel (Plavix), or various combinations, compared with 6.2% for patients not on these medications.

When mortality data were broken down by drug, warfarin demonstrated a mortality of 24% vs. 6% for controls.

After they adjusted for the potential confounders of age and injury severity score, the researchers found that the relative risk of a patient on warfarin dying during hospitalization as a result of their injury remained significant at 3.9, first-year resident Dr. Travis Arnold reported on behalf of his colleagues and lead author Dr. Carrie Jahraus at Albany (N.Y.) Medical College.

Surprisingly, aspirin and clopidogrel were not significantly associated with increased mortality at 12.3% and 9.3%, respectively, when adjusted for confounders.

"With aspirin and, [perhaps] clopidogrel, there may be some protective mechanism that we don’t fully understand," senior author Dr. Daniel Bonville said in an interview, adding that other groups have found similar results for the two agents.

All of the drugs increased the risk of intracranial hemorrhage when compared with controls (50% vs. 30%). The adjusted relative risk was 3.2 for warfarin, 1.9 for patients on warfarin plus clopidogrel, and 1.6 for those on aspirin or other combinations.

A total of 3,488 trauma patients were identified in the Albany Medical College database from September 2004 to December 2007. Of these, 456 patients were on some form of anticoagulation or antiplatelet therapy including 91 patients on warfarin alone, 228 on aspirin, 43 on clopidogrel, and 94 on various combinations. The mean warfarin international normalized ratio (INR) level was within the therapeutic window at 2.4, with 95% of patients falling between 2.2 and 2.6, Dr. Arnold said.

The percentage of patients in the treatment and control groups who experienced a blunt trauma was similar at 99% vs. 93%, respectively, as was the percentage with Injury Severity Scores greater than 15 (55% vs. 50%, respectively).

Hospital length of stay greater than 10 days was similar at 30% for the treatment group vs. 24% for controls, and remained similar after adjustment, Dr. Arnold said.

The percentage of patients discharged to home was significantly lower at 48% among patients on warfarin and antiplatelet agents vs. 74% for controls (P less than .01). This difference disappeared when adjusted for age.

When the researchers compared the subgroup of 191 patients who had intracranial hemorrhage with controls, only warfarin increased mortality (29% vs. 6%, adjusted RR 3.1) and the need for craniotomy (15% vs. 7%, adjusted RR 2.2), Dr. Arnold said.

He concluded that warfarin continues to be a necessary evil for many patients with coronary artery disease or history of stroke and advocated for greater patient education by primary care providers on the risks of anticoagulants.

Invited discussant Dr. Mark Hemmila, with the University of Michigan, Ann Arbor, said it is fortunate that only warfarin increases the risk of mortality given how difficult it is to reverse the effects of aspirin and clopidogrel, but that he would rank clopidogrel ahead of Coumadin and aspirin in terms of dangerousness. He asked Dr. Arnold to speculate on why no effect was observed and how the researchers recommend evaluating patients on warfarin.

Dr. Arnold said if a patient is on warfarin and has significant trauma and an elevated INR, warfarin reversal is initiated prior to obtaining computed tomography imaging. Factor VII is used, although they are transitioning more to the prothrombin complex. He said it is unclear why no impact on mortality was observed for aspirin given the large number of aspirin users in the study and that an effect would likely have been observed had there been more clopidogrel patients.

A recent analysis of 1.2 million patients in the American College of Surgeons’ National Trauma Data Bank reported that warfarin was associated with an increased risk of death, regardless of type of injury, indication for anticoagulation, or comorbidities. In all, 9.3% of warfarin-users died from their injuries vs. 4.8% of nonusers (Arch. Surg. 2011 [doi:10.1001/archsurg.2010.313]).

The researchers disclosed no conflicts of interest.