Meeting NewsPerspective

Perioperative oral anticoagulant management strategy safe among patients with atrial fibrillation

James D. Douketis, MD, FRCP(C)
James D. Douketis

SAN DIEGO — A procedure for interrupting direct oral anticoagulant therapy in the perioperative setting conferred low rates of bleeding among both low-risk and high-risk patients with atrial fibrillation, according to findings from the prospective PAUSE study presented during the late-breaking abstract session at ASH Annual Meeting and Exposition.

According to the management strategy, patients can safely stop taking direct oral anticoagulants (DOACs) for 1 day before and after procedures with a low risk for bleeding, and for 2 days before and after procedures with a higher bleeding risk.

The management of perioperative anticoagulation is common, applying to one in six patients with atrial fibrillation every year, according to James D. Douketis, MD, FRCP(C), professor in the division of hematology and thromboembolism of the department of medicine at McMaster University in Hamilton, Canada and associate director of the clinical teaching unit at St. Joseph’s Healthcare.

However, since the introduction of DOACs in 2010, there have been few prospective studies of their perioperative management, according to Douketis. Although procedures for stopping other blood thinners such as warfarin are well established, there are little data that pertain to DOACs.

“It’s not surprising there is a lot of variability in clinical practice, and inconsistency around guideline recommendations,” Douketis said during a press conference. “The questions that commissions ask about this problem are: When do you interrupt the DOAC? When do you resume it? Should you be using perioperative bridging anticoagulation? Should you do a blood test to measure the coagulation function before the surgery?”

Douketis and colleagues aimed to establish a standardized DOAC management strategy for patients with atrial fibrillation undergoing elective surgery. Researchers analyses use of the DOACs apixaban (Eliquis; Bristol-Myers Squibb, Pfizer), dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Janssen).

Appropriate management of these patients could prevent thromboembolism and other cardiovascular outcomes, Douketis said.

The current analysis included 3,007 patients (mean age, 72.5 years; 66.1% men) screened at 23 centers in Canada, the U.S. and Europe.

Among them, 1,257 patients were treated with apixaban, 668 with dabigatran and 1,082 with rivaroxaban. Overall, 33.5% were undergoing a high bleeding-risk surgery or procedure.

Researchers tailored the management approach to each drug; however, the common denominator was that patients with low bleeding risk were taken off the drug 1 day before the procedure and 1 day after. For patients with high bleeding risk, the protocol was to stop 2 days before and 2 days after the procedure. Protocols called for no heparin bridging, but patients were able to undergo low-dose heparin as VTE prophylaxis.

Researchers conducted follow-up weekly for 4 weeks postprocedure.

Results showed that arterial thromboembolism occurred in 0.16% (95% CI, 0-0.48) of patients in the apixaban group, 0.6% (95% CI, 0-1.33) of those in the dabigatran group and 0.37% (95% CI, 0-0.82) of those treated with rivaroxaban.

Major bleeding rates were 1.35% (95% CI, 0-2) for apixaban, 0.9% (95% CI, 0-1.73) for dabigatran and 1.85% (95% CI, 0-2.65) for rivaroxaban.

“The rate of major bleeding was about 1%,” Douketis said. “We were able to achieve this outcome with dabigatran, but not quite with apixaban and rivaroxaban.”

Researchers also evaluated residual preoperative DOAC levels in 85% of patients and found that the proportion of high bleed-risk patients with levels less than 50 ng/mL was 98.9%.

Further, researchers observed DOAC levels of less than 30 ng/mL among 93.1% of patients in the apixaban high-risk group, 98.9% of those in the dabigatran high-risk group and 85.3% of those in the rivaroxaban high-risk group.

“In patients with atrial fibrillation who had DOAC interruption for an elective surgery or procedure, a simple, standardized perioperative management strategy that foregoes heparin bridging and pre-operation coagulation testing was associated with low rates of major bleeding and arterial thromboembolism,” Douketis said. “This is the first study to demonstrate the safety of a standardized perioperative management approach for patients with atrial fibrillation who are taking a DOAC. It will have an effect on clinical practice guidelines.” – by Rob Volansky

Reference:

Douketis J, et al. Abstract LBA-5. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosures : Douketis reports consultant/advisory roles with or research funding or honoraria from AstraZeneca, Bayer, Biotie Therapies, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Pfizer, Portola, Sanofi and The Medicines Co. Please see the abstract for all other authors’ relevant financial disclosures.

James D. Douketis, MD, FRCP(C)
James D. Douketis

SAN DIEGO — A procedure for interrupting direct oral anticoagulant therapy in the perioperative setting conferred low rates of bleeding among both low-risk and high-risk patients with atrial fibrillation, according to findings from the prospective PAUSE study presented during the late-breaking abstract session at ASH Annual Meeting and Exposition.

According to the management strategy, patients can safely stop taking direct oral anticoagulants (DOACs) for 1 day before and after procedures with a low risk for bleeding, and for 2 days before and after procedures with a higher bleeding risk.

The management of perioperative anticoagulation is common, applying to one in six patients with atrial fibrillation every year, according to James D. Douketis, MD, FRCP(C), professor in the division of hematology and thromboembolism of the department of medicine at McMaster University in Hamilton, Canada and associate director of the clinical teaching unit at St. Joseph’s Healthcare.

However, since the introduction of DOACs in 2010, there have been few prospective studies of their perioperative management, according to Douketis. Although procedures for stopping other blood thinners such as warfarin are well established, there are little data that pertain to DOACs.

“It’s not surprising there is a lot of variability in clinical practice, and inconsistency around guideline recommendations,” Douketis said during a press conference. “The questions that commissions ask about this problem are: When do you interrupt the DOAC? When do you resume it? Should you be using perioperative bridging anticoagulation? Should you do a blood test to measure the coagulation function before the surgery?”

Douketis and colleagues aimed to establish a standardized DOAC management strategy for patients with atrial fibrillation undergoing elective surgery. Researchers analyses use of the DOACs apixaban (Eliquis; Bristol-Myers Squibb, Pfizer), dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Janssen).

Appropriate management of these patients could prevent thromboembolism and other cardiovascular outcomes, Douketis said.

The current analysis included 3,007 patients (mean age, 72.5 years; 66.1% men) screened at 23 centers in Canada, the U.S. and Europe.

Among them, 1,257 patients were treated with apixaban, 668 with dabigatran and 1,082 with rivaroxaban. Overall, 33.5% were undergoing a high bleeding-risk surgery or procedure.

Researchers tailored the management approach to each drug; however, the common denominator was that patients with low bleeding risk were taken off the drug 1 day before the procedure and 1 day after. For patients with high bleeding risk, the protocol was to stop 2 days before and 2 days after the procedure. Protocols called for no heparin bridging, but patients were able to undergo low-dose heparin as VTE prophylaxis.

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Researchers conducted follow-up weekly for 4 weeks postprocedure.

Results showed that arterial thromboembolism occurred in 0.16% (95% CI, 0-0.48) of patients in the apixaban group, 0.6% (95% CI, 0-1.33) of those in the dabigatran group and 0.37% (95% CI, 0-0.82) of those treated with rivaroxaban.

Major bleeding rates were 1.35% (95% CI, 0-2) for apixaban, 0.9% (95% CI, 0-1.73) for dabigatran and 1.85% (95% CI, 0-2.65) for rivaroxaban.

“The rate of major bleeding was about 1%,” Douketis said. “We were able to achieve this outcome with dabigatran, but not quite with apixaban and rivaroxaban.”

Researchers also evaluated residual preoperative DOAC levels in 85% of patients and found that the proportion of high bleed-risk patients with levels less than 50 ng/mL was 98.9%.

Further, researchers observed DOAC levels of less than 30 ng/mL among 93.1% of patients in the apixaban high-risk group, 98.9% of those in the dabigatran high-risk group and 85.3% of those in the rivaroxaban high-risk group.

“In patients with atrial fibrillation who had DOAC interruption for an elective surgery or procedure, a simple, standardized perioperative management strategy that foregoes heparin bridging and pre-operation coagulation testing was associated with low rates of major bleeding and arterial thromboembolism,” Douketis said. “This is the first study to demonstrate the safety of a standardized perioperative management approach for patients with atrial fibrillation who are taking a DOAC. It will have an effect on clinical practice guidelines.” – by Rob Volansky

Reference:

Douketis J, et al. Abstract LBA-5. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosures : Douketis reports consultant/advisory roles with or research funding or honoraria from AstraZeneca, Bayer, Biotie Therapies, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Pfizer, Portola, Sanofi and The Medicines Co. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective
    Alok A. Khorana

    Alok A. Khorana

    This is a really large and challenging study to do because you’re interrupting patients’ anticoagulants and seeing what happens to them. The researchers followed specific protocols on stopping anticoagulant drugs before the procedure and restarting them after the procedure. There is some conflicting information about exactly when to stop and restart them. Their study seems to clarify and codify that. There are so few thrombotic events like stroke or bleeding after the procedure. I definitely think it’s an important study that should help clinicians manage periprocedural use of anticoagulation.


    • Alok A. Khorana, MD
    • Cleveland Clinic

    Disclosures: Khorana reports personal fees, research funding or nonfinancial travel support from, consultant roles with AngioDynamics, Bayer, Halozyme Therapeutics, Janssen, LEO Pharma, Medscape/WebMD, Parexel, Pfizer, Pharmacyclics, PharmaCyte Biotech, Sanofi, Seattle Genetics, TriSalus Life Sciences.

    Perspective
    Mark Crowther

    Mark Crowther

    Direct oral anticoagulants are a relatively new form of anticoagulant taken in pill form. They are used mostly for patients with atrial fibrillation. Dr. Douketis’s study looks at how you manage these patients around the time of elective surgery. The study suggests that patients can safely stop taking their DOACs in a very organized fashion based on bleeding risk. It will almost instantaneously establish a treatment practice and a treatment standard for a vast number of patients in North America and around the world who take these drugs.

    • Mark Crowther, MD, MSc, FRCPC
    • McMaster University

    Disclosures: Crowther reports a speakers bureau role with Alexion; equity ownership in Alnylam; board of directors or consultant/advisory roles with Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Octapharma Plasma and Shionogi; research funding from Bayer and Leo Pharma; and honoraria from Pfizer.

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