Periprocedural Anticoagulation: Novel Agents, New Rules

Novel anticoagulation agents (eg, dabigatran,¹ rivaroxaban,² apixaban³) are gaining wide acceptance over the vitamin K antagonist warfarin, for their simplicity of use and proven efficacy. At the same time, clinicians continue to navigate the learning curve on patient selection and optimal use.

A common line of questioning from the primary care community revolves around when to discontinue oral anticoagulation with these agents in advance of surgery and invasive procedures, such as colonoscopy and dental work.

The warfarin protocol, in place for decades, calls for a 5-day drug-free interval before any invasive procedure. But the pharmacokinetics of the new agents are radically different^1-3 and a 5-day interruption in treatment could prove lethal.

• How long before an operative procedure should anticoagulation be stopped in patients taking the new factor-Xa and direct-thrombin inhibitors?
• Is therapeutic bridging of any kind required?
• Antidotes are not available for either dabigatran or rivaroxaban; is this a concern?
• What about the newer, more potent antiplatelet agents? What periprocedural intervals do they require?  

Periprocedural Anticoagulation

To answer these questions and put the issue into clinical perspective for primary care physicians, here are Drs Christopher Cannon and Payal Kohli. Dr Cannon, a senior investigator with the TIMI Study Group, is Editor-in-Chief of Cardiosource Science and Quality. He is also Professor of Medicine at Harvard Medical School and Associate Physician in the Cardiovascular Division of Brigham and Women’s Hospital in Boston. Dr Kohli graduated from Harvard Medical School, completed her internal medicine training in Boston, and is currently a fellow in cardiovascular medicine at the University of California San Francisco.

Take-Home Points
• The new oral anticoagulants have been shown to have better safety profiles (lower rates of intracranial hemorrhage) and improved efficacy versus warfarin.
• They are active anticoagulants with half-lives of approximately 12 hours so most are dosed twice daily. Full anticoagulation is reached within approximately 1 hour after dosing, unlike warfarin which requires 4 to 7 days
• Warfarin is usually discontinued 5 days before elective surgical procedures but the novel anticoagulants should be stopped just 2 days in advance.

References:

References
1. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2012.  www.pradaxa.com. Accessed July 5, 2012.
2. Rivaroxaban [package insert].  Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2011. http://www.xarelto-us.com. Accessed July 5, 2012.
3. Bristol-Myers Squibb. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). [2012 July 5]. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00412984?term=ARISTOTLE&rank=1. NLM Identifier: NCT00412984.