Review ArticlesGiovanni Landoni, MDSection Editors?>Management of Direct Oral Anticoagulants in the Perioperative Setting
Section snippets
Direct Oral Anticoagulants: Approved Indications
There are 3 main indications for DOAs: (1) Prophylaxis of venous thrombosis after orthopedic surgery (low dosage), (2) prevention of stroke in patients with nonvalvular AF, and (3) treatment of deep venous thrombosis and/or pulmonary embolism (these 2 last indications with higher dosage). Other indications are still under investigation. For example, low doses of DOAs have been investigated in combination with antiplatelet agents after acute coronary syndromes.1 Consequently, a rapid increase in
Comparison with VKAs and Clinical Relevance for Anesthesiologists
Data from randomized, phase III trials of the DOAs indicate that these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism in patients with AF.4, 5, 6, 7 Several meta-analyses have drawn the same conclusions: A favorable risk-benefit profile with significant reductions in stroke, intracranial hemorrhage, and mortality and with similar major bleeding as for warfarin but with increased gastrointestinal bleeding.8, 9, 10
Recent data have shown that around
Major Complications and Pitfalls Experienced in the Literature
A few months after FDA approval of dabigatran for stroke prevention in nonvalvular AF (October 2010), a French team raised concerns on dabigatran administration in elderly patients in 2 cases, including 1 fatal.24 These 2 cases highlighted the necessity of caution when treating “borderline” patients: Low body weight, very old age, and altered renal function. It is crucial when they are considered for invasive procedures.
Until the present time, 2 large registries have been published with
Pharmacokinetic Properties of the DOAs
A complete review of pharmacokinetics of DOAs is beyond the scope of this article. Still, as all physicians, anesthesiologists must know of the main properties of these agents and their differences with VKAs in order to optimize the peri-procedural management of such patients.20, 22, 23, 28, 29 The main features of pharmacokinetics of the DOAs are summarized in Table 1, and the main differences with VKAs are shown in Table 2. These differences have important clinical implications.
Even though
When to Test?
Unlike with VKAs, clinical trials with the DOAs suggested that they do not need laboratory testing for dose adjustment, as they have predictable pharmacokinetics.23, 28, 33 Nevertheless, the measurement of their anticoagulant effect may be useful in many clinical circumstances including the preoperative setting, adverse event (hemorrhage or thrombosis), and chronic renal insufficiency (Table 3).
Recently, the absence of dose-adjustment requirement has been partly questioned by data extracted
Practical Guidelines
Perioperative management of anticoagulant therapy is a complex topic that must weigh the risk of thromboembolism and stroke against the risk of surgical bleeding. The former may be assessed by the existence of risk factors for stroke or other thromboembolic events; the assessment of the latter comes from a combination of surgical and patient-specific factors.
Conclusion
DOAs offer several advantages compared with VKA, and an increased use of these drugs is expected, especially in patients with atrial fibrillation.47 However, important issues must be acknowledged by anesthesiologists for optimal perioperative patient care. The application of current recommendations about perioperative management of DOAs, or severe bleeding under these treatments, mandatory to improve outcome of these patients. In the near future, the availability of specific antidotes, the
References (47)
- et al.
Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients
Am Heart J
(2011) - et al.
Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation
Chest
(2010) - et al.
A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The Euro Heart Survey
Chest
(2010) - et al.
Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF)
Am Heart J
(2006) Use of novel oral anticoagulants for patients with atrial fibrillation: systematic review and clinical implications.
Heart Lung
(2014)- et al.
Periprocedural management of oral anticoagulation in patients with atrial fibrillation: Approach in the era of new oral anticoagulants
Can J Cardiol
(2013) - et al.
[Atrial fibrillation: from cardiology to perioperative management]
Ann Fr Anesth Reanim
(2012) - et al.
Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
Chest
(2012) - et al.
[Surgery and invasive procedures in patients on long-term treatment with oral direct thrombin or factor Xa inhibitors]
Ann Fr Anesth Reanim
(2011) - et al.
Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: Analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation)
J Am Coll Cardiol
(2013)