Patients with atrial fibrillation are at a higher risk of stroke and death, a risk that can be greatly reduced with oral anticoagulants (OACs). With several new oral anticoagulants (NOACs) in clinical use, clinicians are faced with different options. The investigators reviewed several pivotal NOAC trials. The following are key points in the selection of OACs for stroke prevention in patients with non-valvular atrial fibrillation (NVAF).
1. Patients with NVAF have a high risk of stroke and death, and this risk can be significantly reduced by oral anticoagulants.
2. 30% of patients with NVAF in the four NOAC pivotal randomized trials had coronary artery disease (CAD). The combination of OAC and antiplatelet agents significantly increases the risk of major bleeding.
a. For patients with NVAF combined with CAD, one NOAC alone is best (for all NOACs). In selected patients, the long-term addition of aspirin remains indicated based on individual risk and coronary anatomy.
b, For patients undergoing PCI and requiring triple antithrombotic therapy (OAC + aspirin + second antiplatelet agent), a well-controlled dose of vitamin K antagonist (TTR > 70%, INR range 2.0-2.5) or choice of NOAC is required.
c. Drug selection for patients with NVAF combined with peripheral arterial disease (PAD) is similar to that for patients with NVAF combined with CAD.
3. For patients with NVAF not treated with adequate OAC, reentry is associated with a 5-7% increased risk of clinical embolic events within 1 month. asymptomatic brain lesions are more common after NVAF ablation (10-15% of patients), but their clinical significance and impact are uncertain.
a. Vitamin K antagonists remain the standard of care for patients with NVAF resuscitation. NOAC has particular advantages in terms of safety and efficacy, and ongoing trials will provide more information on safety and efficacy.
b. Warfarin remains the standard choice for OAC in patients undergoing NVAF ablation. Uninterrupted dabigatran, apixaban, or rivaroxaban may be used as alternatives, and patients on warfarin require bridging with heparin at the time of resuscitation.
4. Patients with implanted mechanical valves or moderate-to-severe rheumatic heart disease mitral stenosis are not candidates for NOAC therapy and should be given a vitamin K antagonist.
a, Patients with other valve abnormalities (e.g., mitral, aortic, tricuspid insufficiency, and aortic stenosis) are safe to use NOAC (especially apixaban or rivaroxaban) or vitamin K antagonists.
5. Patients treated with high-quality vitamin K antagonists (TTR > 70%) are at less risk of thrombosis and bleeding.
a. It is reasonable to continue warfarin therapy in patients with TTR > 70%. Prior complications, high SAMe-TT2R2 scores, or based on individual patient preference, may consider switching warfarin to NOAC.
6. Patients with NVAF in the presence of 1 stroke risk factor (in addition to gender) have a moderate risk of stroke.
a. Patients with 1 stroke risk factor in addition to gender may be considered for OAC treatment based on limited dabigatran or apixaban clinical trial data.
7. NVAF, even if paroxysmal, is usually progressive. Therefore, patients with a first episode of NVAF should be given OAC therapy at the appropriate time with due consideration of stroke risk.
a. The type of NVAF, frequency or number of episodes do not affect OAC selection.
8. There are often activity and metabolic interactions between commonly used antiarrhythmic drugs in combination with vitamin K antagonists, but there are rarely drug interactions with NOAC.
a. Dabigatran or edoxaban need to be reduced in patients taking verapamil, but rivaroxaban or apixaban do not require dose reduction.
b. Dabigatran and dronedarone should not be used in combination. Patients on dronedarone should be given a 30 mg dose if edoxaban is used.
9. Warfarin is superior to aspirin and placebo for secondary prevention of stroke in patients with NVAF, and a meta-analysis showed that NOAC is superior to warfarin.
a. NOAC as a whole was superior to warfarin in the secondary prevention of stroke in patients with NVAF.
b. Aspirin should not be used in the secondary prevention of stroke in patients with NVAF.
c. OAC combined with aspirin does not further prevent major ischemic events compared with OAC alone and should be limited to specific high-risk periods.
10. Anticoagulants are contraindicated in patients receiving thrombolytic therapy for acute ischemic stroke because of the increased risk of cerebral hemorrhage. Laboratory tests can help assess the extent of anticoagulation and the risk of intracranial hemorrhage.
a. After careful risk/benefit discussion, intravenous thrombolytic therapy may be given if coagulation tests with specific NOAC or vitamin K antagonists show low or no anticoagulant strength (off-label).
b. Mechanical thrombolysis may be considered in appropriate patients receiving effective systemic anticoagulation.
11. Patients with NVAF-related ischemic stroke or TIA have an increased risk of embolic recurrence without current anticoagulation and an increased risk of bleeding with initiation of anticoagulation.
a. Anticoagulation with OAC (including NOAC) may be initiated on the first day after neuroimaging has ruled out intracranial hemorrhage in patients with NVAF after the occurrence of a TIA.
b. In patients with NVAF, OAC therapy may be initiated after 3 days in patients with mild stroke, at 5-7 days in patients with moderate stroke, and at 12-14 days in patients with severe stroke.
12. In patients with NVAF, multiple NOACs may increase the risk of gastrointestinal major bleeding compared with warfarin.
a. Apixaban 5 mg bid or dabigatran 110 mg bid is the first choice for stroke prevention in patients at high risk of gastrointestinal bleeding in NVAF.
b. Dabigatran 150 mg bid, edoxaban 60 mg qd and rivaroxaban 20 mg qd are second-line options for patients at high risk of gastrointestinal bleeding.
c. NOAC therapy should be restarted as soon as possible after the occurrence of gastrointestinal bleeding, taking into account safety.
d. Use of antiplatelet agents and age ≥75 years increase the risk of gastrointestinal bleeding.
13. Chronic kidney disease is an important risk factor for stroke and bleeding in patients treated with NVAF anticoagulation. Most NOACs are at least partially cleared by the kidneys, so this group of patients requires adjustment of NOAC dose or avoidance of this class of drugs.
a. For patients with NVAF combined with chronic kidney disease stage III (CrCl 30-49 ml/min), apixaban 2.5-5 mg bid, rivaroxaban 15 mg qd or edoxaban 30 mg qd is preferred
b. For patients with NVAF treated with dialysis, non-anticoagulation or vitamin K antagonist therapy is appropriate and NOAC should be avoided.
c. Edusaban 60 mg qd should not be given to NVAF patients with CrCl > 95 ml/min.
14. The risk of stroke and bleeding increases with age. In older patients with NVAF, there may be a net benefit for patients treated with OAC.
a, Patients aged ≥75 years may choose apixaban 2.5-5 mg bid as first-line therapy. Dabigatran 110 mg bid, rivaroxaban 20 mg qd, or edoxaban 60 mg qd may be alternative options.
15. Adherence is a key factor in the efficacy of OAC in stroke prevention in patients with NVAF.
a. OAC should not be given to patients who are intentionally nonadherent to treatment.
b. It is important to understand the reasons for non-adherence in this group of patients and to develop strategies to improve adherence for effective stroke prevention.