Direct oral anticoagulant use in nonvalvular atrial fibrillation with valvular heart disease: a systematic review

Abstract

Direct oral anticoagulants (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), which, according to the American College of Cardiology/American Heart Association/Heart Rhythm Society atrial fibrillation (AF) guidelines, excludes patients with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. However, the data regarding use of DOACs in AF patients with other types of valvular heart disease (VHD) are unclear. We aimed to summarize and evaluate the literature regarding the safety and efficacy of DOAC use in NVAF patients with other types of VHD. After an extensive literature search, a total of 1 prospective controlled trial, 4 subanalyses, and 1 abstract were identified. Efficacy of the DOAC agents in NVAF patients with VHD mirrored the overall trial results. Bleeding risk was significantly increased in VHD patients treated with rivaroxaban, but not for dabigatran or apixaban. Of the bioprosthetic valve patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, no safety or efficacy concerns were identified. In conclusion, subanalyses of DOAC landmark AF trials revealed that dabigatran, rivaroxaban, and apixaban may be safely used in AF patients with certain types of VHD: aortic stenosis, aortic regurgitation, and mitral regurgitation. More evidence is needed before routinely recommending these agents for patients with bioprosthetic valves or mild mitral stenosis. Patients with moderate to severe mitral stenosis or mechanical valves should continue to receive warfarin, as these patients were excluded from all landmark AF trials.

Thromboembolic and bleeding outcomes in patients with atrial fibrillation and valvular heart disease: A descriptive nationwide cohort study

“…Several studies have examined the effectiveness and safety of NOAC vs warfarin in AF patients with VHD, primarily in patients with EHRA Type 2 VHD 25‐32 . Meta‐analyses of post hoc analyses of previous randomised trials examining NOAC vs warfarin in AF patients with VHD showed that when pooling the results there was a reduced risk of thromboembolism in the NOAC group and no difference in the risk of major bleeding 33‐36 . However, in several comparative analyses based on real‐world data, the benefits of NOAC compared with warfarin were inconsistent 25‐28,32 .…”

Real‐world incidence of efficacy and safety outcomes in patients on direct oral anticoagulants with left ventricular systolic dysfunction at a tertiary referral center

“…[2][3][4] Large randomized controlled trials (RCTs) and systematic reviews investigating have shown that DOAC therapy is not inferior to warfarin in the prevention of stroke and systemic embolism, and that it significantly reduces hemorrhagic complications, especially intracranial hemorrhage (ICH) in patients with nonvalvular AF. [5][6][7][8][9][10] In subgroup analyses of LVSD patients in the RE-LY (dabigatran), ROCKET-AF (rivaroxaban), and ARISTOTLE (apixaban) trials, researchers found similar results, with no significant difference between HF patients with preserved or reduced ejection fractions. [11][12][13] However, these RCTs excluded many patients that we often see in actual medical practice, including patients on anticoagulation therapy for indications other than AF, patients with significant renal dysfunction, and patients with a history of gastrointestinal (GI) bleeding and anemia, valvular heart disease, and indications for anticoagulation besides AF.…”

“…Patients with left ventricular systolic dysfunction (LVSD) often have other comorbid conditions that lead to an increased risk of stroke, including atrial fibrillation (AF), which itself is an indication for long‐term anticoagulation . Large randomized controlled trials (RCTs) and systematic reviews investigating direct oral anticoagulants (DOACs), such as the Randomized Evaluation of Long‐Term Anticoagulation Therapy (RE‐LY), Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE), Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET‐AF), and Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48 (ENGAGE AF‐TIMI 48) trials, have shown that DOAC therapy is not inferior to warfarin in the prevention of stroke and systemic embolism, and that it significantly reduces hemorrhagic complications, especially intracranial hemorrhage (ICH) in patients with nonvalvular AF . In subgroup analyses of LVSD patients in the RE‐LY (dabigatran), ROCKET‐AF (rivaroxaban), and ARISTOTLE (apixaban) trials, researchers found similar results, with no significant difference between HF patients with preserved or reduced ejection fractions …”

Anticoagulation in sub‐Saharan Africa: Are direct oral anticoagulants the answer? A review of lessons learnt from warfarin

“…48,50 Fortunately, subgroup analyses of the trial participants of the 4 major Phase III trials comparing warfarin to DOACs found that DOACs can be safely used in patients with forms of VHD such as aortic stenosis, aortic regurgitation and mitral regurgitation. 51,52 DOACs may therefore prove to be as effective as warfarin in patients with VHD, which will positively impact RHD care in SSA. Consequently, the efficacy of rivaroxaban is being compared to warfarin in patients with RHD and AF at high risk of stroke in the INVICTUS trial, an international, multicentre, randomized open-label trial that has enrolled >25% of its participants (1150) from 14 SSA countries 53 (Table 1).…”