November 4, 2020Annals of PharmacotherapyOpen Access

Off-label Use for Direct Oral Anticoagulants: Valvular Atrial Fibrillation, Heart Failure, Left Ventricular Thrombus, Superficial Vein Thrombosis, Pulmonary Hypertension—a Systematic Review

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Why the study?

To evaluate clinical literature evaluating direct oral anticoagulant therapy for non-Food and Drug Administration approved indications.

Are direct oral anticoagulants (DOACs) safe and effective for off-label indications including AF with VHD, HF, LVT, SVT, and PH?

Structured PICO

Are direct oral anticoagulants (DOACs) safe and effective for off-label indications including AF with VHD, HF, LVT, SVT, and PH?

Population

Patients with atrial fibrillation (AF) with valvular heart disease (VHD), heart failure (HF), left ventricular thrombus (LVT), superficial vein thrombosis (SVT), or pulmonary hypertension (PH)

Intervention

Direct oral anticoagulants (DOACs)

Comparator

Standard therapy (e.g., warfarin, fondaparinux) depending on the indication

Outcome

Safety and efficacy of DOACs for off-label indications

DOACs can be considered for AF with VHD (excluding mitral stenosis or mechanical valves) and as an alternative for SVT and CTEPH, but further studies are needed for HF and LVT.

Implication

May support considering DOACs for AF with most VHD and as SVT alternative; leaves open roles in HF and LVT.

Abstract

OBJECTIVE: To evaluate clinical literature for direct oral anticoagulants (DOACs) therapy for non-Food and Drug Administration approved indications. DATA SOURCES: Articles from MEDLINE, Cochrane Library, Google Scholar, and OVID databases were reviewed from 1946 through September 4, 2020. STUDY SELECTION AND DATA EXTRACTION: Fully published studies assessing DOACs for atrial fibrillation (AF) with valvular heart disease (VHD), heart failure (HF), left ventricular thrombus (LVT), superficial vein thrombosis (SVT), or pulmonary hypertension (PH) were evaluated. DATA SYNTHESIS: Our review showed that DOACs are safe to use in patients with AF and VHD except for mitral stenosis or mechanical heart valve. Rivaroxaban 2.5 mg twice daily should be used with caution in patients with HF with reduced ejection fraction until further evaluation is performed. Four retrospective studies for DOAC use in patients with LVT showed conflicting results. One phase 3 randomized controlled trial showed noninferiority of rivaroxaban to fondaparinux for SVT treatment. The use of DOACs for pulmonary arterial hypertension was not evaluated in any clinical study, but 2 retrospective studies for the use of DOACs in patients with chronic thromboembolic PH (CTEPH) showed similar efficacy between DOACs and warfarin. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review provides clinicians with a comprehensive literature review surrounding DOAC use in common off-label indications. CONCLUSION: DOACs can be considered for AF complicated by VHD except for mitral stenosis or mechanical valve replacement. DOACs (especially rivaroxaban) are considered as an alternative therapy for SVT and CTEPH. Further prospective studies for DOAC uses are needed for HF or LVT.