Classification and characteristics of on‐label and off‐label apixaban use in Denmark and Sweden

Abstract

Purpose: To estimate the proportion of apixaban users who received the drug for on-label indications and characterise the patients using apixaban for on-label and off-label indications. Methods:We report results from two independently conducted studies in Denmark and Sweden,with 19,709 Danish and 17,592 Swedish patients, who received at least one outpatient dispensing of apixaban as identified through nationwide prescription registries. Indications, inferred from inpatient and hospital diagnoses recorded at the initial apixaban dispensing, were classified as on-label, off-label, or unclassified according to the Summary of Product Characteristics. All diagnoses were retrieved using inpatient or outpatient hospital diagnoses at the first outpatient dispensing during the study period. Results: Men comprised 52% of the users in both Denmark and Sweden. The median age was 76 years (interquartile range [IQR]: 68-83 years) among Danish patients and 74 years (IQR: 67-82 years) among Swedish patients. An on-label indication could be assigned to 82.6% (95% confidence interval [CI]: 82.1%-83.1%) of the Danish patients and 86.4% (95% CI: 85.9%-86.9%) of the Swedish patients. The main on-label indication for apixaban was non-valvular atrial fibrillation (NVAF), which accounted for 76.1% of the indications in Denmark and 69.1% of the indications in Sweden. Off-label indications were assigned to 10.8% (95% CI: 10.3-11.2) of the Danish patients (main indication possible mechanical heart valve) and 7.7% (95% CI: 7.3-8.1) of the Swedish patients (main indication off-label atrial fibrillation). Conclusion: The majority of apixaban initiators in Denmark and Sweden received apixaban for an on-label indication, primarily for NVAF.

Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi

“…Oral factor Xa and direct thrombin inhibitors have been approved for use and are associated with a reduction in the risk of stroke or systemic embolism (SSE) in patients with nonvalvular atrial fibrillation (AF) and venous thromboembolism. [5][6][7][8][9][10][11] Clinical use of these direct oral anticoagulants (DOACs) has been extended to off-label indications such as heparin-induced thrombocytopenia and antiphospholipid syndrome [12][13][14] ; however, the assumption of generalized interchangeability between DOACs and warfarin is potentially problematic. For example, dabigatran etexilate used for thromboprophylaxis of mechanical heart valves demonstrated higher rates of both ischemic stroke and bleeding.…”

Low-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

“…Underdosing is more common than overdosing in real-world studies. The prevalence of underdosing in real-world studies ranges from 8% to 52% [ 38 ]. Underdosing of NOACs more commonly occurs in studies of Asian patients (20–50%) than in studies of non-Asian patients (8–20%).…”

Direct-Acting Oral Anticoagulants: A Resident-Based Workshop to Improve Knowledge and Confidence

“… 2 – 4 Multiple studies have shown that DOACs are frequently used off-label and at incorrect doses. 5 , 6 Such practice places patients at risk for bleeding and thromboembolic events. 7 , 8 Inappropriate prescribing is likely a consequence of inadequate DOAC education, familiarity, and prescribing experience.…”