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Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.

ABSTRACT: BACKGROUND:We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk. METHODS:We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age?>?=65?years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose. RESULTS:We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3?months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR?=?1.44; 95% CI 1.14-1.8, P?=?0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P?=?0.002) and gastrointestinal bleeding (Dabigatran: HR?=?1.48; 95% CI 1.08-2, P?=?0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR?=?0.59; 95% CI 0.43-0.8, P?

SUBMITTER: Briasoulis A

PROVIDER: S-EPMC6998084 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.

Briasoulis Alexandros A Gao Yubo Y Inampudi Chakradhari C Alvarez Paulino P Asleh Rabea R Chrischilles Elizabeth E Leira Enrique C EC Vaughan-Sarrazin Mary M

BMC cardiovascular disorders 20200203 1

<h4>Background</h4>We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk.<h4>Methods</h4>We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age > =65 years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received ...[more]

PMID: 32013886

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Project description:ImportanceThe CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata.ObjectiveTo evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group.Design, setting, and participantsThis cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019.ExposureInitiation of oral anticoagulants.Main outcomes and measuresWe observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes.ResultsWe identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends.Conclusions and relevanceThe observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Project description:Background: The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This study aims at estimating the prevalence of DOAC off-label doses in AF patients. Methods: Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses. Results: A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19-28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16-24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban; P interaction =0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3-7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4-6%). Conclusion: This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.

Project description:Background Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long-term adherence to DOACs and clinical outcomes in real-world clinical practice is not well understood. This study evaluated long-term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system. Methods and Results We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long-term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group-based trajectory models. Factors associated with long-term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long-term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA2DS2-VASc (0-1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05-1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30-0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence. Conclusions Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.

Dataset Information

Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.

Publications

Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.

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