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Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation.

ABSTRACT: Importance:Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk. Objective:To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture. Design, Setting, and Participants:This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA2DS2-VASc (congestive heart failure, hypertension, age [>65 years?=?1 point; >75 years?=?2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The final analysis included 167?275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019. Exposures:Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban). Main Outcomes and Measures:Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results:In the study population of 167?275 patients with AF (38.0% women and 62.0% men; mean [SD] age, 68.9 [12.5] years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 [95% CI, 0.45-0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47-0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75-0.98]). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis. Conclusions and Relevance:In this real-world population of 167?275 patients with AF, use of DOACs-particularly apixaban-compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture.

SUBMITTER: Lutsey PL

PROVIDER: S-EPMC6902159 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation.

Lutsey Pamela L PL Norby Faye L FL Ensrud Kristine E KE MacLehose Richard F RF Diem Susan J SJ Chen Lin Y LY Alonso Alvaro A

JAMA internal medicine 20200201 2

<h4>Importance</h4>Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk.<h4>Objective</h4>To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with ...[more]

PMID: 31764956

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Project description:ObjectiveOur study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin.MethodsWe searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893).ResultsWe included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81-1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82-1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80-0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76-0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin.ConclusionThe meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.

Project description:It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed. We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585). Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.

Project description:BackgroundThis study aimed to investigate the prevalence and factors associated with the initiation of oral anticoagulation among patients with acute ischemic stroke (AIS) and concurrent atrial fibrillation (AF) at discharge in China.MethodsWe continuously included hospitalized patients with AIS with an AF diagnosis registered in the computer-based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation (CASE II) from January 2016 to December 2020 and divided them into a and non-anticoagulant groups according to the medications at discharge. Binary logistic regression was used to determine the factors associated with the prescription of anticoagulants in patients with AF.ResultsA total of 16,162 patients were enrolled. The mean age was 77 ± 9 years, 8,596 (53.2%) were males, and the median baseline National Institute of Health Stroke Scale score was 5 (2-12). Of the 14,838 patients without contraindications of antithrombotic therapy, 6,335 (42.7%) patients were initiated with anticoagulation treatment at discharge. Prior history of hemorrhagic stroke (OR 0.647, p < 0.001) and gastrointestinal bleeding (OR 0.607, p = 0.003) were associated with a lower rate of anticoagulation at discharge. Patients with any intracranial hemorrhage (OR 0.268, p < 0.001), gastrointestinal bleeding (OR 0.353, p < 0.001), or pneumonia during hospitalization (OR 0.601, p < 0.001) were less likely to receive anticoagulants at discharge. Among 7,807 patients with previously diagnosed AF and high risk of stroke (CHA2DS2-VASc ≥2), only 1,585 (20.3%) had been receiving anticoagulation treatment prior to the onset of stroke. However, the mean international normalized ratio (INR) was 1.5 on the first test during hospitalization in patients receiving warfarin. Patients complicated with a previous history of ischemic stroke/transient ischemic attack (TIA; OR 2.303, p < 0.001) and peripheral artery disease (OR 1.456, p = 0.003) were more common to start anticoagulants.ConclusionsLess than half of patients with AIS and concurrent AF initiated guideline-recommended oral anticoagulation at discharge, while only 20% of patients with previously diagnosed AF with a high risk of stroke had been using anticoagulants prior to the onset of stroke, which highlights a large care gap in hospitalized stroke patients and the importance of AF management.

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Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation.

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Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation.

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