Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation

Lau, Wallis C.Y.; Cheung, Ching Lung; Man, Kenneth K C; Chan, Esther W.; Sing, Chor‐Wing; Lip, Gregory Y. H.; Siu, Chung Wah; Lam, Joanne K.Y.; Lee, Alan C.H.; Wong, Ian Chi Kei

doi:10.7326/m19-3671

Cited by 56 publications

(57 citation statements)

References 51 publications

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“…Preclinical studies have shown that several vitamin K-dependent proteins, such as matrix Gla protein and osteopontin, play a role in bone metabolism [9], and this has led to concerns that warfarin may increase the risk for osteoporotic fracture. These results correlate with clinical findings that propose a connection between warfarin and an increased risk of osteoporotic fractures [8][9][10][11][14][15][16][17]. Furthermore, patients who are treated with VKAs are subjected to several dietary restrictions that may contribute to a low bone mineral density.…”

Section: Introductionsupporting

confidence: 83%

“…Values are presented as mean ± standard deviation or n (%) AAD anti-arrhythmic drug, ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin II receptor blocker, ASD absolute standardized difference, COPD chronic obstructive pulmonary disease, DHP dihydropyridine, IPTW inverse probability of treatment weighting recent studies [14][15][16][17]. In the present study, we extended prior observations by enrolling a larger number of participants and allowing a longer follow-up.…”

Section: Table 1 (Continued)mentioning

confidence: 85%

“…And we used propensity score-weighting for multiple treatment options, accounting for the differences in baseline characteristics of all the four anticoagulants (warfarin and 3 NOACs) simultaneously. This approach makes it possible to generalize the results to the entire population who would be eligible to receive any of the four anticoagulants, which may better reflect real-world clinical practice [17]. Prior studies have reported that warfarin therapy might interfere the process of bone formation.…”

Section: Table 1 (Continued)mentioning

confidence: 99%

“…Evidence is scarce regarding possible differences in the fracture risk by individual NOACs [15,17]. Prior studies analyzing administrative claim data of Hong Kong and Taiwan reported there were no significant differences in fracture risk in head-to-head comparisons between NOACs, although the strongest beneficial effect estimates were observed for apixaban when comparing individual NOACs with warfarin [15,17].…”

Section: Table 1 (Continued)mentioning

confidence: 99%

“…The NOACs are also associated with a lower potential risk for drug-drug interactions than warfarin [13]. However, data on osteoporotic fracture risks with NOAC use are more limited [14][15][16][17], and it remains unclear which anticoagulant type or NOAC agent should be recommended as the first choice for a patient who is also at risk for osteoporotic fracture.…”

Section: Introductionmentioning

confidence: 99%

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Risk for osteoporotic fractures in patients with atrial fibrillation using different oral anticoagulants

et al. 2021

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Background We aimed to investigate the comparative risk of fracture among patients with atrial fibrillation (AF) treated with warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). Methods Using the Korean National Health Insurance Service database, patients with AF who received a prescription for apixaban, dabigatran, rivaroxaban, or warfarin between 2013 and 2016 were included. Risk of major fractures (osteoporotic hip, vertebral, or pelvic fractures) were compared using inverse probability of treatment weighting. Results There were 70,481 patients identified (41.3% women; mean [SD] age 70.5 [11.3] years); 16,992 apixaban, 22,514 dabigatran, 27,998 rivaroxaban, and 29,390 warfarin users. During a median follow-up of 390 days, 2412 major fractures occurred with weighted incidences per 100 patient-years of 2.56 for apixaban, 2.39 for dabigatran, 2.78 for rivaroxaban, and 3.43 for warfarin. NOAC use was associated with a lower risk for fracture than warfarin use: HR 0.70 (95% confidence interval [CI] 0.57–0.86) for apixaban, HR 0.69 (95% CI 0.60–0.78) for dabigatran, and HR 0.79 (95% CI 0.70–0.90) for rivaroxaban. In head-to-head comparisons between NOACs, there was no significant difference between apixaban and dabigatran. Rivaroxaban was associated with a higher risk for fracture than dabigatran (HR 1.15, 95% CI 1.02–1.31). Conclusion In patients with AF, NOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of NOAC type, except for rivaroxaban. These associations may help inform benefit–risk assessments when choosing between the different anticoagulant types.

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Section: Introductionsupporting

confidence: 83%

Section: Table 1 (Continued)mentioning

confidence: 85%

Section: Table 1 (Continued)mentioning

confidence: 99%

Section: Table 1 (Continued)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Risk for osteoporotic fractures in patients with atrial fibrillation using different oral anticoagulants

et al. 2021

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Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age

Wang¹,

Chan

Coghill

et al. 2021

JAMA Intern Med

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The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear.OBJECTIVE To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems. DESIGN, SETTING, AND PARTICIPANTSThis population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication.EXPOSURES Prenatal antipsychotic exposure. MAIN OUTCOMES AND MEASURESPreterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. RESULTSThe cohorts included 333 749 mother-child pairs for ADHD (mean [SD] maternal age at delivery, 31.46 [5.03] years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean [SD] maternal age at delivery, 31.56 [5.01] years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% CI, 0.83-1.61) for ADHD and 1.06 (95% CI, 0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95% CI, 1.13-1.75) for preterm birth and 1.36 (95% CI, 0.86-2.14) for small for gestational age when comparing gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure

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Gastrointestinal bleeding risk with rivaroxaban vs aspirin in atrial fibrillation: A multinational study

Fanning

Wong

et al. 2020

Pharmacoepidemiology and Drug

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Purpose: Comparative gastrointestinal bleeding (GIB) risk between rivaroxaban and low-dose aspirin is unknown in patients with atrial fibrillation (AF). This study investigated GIB risk with rivaroxaban vs aspirin among two separate AF cohorts in Hong Kong and the United Kingdom, using a common protocol approach. Methods: This was a population-based cohort study using separate data from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (2010-2018) and The Health Improvement Network (THIN) database in the United Kingdom (2011-2017). Patients with AF newly prescribed aspirin or rivaroxaban were included. Cox proportional hazards regression was used to compare GIB risks for rivaroxaban vs aspirin, accounting for confounders using propensity score fine stratification approach. Results: In CDARS, 29 213 patients were included; n = 1052 (rivaroxaban), n = 28 161 (aspirin). Crude GIB event rates per 100 patient-years in CDARS were 3.0 (aspirin) and 2.6 (rivaroxaban). No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.04, 95%CI = 0.76-1.42), and in dose-stratified analyses (HR = 1.21, 95%CI = 0.84-1.74 [20 mg/day]; HR = 0.80, 95%CI = 0.44-1.45 [≤15 mg/day]). In THIN, 11 549 patients were included,

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Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation

Cited by 56 publications

References 51 publications

Risk for osteoporotic fractures in patients with atrial fibrillation using different oral anticoagulants

Risk for osteoporotic fractures in patients with atrial fibrillation using different oral anticoagulants

Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age

Gastrointestinal bleeding risk with rivaroxaban vs aspirin in atrial fibrillation: A multinational study

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