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Association of Direct Oral Anticoagulants vs. Vitamin K Antagonists With Fractures in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Current evidence regarding the application of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) on the fracture risk is inconsistent. Therefore, we conducted a meta-analysis to evaluate the fracture risk of DOACs vs. VKAs in patients with atrial fibrillation (AF). Methods: The PubMed and Embase databases were systematically searched until June 2021 for all the studies that reported oral anticoagulants in AF patients. The random-effect model with an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). Results: A total of 10 studies were included in this meta-analysis. Among AF patients receiving anticoagulants, DOAC users showed a reduced risk of any fracture compared to those with VKAs (RR = 0.80; 95% CI: 0.70-0.91) regardless of gender [males (RR = 0.79; 95% CI: 0.67-0.92) and females (RR = 0.71; 95% CI: 0.57-0.89)]. Apixaban (RR = 0.75; 95% CI: 0.60-0.92) and rivaroxaban (RR = 0.73; 95% CI: 0.61-0.88), but not dabigatran and edoxaban, were associated with a decreased risk of any fracture compared with VKAs. DOAC users had decreased risks of osteoporotic fractures (RR = 0.63; 95% CI: 0.47-0.84) and hip/pelvic fractures (RR = 0.88; 95% CI: 0.79-0.97) compared to those treated with VKAs. Conclusions: Our meta-analysis suggested that the use of DOACs was associated with a reduced risk of any fracture compared with VKAs. Further studies should confirm our findings.

SUBMITTER: Wu X

PROVIDER: S-EPMC8339256 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Risk of fracture in patients with non-valvular atrial fibrillation initiating direct oral anticoagulants vs. vitamin K antagonists.

Project description:AimsTo determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use.Methods and resultsUsing Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46-0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31-0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79-1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls.ConclusionProlonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF.

| S-EPMC8453296 | biostudies-literature

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis.

Project description:BackgroundDirect oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established.ObjectiveWe performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF.MethodsAn online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users.ResultsThe use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52-0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74-0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52-0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50-0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47-0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78-1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78-1.06; p 0.24).ConclusionsIn comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

| S-EPMC7886836 | biostudies-literature

Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation.

Project description:Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for more than 50 years. VKAs are mainly used for the prevention of stroke in patients with atrial fibrillation (AF) and the treatment and secondary prevention of venous thromboembolism. In the past 5 years, four new agents-the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or non-VKA oral anticoagulants]-have been approved for these and other indications. Despite these new treatment options, the VKA warfarin currently remains the most frequently prescribed oral anticoagulant. The availability of DOACs provides an alternative management option for patients with AF, especially when the treating physician is hesitant to prescribe a VKA owing to associated limitations, such as food and drug interactions, and concerns about bleeding complications. Currently available real-world evidence shows that DOACs have similar or improved effectiveness and safety outcomes compared with warfarin. Treatment decisions on which DOAC is best suited for which patient to maximize safety and effectiveness should take into account not only clinically relevant patient characteristics but also patient preference. This article reviews and highlights real and perceived implications of VKAs for the prevention of stroke in patients with non-valvular AF, with specific reference to their strengths and weaknesses compared with DOACs.

| S-EPMC5337242 | biostudies-literature

Geriatric Conditions and Prescription of Vitamin K Antagonists vs. Direct Oral Anticoagulants Among Older Patients With Atrial Fibrillation: SAGE-AF.

Project description:Background: Geriatric conditions are common among patients with atrial fibrillation (AF) and relate to complications of oral anticoagulation (OAC). Objective: To examine the prevalence of geriatric conditions among older patients with AF on OAC and relate type of OAC to geriatric conditions. Methods: Participants had a diagnosis of AF, were aged ?65 years, CHA2DS2VASC ? 2, and had no OAC contraindications. Participants completed a 6-component geriatric assessment that included validated measures of frailty (CHS Frailty Scale), cognitive function (MoCA), social support (MOS), depressive symptoms (PHQ9), vision, and hearing. Type of OAC prescribed was documented in medical records. Results: 86% of participants were prescribed an OAC. These participants were on average aged 75.7 (SD: 7.1) years, 49% were women, two thirds were frail or pre-frail, and 44% received a DOAC. DOAC users were younger, had lower CHA2DS2VASC and HAS-BLED scores, and were less likely to be frail. In Massachusetts, pre-frailty was associated with a significantly lower odds of DOAC vs. VKA use (OR = 0.64, 95%CI 0.45, 0.91). Pre-frailty (OR = 0.33, 95%CI 0.18-0.59) and social isolation (OR = 0.38, 95%CI 0.14-0.99) were associated with lower odds of DOAC receipt in patients aged 75 years or older. Social isolation was associated with higher odds of DOAC use (OR = 2.13, 95%CI 1.05-4.29) in patients aged 65-74 years. Conclusions: Geriatric conditions were common and related to type of OAC prescribed, differentially by age group. Research is needed to evaluate whether a geriatric examination can be used clinically to better inform OAC decision-making in older patients with AF.

| S-EPMC6831524 | biostudies-literature

Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation.

Project description:ObjectiveWe compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.MethodsWe conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).ResultsWe included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09).InterpretationDOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.

| S-EPMC6563449 | biostudies-literature

A Network Meta-Analysis Comparing Osteoporotic Fracture among Different Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation.

Project description:BackgroundThere are limited studies comparing the risk of osteoporosis and fractures between different direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA) in non-valvular atrial fibrillation (AF). Using a network meta-analysis (NMA), we compared osteoporotic fractures among 5 different treatment arms, viz. dabigatran, rivaroxaban, apixaban, edoxaban, and VKA.MethodsTen studies, including 5 randomized control trials and 5 population-based studies, with a total of 321,844 patients (148,751 and 173,093 in the VKA and DOAC group, respectively) with a median follow-up of 2 years, were included. A Bayesian random-effects NMA model comparing fractures among the treatment arms was performed using MetInsight V3. Sensitivity analysis excluded studies with the highest residual deviances from the NMA model.ResultsThe mean age of the patients was 70 years. The meta-analysis favored DOACs over VKA with significantly lower osteoporotic fracture (odds ratio [OR], 0.77; 95% credible interval [CrI], 0.70-0.86). The NMA demonstrated that fractures were significantly lower with apixaban compared with dabigatran (OR, 0.64; 95% CrI, 0.44-0.95); however, fractures were statistically similar between apixaban and rivaroxaban (OR, 0.84; 95% CrI, 0.58-1.24) and dabigatran and rivaroxaban (OR, 1.32; 95% CrI, 0.90-1.87). Based on the Bayesian model of NMA, the probability of osteoporotic fracture was highest with VKA and lowest with apixaban, followed by rivaroxaban, edoxaban, and dabigatran.ConclusionsThe decision to prescribe anticoagulants in elderly patients with AF should be made not only based on thrombotic and bleeding risks but also on the risk of osteoporotic fracture; these factors should be considered and incorporated in contemporary cardiology practice.

| S-EPMC8206613 | biostudies-literature

Non-valvular Atrial Fibrillation in CKD: Role of Vitamin K Antagonists and Direct Oral Anticoagulants. A Narrative Review.

Project description:Atrial fibrillation (AF) is the most common arrhythmia in chronic kidney disease (CKD), with a close bidirectional relationship between the two entities. The presence of CKD in AF increases the risk of thromboembolic events, mortality and bleeding. Vitamin K antagonists (VKA) have been the mainstay of treatment for the prevention of thromboembolic events in AF until recently, with confirmed benefits in AF patients with stage 3 CKD. However, the risk-benefit profile of VKA in patients with AF and stages 4-5 CKD is controversial due to the lack of evidence from randomized controlled trials. Treatment with VKA in CKD patients has been associated with conditions such as poorer anticoagulation quality, increased risk of bleeding, faster progression of vascular/valvular calcification and higher risk of calciphylaxis. Direct oral anticoagulants (DOACs) have shown equal or greater efficacy in stroke/systemic embolism prevention, and a better safety profile than VKA in post-hoc analysis of the pivotal randomized controlled trials in patients with non-valvular AF and stage 3 CKD, yet evidence of its risk-benefit profile in more advanced stages of CKD is scarce. Observational studies associate DOACs with a good safety/effectiveness profile compared to VKA in non-dialysis CKD patients. Further, DOACs have been associated with a lower risk of acute kidney injury and CKD development/progression than VKA. This narrative review summarizes the evidence of the efficacy and safety of warfarin and DOACs in patients with AF at different CKD stages, as well as their effects on renal function, vascular/valvular calcification and bone health.

| S-EPMC8484537 | biostudies-literature

Perioperative interruption of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: A comparative analysis.

Project description:BackgroundThere is a paucity of studies comparing postoperative thromboembolic and major bleeding complications following perioperative interruption of the direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs).Objective/methodsWe conducted a retrospective cohort study to compare postoperative thromboembolic and major bleeding outcomes following perioperative interruption of DOACs and VKAs in patients with atrial fibrillation. The primary efficacy and safety outcomes were the 30-day postoperative rates of arterial thromboembolic events (ATEs) and major bleeding, respectively. The secondary outcomes included the 30-day rates of clinically relevant nonmajor bleeding (CRNMB) and overall mortality. Thromboembolic, major bleeding, and mortality outcomes were independently adjudicated. Multivariable mixed-effects logistic-regression models were used to adjust for potential confounding variables between the DOAC and VKA cohorts.ResultsA total of 325 DOAC patients undergoing 351 procedures and 199 VKA patients undergoing 221 procedures were included. The 30-day ATE rate was 0.57% (95% confidence interval [CI], 0.27-0.8) in the DOAC cohort. There were no ATEs in the VKA cohort. The 30-day rates of major bleeding were 0.57% (95% CI, 0.27-0.8) and 3.62% (95% CI, 0-7.3) in the DOAC and the VKA cohorts, respectively. There were significantly more postoperative major bleeding events in the VKA cohort. The 30-day rate of CRNMB was 4.27% (95% CI, 4.15-4.42) in the DOAC cohort and 4.52% (95% CI, 3.67-5.38) in the VKA cohort. There were 2 deaths in the VKA cohort, one of which was deemed to be a fatal nonsurgical bleeding event.ConclusionsThe perioperative interruption of VKAs may be associated with higher postoperative major bleeding rates as compared to DOACs. Careful postoperative reinitiation and monitoring of VKA anticoagulation may be warranted following surgical procedures.

| S-EPMC6971332 | biostudies-literature

Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists: A systematic review and meta-analysis.

Project description:A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)-experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real-life VKA-experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English-language studies indexed any time before October 2018. We included studies of VKA-experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta-analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA-experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95% CI 1.19-2.19, I2 = 65%] and 1.29 [95% CI 1.10-1.52, I2 = 0%], respectively), but not for rivaroxaban. The use of dabigatran in VKA-experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95% CI 1.36-1.94, I2 = 30%]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95% CI 0.32-0.64, I2 = 0%]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real-life VKA-experienced oral anticoagulant users may be confounded by the reason for switching.

| S-EPMC6973083 | biostudies-literature

New oral anticoagulants vs vitamin K antagonists: benefits for health-related quality of life in patients with atrial fibrillation.

Project description:New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL.

| S-EPMC4025166 | biostudies-literature

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