Fracture risks in patients with atrial fibrillation treated with different oral anticoagulants: a meta-analysis and systematic review.
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ABSTRACT: Aims
evidence on the difference in fracture risks for patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs) versus warfarin remains controversial. We aim to compare the fracture risks between the DOAC and warfarin prescriptions among the AF patients.Methods and results
we systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science up to 19 April 2021 for relevant studies. And the observational studies regarding the relationship between the DAOC versus warfarin prescriptions and fracture risks among the patients with AF were included in this meta-analysis. Two investigators independently screened the articles and extracted the relevant data. A random- or fixed-effect model was applied to calculate the pooled hazard ratio/relative ratios with 95% confidence intervals of fracture risks associated with the DOAC and warfarin prescriptions. Six studies comprising 351,208 patients and 9,424 fractures were included in this meta-analysis. Overall, the AF patients treated with DOACs tend to present a lower risk of any fracture compared with those treated with warfarin (relative ratio: 0.82, 95% confidence interval (CI): 0.74-0.91). Sub-analyses for each individual DOAC indicate that apixaban and rivaroxan are associated with lower risk of any fracture compared with warfarin (HR: 0.75, 95% CI: 0.60-0.92, and HR: 0.79, 95% CI: 0.71-0.88, respectively).Conclusion
this meta-analysis suggests that DOAC users have a lower risk of fractures than the warfarin users. The results of this study may provide optimal anticoagulation opportunities for AF patients with high fracture risk factors.
SUBMITTER: Xie X
PROVIDER: S-EPMC8789302 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Evidence on the differences in fracture risk associated with non-vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta-analysis to assess the fracture risk associated with NOACs and warfarin. Methods and Results We searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random-effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77-0.91; P<0.001) with low heterogeneity (I2=38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81-0.98; P=0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54-1.01; P=0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were quite consistent, indicating the robustness of our findings. Conclusions Compared with warfarin, NOACs are associated with lower risks of bone fracture.
| S-EPMC8174313 | biostudies-literature
Project description:Aim To determine to what extent active cancer influences the benefit-risk relationship among patients with atrial fibrillation receiving oral anticoagulants for stroke prevention. Methods In this cohort study of all patients with atrial fibrillation in the Swedish Patient register during 2006 to 2017, 8,228 patients with active cancer and 323,394 without cancer were followed up to 1 year after initiation of oral anticoagulants. Cox regression models, adjusting for confounders and the competing risk of death, were used to assess risk of cerebrovascular and bleeding events. Results Among patients treated with oral anticoagulants, the risk for cerebrovascular events did not differ between cancer patients and noncancer patients (subhazard ratio [sHR]: 1.12, 95% confidence interval [CI]: 0.98-1.29). Cancer patients had a higher risk for bleedings (sHR: 1.69, CI: 1.56-1.82), but not for fatal bleedings (sHR: 1.17, CI: 0.80-1.70). Use of nonvitamin K oral anticoagulants was associated with lower risk of both cerebrovascular events and bleedings compared with warfarin. Conclusion Patients with atrial fibrillation and active cancer appear to have similar net cerebrovascular benefit of oral anticoagulant treatment to patients without cancer, despite an increased risk of nonfatal bleedings. Use of nonvitamin K oral anticoagulants was associated with lower risk of all studied outcomes.
| S-EPMC8169314 | biostudies-literature
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
Project description:OBJECTIVE: An underuse of oral anticoagulants (OAC) in patients with atrial fibrillation (AF) has been suggested, as only 50% of all patients with AF receive OAC treatment. Whether this is due to contraindications, lack of an indication to treat, or an expression of underuse is sparsely investigated. This study therefore aimed to characterize individuals without OAC treatment in a real-life population of patients with AF. DESIGN: Retrospective cross-sectional study. The medical records were scrutinized in order to identify the type of AF, risk factors for embolism and bleeding, and other factors of importance for OAC treatment. SETTING: The municipalities of Skellefteå and Norsjö, northern Sweden. SUBJECTS: A total of 2274 living residents with at least one verified episode of AF on or before December 31, 2010. MAIN OUTCOME MEASURES: Prevalence of treatment with OAC and documented reasons to withhold OAC treatment. RESULTS: Among all 2274 patients with AF, 1187 (52%) were not treated with OAC. Of the untreated patients, 19% had no indication or had declined or had experienced adverse effects other than bleeding on warfarin treatment. The most common reason to withhold OAC was presence of risk factors for bleeding, found in 38% of all untreated patients. Furthermore, a documented reason could be identified to withhold OAC in 75%. CONCLUSIONS: Among patients with AF without OAC treatment a reason could be identified to withhold OAC in 75%. The underuse of OAC is estimated to be 25%.
| S-EPMC4278389 | biostudies-literature
Project description:Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design Systematic review, network meta-analysis, and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results 23 randomised trials involving 94?656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.Conclusions The network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registration PROSPERO CRD 42013005324.
| S-EPMC5704695 | biostudies-other
Project description:BackgroundDirect-acting oral anticoagulants (DOACs) have demonstrated superior efficacy in preventing stroke and death compared with warfarin in patients with atrial fibrillation (AF), but their influence on dementia risk remains unclear.ObjectivesThe purpose of this study was to evaluate the relative risks of dementia in DOAC vs warfarin in patients with AF.MethodsAn electronic literature search was conducted to retrieve studies reporting comparisons of dementia incidence between patients treated with DOACs and warfarin for AF. HRs and 95% CI were pooled in a random-effects meta-analysis. Meta-regression was performed to identify prognostic baseline variables. Network meta-analysis was performed to determine dementia risk between individual DOACs and warfarin.ResultsTen studies (n = 342,624) were retrieved. DOAC was associated with a significantly lower risk of developing dementia compared with warfarin (HR: 0.88; 95% CI: 0.80-0.98; P = 0.017; I2 = 75%); significance was also seen in Asian patients (HR: 0.81; 95% CI: 0.68-0.86) but not non-Asian patients. Subgroup analyses of propensity score-matched studies and patients aged 65-75 years showed similar significance, but not for patients aged ≥75 years. Meta-regression found that a lower mean age corresponded to significantly greater favoring of DOAC over warfarin. Network meta-analysis found significant reductions in dementia risk over warfarin for rivaroxaban (HR: 0.854; 95% CI: 0.763-0.955), apixaban (HR: 0.881; 95% CI: 0.778-0.997), and dabigatran (HR: 0.871; 95% CI: 0.770-0.987); the highest-ranked treatment based on P scores was edoxaban.ConclusionsThe use of DOAC in AF significantly reduces dementia risk compared with warfarin, particularly in Asian patients. The possible reversal of this effect with increasing age merits further randomized trials with long-term follow-up. (Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: A Systematic Review and Meta-Analysis; CRD42022365634).
| S-EPMC10715893 | biostudies-literature
Project description:The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.
| S-EPMC6490750 | biostudies-literature
Project description:Background Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking. Objectives This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N = 32,275) data. Methods Patients were classified into high-risk (age: ≥80 years; CHADS2 score: ≥2; and presence of ≥1 bleeding risk factor: creatinine clearance of 15-30 mL/minute, prior bleeding at critical sites, body weight of ≤45 kg, or continuous antiplatelet use) and reference groups. Results In the high-risk (n = 7,104) and reference (n = 25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95% CI: 0.36-0.79) and all-cause death (HR: 0.65; 95% CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95% CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding. Conclusions High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006) Central Illustration
| S-EPMC9700004 | biostudies-literature
Project description:The coexistence of coronary artery disease and atrial fibrillation (AF) in the same individuals raises great concern about the co-treatment with different antithrombotic agents in the case of percutaneous coronary interventions (PCI). The advent of direct oral anticoagulants (DOACs) revolutionised the therapy of AF; less is known, however, about the safety and efficacy of therapy with DOACs in combination with antiplatelet agents after PCI. We performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for any bleeding (AB), cardiovascular events (CVE), major bleeding (MB), myocardial infarction (MI), and stent thrombosis (ST) at follow-up: 4849 patients have been included in the analysis. When compared with patients receiving standard triple therapy (vitamin-K antagonists plus double antiplatelet therapy [VKAs plus DAPT]), patients receiving DOACs (rivaroxaban/dabigatran plus either one or two antiplatelet agents) had a statistically significant lower risk of AB (RR, 0.66; 95% CI, 0.59-0.75, p<0.00001), as well as of MB (RR, 0.59; 95% CI, 0.47-0.73, p<0.00001). Equivalent efficacy was found about CVE (RR, 1.03; 95% CI, 0.89-1.19, p=0.69), MI (RR, 1.09; 95% CI, 0.81-1.45, p=0.57), while slight although non-statistically significant increased risk of ST was found (RR, 1.46; 95% CI, 0.86-2.48, p=0.16). In conclusion, DOACs are safer than and as effective as warfarin when used in patients with AF undergoing PCI; dual therapy with DOACs is comparable to triple therapy in terms of safety and efficacy.
| S-EPMC6045730 | biostudies-other
Project description:BackgroundRandomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs.ObjectivesThe authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes.MethodsMedical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively.ResultsAt the cutoff values of eGFR of <15, 15-50, and >50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin.ConclusionsThe adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages.
| S-EPMC9627870 | biostudies-literature