Risk of osteoporosis in patients treated with direct oral anticoagulants vs. warfarin: an analysis of observational studies
Ontology highlight
ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC10570517 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundIn patients with atrial fibrillation (AF) treated with direct oral anticoagulants (DOAC), bleeding risk scores provide only modest discrimination for major or intracranial bleeding. However, warfarin experience may impact HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly) score performance in patients evaluated for DOACs, as HAS-BLED was derived and validated in warfarin cohorts.MethodsWe performed a retrospective cohort study of patients prescribed DOAC for AF in the Veterans Health Administration between 2010 and 2017. We determined modified HAS-BLED score discrimination and calibration for bleeding, for patients treated with DOAC, stratified by prior warfarin exposure. We also determined the association between DOAC-warfarin-naïve status to bleeding (nonintracranial and intracranial) with DOAC-warfarin-experienced patients as reference.ResultsThe DOAC analysis cohort included 100, 492 patients with AF (age [mean ± SD]: 72.9 ± 9.6 years; 1.7% female; 90.1% White), of which 26, 760 patients (26.6%) and 73, 732 patients (73.4%) were warfarin experienced or naïve, respectively. HAS-BLED discrimination for bleeds was modest for patients treated with DOAC, regardless of prior warfarin experience (concordance statistics: 0.53-0.59). For DOAC-warfarin-naïve patients, as compared to DOAC-warfarin-experienced patients, adjusted risk of intracranial bleeding was lower, while risk of nonintracranial bleeding was higher (intracranial bleeding propensity adjusted with inverse probability of treatment weights [IPTWs]: hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.78-0.95, p = .0040) (nonintracranial bleeding propensity adjusted with IPTW: HR: 1.15, 95% CI: 1.11-1.19, p < .0001).ConclusionPatients' modified HAS-BLED score at the time of DOAC initiation, regardless of prior warfarin use, provided only modest discrimination for intracranial and nonintracranial bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of modified HAS-BLED score.
| S-EPMC9451662 | biostudies-literature
Project description:Introduction In randomized trials in atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) have a lower risk of bleeding compared with warfarin. However, data from randomized trials may not extrapolate to general population. We aimed to determine the risk of bleeding in patients on DOACs in observational studies. Materials and Methods Observational studies from 1990 to January 2019 were included. A pooled effect hazard ratio (HR) was calculated with a random effects model using the generic inverse variance method. Subgroup analyses according to previous anticoagulants exposure, study type, funding source, and DOAC type (direct thrombin inhibitors vs. factor Xa inhibitors) were conducted. Results A total of 35 studies comprising 2,356,201 patients were included. The average pooled HR for observational data was 0.78 (95% confidence interval [CI] 0.71, 0.85). There were no statistically significant differences in pooled HR by previous exposure to anticoagulants, DOAC type (direct thrombin vs. factor Xa inhibitors), study type, and funding source. Among patients receiving factor Xa inhibitors, patients on apixaban had a lower risk of bleeding compared with warfarin (HR 0.60, 95% CI 0.50, 0.71, p < 0.001) in contrast to those on rivaroxaban (HR 0.98, 95% CI 0.91, 1.06, p = 0.60). Conclusion In observational studies, AF patients on DOACs experience less bleeding events compared with warfarin; however, apixaban and dabigatran, but not rivaroxaban, have a lower risk of bleeding than warfarin.
| S-EPMC7358046 | biostudies-literature
Project description:ImportanceExtending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin.ObjectiveTo compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE.Design, setting, and participantsThis cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023.ExposureDispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE.Main outcomes and measuresThe primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression.ResultsA total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment.Conclusions and relevanceIn this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.
| S-EPMC10427945 | biostudies-literature
Project description:BackgroundObese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of use of direct oral anticoagulants vs use in atrial fibrillation (AF) patients.MethodsUsing data from Quebec provincial administrative databases, for the years2010-2017, we created a retrospective cohort of patients with inpatient or outpatient coding for AF and obesity who were newly prescribed an oral anticoagulant. The primary safety outcome was a composite of intracranial, gastrointestinal, and major bleeding from other sites, and the primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, acute myocardial infarction, and death in the first year after oral anticoagulant initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models.ResultsA total of 2263 patients were included, of whom 1253, 403, and 539 filled a warfarin, standard-dose rivaroxaban, and standard-dose apixaban prescription, respectively. Standard-dose rivaroxaban was associated with a similar composite safety (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.44-1.91) and composite effectiveness risk (HR 1.42; 95% CI 0.99-2.04) compared to warfarin, whereas standard-dose apixaban was associated with a lower composite safety (HR 0.40; 95% CI 0.16-0.98) and similar composite effectiveness risk (HR 0.96; 95% CI 0.67-1.39).ConclusionUse of direct oral anticoagulants in obese AF patients was associated with a similar effectiveness and safety profile to that of warfarin use.
| S-EPMC9039573 | biostudies-literature
Project description:BackgroundFor patients anticoagulated with direct oral anticoagulants (DOACs) or warfarin and on aspirin (ASA) for nonvalvular atrial fibrillation and/or venous thromboembolism, it is unclear if bleeding outcomes differ.ObjectivesTo assess bleeding rates for ASA with DOACs vs warfarin and one another.MethodsRegistry-based cohort study of patients followed by a 6-center quality improvement collaborative in Michigan using data from 2009 to 2022. The study included adults on ASA with warfarin or DOACs for atrial fibrillation and/or venous thromboembolism without a recent myocardial infarction or heart valve replacement.ResultsAfter propensity matching by anticoagulant class, we compared 2 groups of 1467 patients followed for a median of 18.0 months. Any bleeding and nonmajor bleeding was increased with DOACs + ASA compared with warfarin + ASA (32.2 vs 27.8 and 27.1 vs 22.9 events/100 patient-years; relative risks [RRs], 1.1 and 1.2; 95% CIs, 1.1-1.2 and 1.1-1.3, respectively). After matching by drug, patients on apixaban + ASA vs warfarin + ASA had more bleeding (31.2 vs 27.8 events/100 patient-years; RR, 1.1; 95% CI, 1.0-1.2) and nonmajor bleeding but less major bleeding (3.8 vs 4.7 events/100 patient-years; RR, 0.8; 95% CI, 0.6-1.0) and emergency room visits for bleeding. Patients on rivaroxaban + ASA vs warfarin + ASA had more bleeding (39.3 vs 26.3 events/100 patient-years, RR, 1.5; 95% CI, 1.3-1.6), nonmajor bleeding, and thrombosis. Patients on apixaban + ASA vs rivaroxaban + ASA had significantly less bleeding (22.5 vs 39.3/100 patient-years; RR, 0.6; 95% CI, 0.5-0.7), nonmajor bleeding, major bleeding (2.1 vs 5.5 events/100 patient-years; RR, 0.4; 95% CI, 0.2-0.6), emergency room visits for bleeding, and thrombotic events.ConclusionPatients on DOAC + ASA without a recent myocardial infarction or heart valve replacement had more nonmajor bleeding but otherwise similar outcomes compared with warfarin + ASA. Patients treated with rivaroxaban + ASA experienced more adverse clinical events compared with warfarin + ASA or apixaban + ASA.
| S-EPMC11231707 | biostudies-literature
Project description:Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism.Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016.Setting Community based, using healthcare data from six jurisdictions in Canada and the United States.Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis.Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites.Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients.Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment.Trial registration Clinical trials NCT02833987.
| S-EPMC5641962 | biostudies-literature
Project description:BackgroundThe use of Direct Oral Anticoagulants (DOACs) in patients who have both atrial fibrillation (AF) and end-stage renal disease (ESRD) requiring hemodialysis remains controversial, with warfarin remaining the mainstay of the treatment. As hemodialysis patients were excluded from most clinical DOACs trials, the evidence of their efficacy and safety is lacking in this cohort of patients.AimTo review the current evidence investigating safety profile and the efficacy of DOACs in comparison with warfarin in patients with AF and end-stage renal disease (ESRD) requiring hemodialysis.Methods and resultsWe included five studies with a total of 34,516 patients in our meta-analysis. The outcomes were major bleeding, ischemic stroke, systemic embolization, hemorrhagic stroke, gastrointestinal bleeding, minor bleeding, and death. Of these patients, 31,472 (92.14%) received warfarin and 3,044 patients received DOACs (8.91%). No significant differences in the incidence of hemorrhagic stroke, major bleeding, hemodialysis access site bleeding, ischemic stroke, and GI bleeding were found between DOACs and warfarin. However, there were higher rates of systemic embolization, minor bleeding, and death events in patients who received DOACs than in the warfarin group (3.39% vs. 1.97%, P-value = 0.02), (6.78% vs. 2.2%, P-value 0.02), and (11.38% vs. 5.12%, P-value < 0.006) respectively.ConclusionIn patients on dialysis who require anticoagulation for AF, warfarin could be associated with a significant reduction in minor bleeding, systemic embolization, and death compared to DOACs. These findings need to be validated by further prospective studies to address the best strategy to deal with the increased thrombotic and bleeding risks in such patients.
| S-EPMC9218480 | biostudies-literature
Project description:Background Warfarin, a vitamin K antagonist, has been shown to affect bone mineral density and cause osteoporosis. However, studies investigating the relationship between non-vitamin K antagonist oral anticoagulants (NOACs) and osteoporosis are limited. We thus compared the risk of osteoporosis in patients with atrial fibrillation treated with either NOACs or warfarin. Methods and Results This nationwide, retrospective cohort study used Taiwan's National Health Insurance Research Database. All adult patients in Taiwan who were newly diagnosed with atrial fibrillation and treated with NOACs or warfarin between January 2012 and December 2015 were included and classified into their respective cohorts. Patients who received NOACs were subcategorized into the rivaroxaban, dabigatran, and apixaban subgroups. Propensity score matching was performed for each head-to-head comparison. Adjusted hazard ratios (aHRs) for the risk of osteoporosis were calculated using Cox proportional hazards regression models, with adjustment for confounders. Overall, 17 008 patients were included, with 8504 in each cohort. NOACs were associated with a lower osteoporosis risk than warfarin (aHR=0.82; 95% CI=0.68-0.97). A subgroup effect of treatment duration was identified (namely, the lower osteoporosis risk with NOAC compared with warfarin became stronger in those with longer treatment duration [P for interaction <0.001]). Furthermore, significantly lower risks of osteoporosis were observed in the rivaroxaban (aHR=0.68; 95% CI=0.55-0.83) and apixaban (aHR=0.38; 95% CI=0.22-0.66) subgroups, but not in the dabigatran subgroup (aHR=1.04; 95% CI=0.85-1.27). Conclusions Compared with warfarin, rivaroxaban and apixaban were associated with a significantly lower risk of osteoporosis in patients with atrial fibrillation.
| S-EPMC7033848 | biostudies-literature
Project description:BackgroundIn the pivotal WATCHMAN trials, warfarin was used exclusively for postprocedural anticoagulation following left atrial appendage closure. We sought to investigate the safety and efficacy of direct oral anticoagulants (DOACs) in high-risk patients with atrial fibrillation who underwent left atrial appendage closure with WATCHMAN.MethodsThis was a retrospective study of 318 patients who underwent the WATCHMAN procedure in a tertiary referral center (June 2016-September 2020). We compared the outcomes of patients who were discharged on DOACs versus warfarin after the WATCHMAN procedure. The primary outcome was the composite of any bleeding, thromboembolism, or cardiovascular death through 7 days and 45 days after the procedure.ResultsThe final analysis included 301 patients, of whom 82.4% (248/301) were discharged on DOACs and 17.6% (53/301) were discharged on warfarin. The mean CHA2DS2-VASc and HAS-BLED scores were 4.9 ± 1.6 and 2.9 ± 0.9, respectively. The primary composite outcome was similar between the DOAC and warfarin groups through 7 days (3.2% vs 5.6%; adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.13-3.17; P = .59) and 45 days after procedure (10.1% vs 11.3%; adjusted OR, 1.18; 95% CI, 0.41-3.45; P = .76). Major bleeding (5.2% vs 9.5%; P = .34) and all-cause readmission (12.5% vs 16.9%; P = .85) at 45 days were comparable between the DOAC and warfarin groups. The overall incidence of device-related thrombus and significant peri-device flow at 45 days were low (<0.5%).ConclusionsIn high-risk patients with atrial fibrillation, the primary composite outcome of any bleeding, thromboembolism, or cardiovascular death through 7 days and 45 days following WATCHMAN implantation was similar in patients receiving DOACs versus warfarin.
| S-EPMC11307383 | biostudies-literature
Project description:BackgroundDual antiplatelet therapy and anticoagulants may be required in the case of coexistence of coronary artery disease and atrial fibrillation (AF) undergoing (PCI), with associated increased bleeding rates. The introduction of direct oral anticoagulants (DOACs), however, significantly reduced the incidence of bleeding complications in this clinical setting of patients. We therefore sought to assess whether the recent publication of the AUGUSTUS and ENTRUST-AF PCI studies significantly impacted current evidence on the use of DOACs in AF patients treated with PCI.MethodsWe performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed pooled estimates of risk ratios (RRs) and 95%CIs for any bleeding (AB), cardiovascular events (CVE), and death at follow-up: 12,542 patients have been included in the analysis. We particularly analyzed data comparing dual anti-thrombotic therapy (DOAC plus single anti-platelet therapy) with triple (DOAC plus dual anti-platelet therapy).ResultsWhen compared with patients receiving standard triple therapy with warfarin, patients receiving DOACs had a significantly lower risk of AB (RR 0.65; 95% CI, 0.61-0.70, p < 0.00001) and of MB (RR 0.63; 95% CI, 0.53-0.73, p < 0.00001). The risk of cardiovascular events and mortality were comparable between DOAC and VKA groups (RR 1.05, 95% CI 0.93-1.18, RR 1.14, 95% CI 0.94-1.37, respectively, p n.s.). Similar results were observed comparing triple therapy vs dual therapy.ConclusionsDOACs 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-EPMC7330069 | biostudies-literature