Comparative effectiveness and safety of direct oral anticoagulants versus warfarin in UK patients with atrial fibrillation and type 2 diabetes: A retrospective cohort study.
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ABSTRACT: Purpose
To estimate the effectiveness and safety of direct oral anticoagulants (DOACs) compared with warfarin in AF patients with type 2 diabetes (T2DM).Methods
A retrospective cohort study was designed, using the UK Clinical Practice Research Datalink (August 2011-June 2018). Participants were 1-year naïve users of DOACs or warfarin, followed from the date of first prescription of an oral anticoagulant until the end of the study period, death, discontinuation of treatment, switching to another anticoagulant, or an outcome of interest, whichever came first. Cox regression analysis was performed to estimate the hazard ratio (HR) adjusted for potential confounders.Results
A total of 8555 patients were identified. No significant differences were found between DOACs and warfarin in the risk of stroke (adjusted HR 1.15; 95% CI 0.82-1.60), ischemic and unspecified stroke (adjusted HR 1.23; 95% CI 0.86-1.76) or haemorrhagic stroke (adjusted HR 0.75; 95% CI 0.30-1.85), and myocardial infarction (adjusted HR 1.39;95% CI 0.99-1.97). DOAC and warfarin users were comparable with respect to risk of major bleed (adjusted HR 0.83; 95% CI 0.68-1.03), intracranial bleeding (HR 0.66; 95% CI 0.34-1.30), gastrointestinal bleeding (HR 0.88; 95% CI 0.60-1.30), and bleeding on other clinically relevant sites (HR 0.89; 95% CI 0.60-1.31). In the subgroup analyses stratified by gender and diabetes severity, the risk for stroke and bleeding remained consistent.Conclusion
DOACs are effective and safe alternatives to warfarin for the prevention of stroke in AF patients with T2DM.
SUBMITTER: Rustem Gulluoglu F
PROVIDER: S-EPMC8451809 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:BackgroundWhile clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin.MethodsThis retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death.ResultsAmong 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92-2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70-1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59-0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69-0.94]) compared to warfarin users.ConclusionsOlder adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.
| S-EPMC9772095 | biostudies-literature
Project description:Background: Patients with active peptic ulcer (PU) were excluded from direct oral anticoagulant (DOAC) trials for stroke prevention in patients with atrial fibrillation (AF). This study evaluated the safety and effectiveness of DOACs in AF patients with active, inactive and no peptic ulcer (PU). Methods: This study accessed electronic medical records from January 1, 2009 to May 31, 2019 at a multi-center healthcare provider in Taiwan and involved 2,955 AF patients who had undergone esophagogastroduodenoscopy ≤ 1 year before anticoagulation. Subjects were classified into 3 groups: active (n = 237), inactive (n = 828) and no-PU (n = 1,890) groups. We compared the risks of major bleeding, gastrointestinal bleeding, and ischemic stroke/systemic embolism (IS/SE) between DOACs and warfarin among the 3 groups. Results: In the active PU group, there were no significant differences in the risks of major bleeding [hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.08-4.98, p = 0.676], gastrointestinal bleeding (HR = 0.65, 95% CI 0.08-4.98, p = 0.676) and IS/SE (HR = 2.58; 95% CI 0.53-12.70, p = 0.243) between DOAC and warfarin (as the reference). In the inactive PU group, there were no significant differences in the risks of major bleeding (HR = 0.36, 95% CI 0.09-1.39, p = 0.138), gastrointestinal bleeding (HR = 0.21, 95% CI 0.02-1.80, p = 0.153), and IS/SE (HR = 1.04, 95% CI 0.39-2.82, p = 0.934) between DOAC and warfarin (as the reference). In the no-PU group, DOACs were associated with lower risk of major bleeding (HR = 0.26, 95% CI 0.12-0.53, p < 0.001), gastrointestinal bleeding (HR = 0.25, 95% CI 0.01-0.59, p = 0.002), and similar risk of IS/SE (HR = 0.92, 95% CI 0.55-1.54, p = 0.757) compared to warfarin. Conclusions: DOACs were as effective as warfarin in preventing IS/SE irrespective of PU status and safer than warfarin in reducing major bleeding in the no-PU group. In patients with active or inactive PUs, DOAC and warfarin were not significantly different in their effects on major bleeding or gastrointestinal bleeding.
| S-EPMC8732988 | biostudies-literature
Project description:Randomized clinical trials comparing direct oral anticoagulants (DOACs) to warfarin in cancer patients have not been performed. We evaluated the effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of DOACs, in a large population of cancer patients with nonvalvular atrial fibrillation (AF). Using the MarketScan databases, we identified 16?096 AF patients (mean age, 74 years) initiating oral anticoagulant and being actively treated for cancer between 2010 and 2014. Anticoagulant users were matched by age, sex, enrollment date, and drug initiation date. Study end points were identified with diagnostic codes and included ischemic stroke, severe bleeding, other bleeding, and venous thromboembolism (VTE). Cox regression was used to estimate associations of anticoagulants with study end points. Compared with warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users, whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of ischemic stroke did not differ among anticoagulant users. Compared with warfarin, rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07, 0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and severe bleeding than rivaroxaban users. In this population of patients with AF and cancer, DOAC users experienced lower or similar rates of bleeding and stroke compared with warfarin users, and a lower rate of incident VTE.
| S-EPMC5812321 | biostudies-literature
Project description:IntroductionThere is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice.Materials and methodsThis study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB.Results and conclusionsThe final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.
| S-EPMC11315758 | biostudies-literature
Project description:BackgroundAnticoagulation for stroke prevention in atrial fibrillation (AF) has, historically, been under-used in older people. The aim of this study was to investigate prescribing of oral anticoagulants (OACs) for people aged ≥ 75 years in the UK before and after direct oral anticoagulants (DOACs) became available.MethodsA cohort of patients aged ≥ 75 years with a diagnosis of AF was derived from the Clinical Practice Research Datalink (CPRD) between January 1, 2003, and December 27, 2017. Patients were grouped as no OAC, incident OAC (OAC newly prescribed) or prevalent OAC (entered study on OAC). Incidence and point prevalence of OAC prescribing were calculated yearly. The risk of being prescribed an OAC if a co-morbidity was present was calculated; the risk difference (RD) was reported. Kaplan-Meier curves were used to explore persistence with anticoagulation. A Cox regression was used to model persistence with warfarin and DOACs over time.ResultsThe cohort comprised 165,596 patients (66,859 no OAC; 47,916 incident OAC; 50,821 prevalent OAC). Incidence of OAC prescribing increased from 111 per 1000 person-years in 2003 to 587 per 1000 person-years in 2017. Older patients (≥ 90 years) were 40% less likely to receive an OAC (RD -0.40, 95% CI -0.41 to -0.39) than younger individuals (75-84 years). The likelihood of being prescribed an OAC was lower with a history of dementia (RD -0.34, 95% CI -0.35 to -0.33), falls (RD -0.17, 95% CI -0.18 to -0.16), major bleeds (RD -0.17, 95% CI -0.19 to -0.15) and fractures (RD -0.13, 95% CI -0.14 to -0.12). Persistence with warfarin was higher than DOACs in the first year (0-1 year: HR 1.25, 95% CI 1.17-1.33), but this trend reversed by the third year of therapy (HR 0.75, 95% CI 0.63-0.89).ConclusionsOAC prescribing for older people with AF has increased; however, substantial disparities persist with age and co-morbidities. Whilst OACs should not be withheld solely due to the risk of falls, these results do not reflect this national guidance. Furthermore, the under-prescribing of OACs for patients with dementia or advancing age may be due to decisions around risk-benefit management.Trial registrationEUPAS29923 . First registered on: 27/06/2019.
| S-EPMC8406735 | biostudies-literature
Project description:Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285?292 patients were included in the 6 matched cohorts: 57?929 apixaban-warfarin, 26?838 dabigatran-warfarin, 83?007 rivaroxaban-warfarin, 27?096 apixaban-dabigatran, 62?619 apixaban-rivaroxaban, and 27?538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.
| S-EPMC6257512 | biostudies-literature
Project description:BackgroundPrevious studies examining the use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) have largely focused on patients newly initiating therapy. Little is known about the prevalence/patterns of switching to DOACs among AF patients initially treated with warfarin.HypothesisTo examine patterns of anticoagulation among patients chronically managed with warfarin upon the availability of DOACs and identify patient/practice-level factors associated with switching from chronic warfarin therapy to a DOAC.MethodsProspective cohort study of AF patients in the NCDR PINNACLE registry prescribed warfarin between May 1, 2008 and May 1, 2015. Patients were followed at least 1 year (median length of follow-up 375 days, IQR 154-375) through May 1, 2016 and stratified as follows: continued warfarin, switched to DOAC, or discontinued anticoagulation. To identify significant predictors of switching, a three-level multivariable hierarchical regression was developed.ResultsAmong 383 008 AF patients initially prescribed warfarin, 16.3% (n = 62 620) switched to DOACs, 68.8% (n = 263 609) continued warfarin, and 14.8% (n = 56 779) discontinued anticoagulation. Among those switched, 37.6% received dabigatran, 37.0% rivaroxaban, 24.4% apixaban, and 1.0% edoxaban. Switched patients were more likely to be younger, women, white, and have private insurance (all P < .001). Switching was less likely with increased stroke risk (OR, 0.92; 95%CI, 0.91-0.93 per 1-point increase CHA2 DS2 -VASc), but more likely with increased bleeding risk (OR, 1.12; 95%CI, 1.10-1.13 per 1-point increase HAS-BLED). There was substantial variation at the practice-level (MOR, 2.33; 95%CI, 2.12-2.58) and among providers within the same practice (MOR, 1.46; 95%CI, 1.43-1.49).ConclusionsAmong AF patients treated with warfarin between October 1, 2010 and May 1, 2016, one in six were switched to DOACs, with differences across sociodemographic/clinical characteristics and substantial practice-level variation. In the context of current guidelines which favor DOACs over warfarin, these findings help benchmark performance and identify areas of improvement.
| S-EPMC7368350 | biostudies-literature
Project description:We compared the effectiveness and safety of direct oral anticoagulants (DOAC) vs patient self-managed warfarin therapy (PSM) in patients with atrial fibrillation. We linked prospectively registered data from university hospital clinics to nationwide Danish health registries. Primary effectiveness and safety outcomes were ischaemic stroke (incl. systemic embolism) and major bleeding. All-cause mortality and all-cause stroke were secondary outcomes. An inverse probability of treatment propensity-weighted approach was applied to adjust for potential confounding. The study cohorts included 534 patients treated with PSM and 2,671 patients treated with DOAC. Weighted rates of ischaemic stroke were 0.46 and 1.30 percent per year with PSM vs DOAC, hazard ratio (HR) 0.27 (95% confidence interval 0.11-0.68) with 2.5 years follow-up. Rates of major bleeding were 2.32 and 2.13 percent per year (HR 1.06 [0.69-1.63]). All-cause mortality was not statistically different (HR 0.67 [0.39-1.17]), whereas the incidence of all-cause stroke was significantly lower among patients treated with PSM with rates of 0.61 vs 1.45 percent per year (HR 0.36 [0.16-0.78]). In patients with atrial fibrillation, self-managed oral anticoagulant treatment was associated with a significantly lower risk of all-cause and ischaemic stroke compared to treatment with DOAC, whereas no significant differences were observed for major bleeding and mortality.
| S-EPMC6202319 | biostudies-literature
Project description:Background Non-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown. Methods We retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death. Results The mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56–2.34), major bleeding (HR 0.80, 95% CI 0.32–2.03) and all-cause death (HR 1.09, 95% CI 0.73–1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76–1.47). These outcomes were not different in various subgroups analyzed. Conclusion In this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV.
| S-EPMC9197068 | biostudies-literature