Dataset Information

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

ABSTRACT:

Objective

To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation.

Design

Observational nationwide cohort study.

Setting

Three Danish nationwide databases, August 2011 to October 2015.

Participants

61?678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35?436, 57%), dabigatran 150 mg (n=12?701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%).

Main outcome measures

Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding.

Results

When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5.3%).

Conclusion

All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting. No significant difference was found between NOACs and warfarin for ischaemic stroke. The risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin.

SUBMITTER: Larsen TB

PROVIDER: S-EPMC4910696 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

Larsen Torben Bjerregaard TB Skjøth Flemming F Nielsen Peter Brønnum PB Kjældgaard Jette Nordstrøm JN Lip Gregory Y H GY

BMJ (Clinical research ed.) 20160616

<h4>Objective</h4> To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation.<h4>Design</h4> Observational nationwide cohort study.<h4>Setting</h4> Three Danish nationwide databases, August 2011 to October 2015.<h4>Participants</h4> 61 678 patients with non-valvular atrial fibrillation who were naïve to oral antic ...[more]

PMID: 27312796

Similar Datasets

Project description:Objective To examine clinical effectiveness and safety of apixaban 2.5 mg, dabigatran 110 mg, and rivaroxaban 15 mg compared with warfarin among patients with atrial fibrillation who had not previously taken an oral anticoagulant.Design Propensity weighted (inverse probability of treatment weighted) nationwide cohort study.Setting Individual linked data from three nationwide registries in Denmark.Participants Patients with non-valvular atrial fibrillation filling a first prescription for an oral anticoagulant from August 2011 to February 2016. Patients who filled a prescription for a standard dose non-vitamin K antagonist oral anticoagulant (novel oral anticoagulants, NOACs) were excluded. To control for baseline differences in the population, a propensity score for receipt of either of the four treatment alternatives was calculated to apply an inverse probability treatment weight.Intervention Initiated anticoagulant treatment (dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and warfarin).Main outcome measures Patients were followed in the registries from onset of treatment for the primary effectiveness outcome of ischaemic stroke/systemic embolism and for the principal safety outcome of any bleeding events.Results Among 55 644 patients with atrial fibrillation who met inclusion criteria, the cohort was distributed according to treatment: apixaban n=4400; dabigatran n=8875; rivaroxaban n=3476; warfarin n=38 893. The overall mean age was 73.9 (SD 12.7), ranging from a mean of 71.0 (warfarin) to 83.9 (apixaban). During one year of follow-up, apixaban was associated with higher (weighted) event rate of ischaemic stroke/systemic embolism (4.8%), while dabigatran, rivaroxaban, and warfarin had event rates of 3.3%, 3.5%, and 3.7%, respectively. In the comparison between a non-vitamin K antagonist oral anticoagulant and warfarin in the inverse probability of treatment weighted analyses and investigation of the effectiveness outcome, the hazard ratios were 1.19 (95% confidence interval 0.95 to 1.49) for apixaban, 0.89 (0.77 to 1.03) for dabigatran, and 0.89 (0.69 to 1.16) for rivaroxaban. For the principal safety outcome versus warfarin, the hazard ratios were 0.96 (0.73 to 1.27) for apixaban, 0.80 (0.70 to 0.92) for dabigatran, and 1.06 (0.87 to 1.29) for rivaroxaban.Conclusion In this propensity weighted nationwide study of reduced dose non-vitamin K antagonist oral anticoagulant regimens, apixaban 2.5 mg twice a day was associated with a trend towards higher rates of ischaemic stroke/systemic embolism compared with warfarin, while rivaroxaban 15 mg once a day and dabigatran 110 mg twice a day showed a trend towards lower thromboembolic rates. The results were not significantly different. Rates of bleeding (the principal safety outcome) were significantly lower for dabigatran, but not significantly different for apixaban and rivaroxaban compared with warfarin.

Project description:Background It is unclear whether nonvitamin K antagonist oral anticoagulants ( NOAC s) can mitigate dementia development in atrial fibrillation. We compared dementia development among users of NOACs or warfarin in patients with atrial fibrillation with no prior neurological diagnoses. Methods and Results We conducted a Danish nationwide cohort study including 33 617 new oral anticoagulant users with nonvalvular atrial fibrillation, of which 11 052 were aged 60 to 69 years, 13 237 were aged 70 to 79 years, and 9238 were aged 80 years and older. To exclude prevalent non -oral anticoagulants- associated dementia, we considered the at-risk population of patients alive and free of dementia at 180 days following inclusion. We compared rates of new-onset dementia by age and treatment regimen using inverse probability of treatment weighting to account for confounding. Approximately 60% of patients were NOAC users and 40% were warfarin users. Mean follow-up was 3.4 years. Dementia occurred in 41 patients aged 60 to 69 years, 276 patients aged 70 to 79 years, and 441 patients aged 80 years and older. Relative to warfarin users, dementia rates were nonsignificantly lower among NOAC users aged 60 to 69 years (0.11 events/100 person-years versus 0.12 events/100 person-years; weighted hazard ratio, 0.92 [95% CI, 0.48-1.72]) and NOAC users aged 70 to 79 years (0.64 events/100 person-years versus 0.78 events/100 person-years; weighted hazard ratio , 0.86 [95% CI, 0.68-1.09]), whereas NOAC s were associated with significantly higher dementia rates (2.16 events/100 person-years versus 1.70 events/100 person-years; weighted hazard ratio , 1.31 [95% CI, 1.07-1.59]) in patients 80 years and older. Conclusions This nationwide cohort of patients with atrial fibrillation revealed no clinically meaningful difference in dementia development between users of NOACs or warfarin apart from a higher risk in NOAC users 80 years and older, which may relate to residual confounding from selective prescribing and unobserved comorbidities.

Project description:AimsUsing Scandinavian population-based registries, we assessed risk of stroke/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in anticoagulation-naïve patients with atrial fibrillation (AF).Methods and resultsThis historical cohort study included 219 545 AF patients [median age 74 years; 43% women; mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65-74 years, sex category) score 3.3] initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden (1 January 2013 to 31 December 2016). The primary endpoints were stroke/SE and major bleeding. The median follow-up times were 9.7 (3.9-21.5) months for stroke/SE and 9.6 (3.8-21.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban-warfarin (n = 111 162), dabigatran-warfarin (n = 56 856), and rivaroxaban-warfarin (n = 61 198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke/SE, adjusted HRs against warfarin were 0.96 [95% confidence interval (CI): 0.87-1.06] for apixaban, 0.89 (95% CI: 0.80-1.00) for dabigatran, and 1.03 (95% CI: 0.92-1.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI: 0.67-0.78) for apixaban, 0.89 (95% CI: 0.82-0.97) for dabigatran, and 1.15 (95% CI: 1.07-1.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dose-defined subgroups.ConclusionIn this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke/SE to patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin.

Project description:Background Vitamin K antagonists (VKAs) are associated with coronary artery calcification in low-risk populations, but their effect on calcification of large arteries remains uncertain. The effect of non-vitamin K antagonist oral anticoagulants (NOACs) on vascular calcification is unknown. We investigated the influence of use of VKA and NOAC on calcification of the aorta and aortic valve. Methods In patients with atrial fibrillation without a history of major adverse cardiac or cerebrovascular events who underwent computed tomographic angiography, the presence of ascending aorta calcification (AsAC), descending aorta calcification (DAC), and aortic valve calcification (AVC) was determined. Confounders for VKA/NOAC treatment were identified and propensity score adjusted logistic regression explored the association between treatment and calcification (Agatston score > 0). AsAC, DAC, and AVC differences were assessed in propensity score-matched groups. Results Of 236 patients (33% female, age: 58 ± 9 years), 71 (30%) used VKA (median duration: 122 weeks) and 79 (34%) used NOAC (median duration: 16 weeks). Propensity score-adjusted logistic regression revealed that use of VKA was significantly associated with AsAC (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.16-4.59; p = 0.017) and DAC (OR: 2.38; 95% CI: 1.22-4.67; p = 0.012) and a trend in AVC (OR: 1.92; 95% CI: 0.98-3.80; p = 0.059) compared with non-anticoagulation. This association was absent in NOAC versus non-anticoagulant (AsAC OR: 0.51; 95% CI: 0.21-1.21; p = 0.127; DAC OR: 0.80; 95% CI: 0.36-1.76; p = 0.577; AVC OR: 0.62; 95% CI: 0.27-1.40; p = 0.248). A total of 178 patients were propensity score matched in three pairwise comparisons. Again, use of VKA was associated with DAC ( p = 0.043) and a trend toward more AsAC ( p = 0.059), while use of NOAC was not (AsAC p = 0.264; DAC p = 0.154; AVC p = 0.280). Conclusion This cross-sectional study shows that use of VKA seems to contribute to vascular calcification. The calcification effect was not observed in NOAC users.

Dataset Information

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

Objective

Design

Setting

Participants

Main outcome measures

Results

Conclusion

Publications

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets