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Direct oral anticoagulants versus warfarin: is new always better than the old?

ABSTRACT: About 1.4 British million people are at risk of strokes due to non-valvular atrial fibrillation (AF) necessitating long-term anticoagulation. The vitamin K antagonist, warfarin, has a long half-life and narrow therapeutic range necessitating regular monitoring and is a common cause of iatrogenic hospital admission. Direct-acting oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban are not required to have monitoring but are sensitive to changes in renal function and are associated with poorer adherence. There are good grounds to believe that DOACs are not always superior to warfarin in routine practice particularly with an older population. Much higher levels of therapeutic effectiveness can be achieved using a simple genotype guidance to identify those who are highly sensitive and by adoption of home monitoring. These adjustments could make warfarin the preferred drug for most people and would reduce the dramatic rise in health service expenditure.

SUBMITTER: Burn J

PROVIDER: S-EPMC5845414 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Direct oral anticoagulants versus warfarin: is new always better than the old?

Burn John J Pirmohamed Munir M

Open heart 20180207 1

About 1.4 British million people are at risk of strokes due to non-valvular atrial fibrillation (AF) necessitating long-term anticoagulation. The vitamin K antagonist, warfarin, has a long half-life and narrow therapeutic range necessitating regular monitoring and is a common cause of iatrogenic hospital admission. Direct-acting oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban are not required to have monitoring but are sensitive to changes in renal function and are as ...[more]

PMID: 29531758

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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).

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.

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Direct oral anticoagulants versus warfarin: is new always better than the old?

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Direct oral anticoagulants versus warfarin: is new always better than the old?

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