Are direct oral anticoagulants (DOACs) more effective in lowering the risk of significant bleeding episodes in patients with non valvular atrial fibrillation?
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- Answered 26 Jan 2020 Conflict of interest declaration: None In answering this I’ve assumed DOACs are the same as NOACs. In 2017 the Belgian Health Care Knowledge Centre published “Anticoagulants in non-valvular atrial fibrillation”  and this includes section 4 'efficacy and safety of NOACS' which can be read via the link below. A 2019 PLOS ONE article “Association of stroke and bleed events in nonvalvular atrial fibrillation patients with direct oral anticoagulant prescriptions in NHS England between 2013 and 2016” . In the discussion they report: “Our analysis showed a 50% reduction in strokes, both ischaemic and haemorrhagic, with DOAC prescription compared to warfarin. However, a small but non-significant reduction in bleed risk, both clinically relevant and GI, was observed with DOAC prescription compared to warfarin. Stratification by sex and age showed stroke or bleed risk reduction in specific sub-groups compared to warfarin, in particular reduction in stroke risk for males and patients with age between 70–89 years, and reduction in bleed risk in patients with age between 70–79 years only.” The 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation  discusses individual DOACs, including this section: “Most NOACs represent an advance in therapeutic safety when compared with warfarin for prevention of thromboembolism in patients with AF. The NOAC AF trials demonstrated that NOACs are noninferior (S126.96.36.199-1, S188.8.131.52-2) or superior (S184.108.40.206-3, S220.127.116.11-4) to warfarin in preventing stroke or thromboembolism. NOACs reduce intracranial bleeding as compared with warfarin (S18.104.22.168-1–S22.214.171.124-5). Although no direct RCT data are available, limited data comparing individual NOACs to one another are emerging from meta-analyses of the original NOAC clinical trials (S126.96.36.199-6) and registries and patient databases (S188.8.131.52-6–S184.108.40.206-14), and more data are expected. Specific NOACs, such as apixaban, may have lower risks of bleeding (including intracranial hemorrhage) and improved efficacy for stroke prevention, whereas the risk of bleeding for rivaroxaban is comparable to that of warfarin.” A 2018 BMJ paper “Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care”  reported: “Results In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58). Conclusions Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin.” Finally a 2018 paper in Open Heart, “Direct oral anticoagulants versus warfarin: is new always better than the old?”  offers some caution, reporting: “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.” References 1) https://kce.fgov.be/sites/default/files/atoms/files/KCE_279_Novel_Anticoagulants_Report.pdf 2) https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0218878&type=printable 3) http://www.onlinejacc.org/content/accj/early/2019/01/21/j.jacc.2019.01.011.full.pdf?_ga=2.192299885.630206267.1550301018-1833835119.1547724626 4) https://www.bmj.com/content/362/bmj.k2505 5) https://openheart.bmj.com/content/5/1/e000712