Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation

Abstract

Background: The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remains uncertain. Purpose: To compare the available treatment strategies in patients with AF. Data Sources: English-language studies in multiple databases from January 1, 2000, to February 14, 2018. Study Selection: Two reviewers independently screened citations for studies examining treatments for stroke prevention in patients with AF. Data Extraction: Two reviewers independently abstracted data and assessed study quality and applicability. Data Synthesis: Data from 220 articles were included. Dabigatran and apixaban were superior while rivaroxaban and edoxaban were similar to warfarin in the prevention of stroke or systemic embolism. Apixaban and edoxaban were superior while rivaroxaban and dabigatran were similar to warfarin in reducing the risk of major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction p>0.05) and patients less than 75 years old had lower rates of bleeding with dabigatran (interaction p<0.001). The benefit of treatment with apixaban was consistent in many subgroups including those with renal impairment, diabetes and prior stroke (interaction p>0.05 for all). The greatest bleeding risk reduction was observed in patients with GFR<50mL/min (p=0.003). Similar treatment effects of rivaroxaban and edoxaban were observed in patients with prior stroke, diabetes, or heart failure (interaction p>0.05 for all). Limitations: Heterogeneous study populations, interventions and outcomes. Conclusion: The available DOACs are at least as effective and safe when compared to warfarin. Similar benefits of treatment with DOACs were observed across multiple patient subgroups of interest, giving assurance to the safe and efficacious use of DOACs for a wide range of patients with AF. Primary Funding Source: Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999)

Comparative effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in nonvalvular atrial fibrillation: a Canadian multicentre observational cohort study

“…Recent meta-analyses of observational studies showed either a similar or a lower risk of stroke associated with DOAC use compared to warfarin, with heterogeneity regarding which DOAC was associated with reduced risk of stroke. 10,13,14 A large observational study from Sweden, in which warfarin-exposed patients had a time in therapeutic range of international normalized ratio measurements of Research 71.4%, also showed a similar HR for ischemic strokes for DOACs and warfarin. 34 In their recent observational studies, however, both Lip and colleagues 35 and Graham and colleagues 36 reported decreased risk of stroke with all 3 DOACs compared to warfarin.…”

“…34 In their recent observational studies, however, both Lip and colleagues 35 and Graham and colleagues 36 reported decreased risk of stroke with all 3 DOACs compared to warfarin. Recent meta-analyses showed similar major bleeding risks with rivaroxaban compared to warfarin, 10,11,13,14 lower or similar major bleeding risk with dabigatran, 10,11,13 and lower major bleeding risk with apixaban. 10,11,13 The finding that is most consistent across the literature is that of lower intracranial bleeds with DOACs than with warfarin.…”

“…Recent meta-analyses showed similar major bleeding risks with rivaroxaban compared to warfarin, 10,11,13,14 lower or similar major bleeding risk with dabigatran, 10,11,13 and lower major bleeding risk with apixaban. 10,11,13 The finding that is most consistent across the literature is that of lower intracranial bleeds with DOACs than with warfarin. 11,13,14,36,37 Increased mortality in warfarin cohorts was also reported in a network meta-analysis of 18 randomized controlled trials, as well as in a large recent observational study.…”

Rivaroxaban for the treatment of cerebral venous thrombosis

“…Over the last decades, Novel Oral Anticoagulants (NOACs) such as Rivaroxaban might offer a convenient alternative to Warfarin in some thrombotic and thromboembolic disorders [7,8] Some evidence shows that NOACs generally reduce the potential risks of major and fatal hemorrhages, the major adverse event of anticoagulant drugs, compared to vitamin-K antagonists [9][10][11]. Some reports have shown that Rivaroxaban has a therapeutic effect equivalent to Warfarin in deep vein thrombosis and pulmonary embolism [12,13].…”

Elderly people are inherently sensitive to the pharmacological activity of rivaroxaban: implications for DOAC prescribing

“…Bleeding associated with anticoagulation therapy remains a major concern for clinicians and patients. Whilst quantification of the risk of bleeding has been inconsistent due to differences in study sample sizes, patient populations and time frames, studies with DOACs in general indicate an increased risk of gastrointestinal hemorrhage and a lower risk of intracranial bleeding compared to warfarin [ 8 ] and with apixaban and edoxaban being superior to rivaroxaban, dabigatran and warfarin in reducing the risk of major bleeding [ 9 ].…”