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Atrial fibrillation (AF) and stroke prevention remain topics of major interest, especially the discussion regarding anticoagulation and whom and how best to treat.1–5 This special issue of the journal highlights some of the current considerations and issues regarding AF and stroke prevention.
Stroke risk is estimated according to a scoring system, usually the CHA2DS2-VASC score.6–8 In the first paper of this issue, Lee et al. highlight the relative importance of the individual risk factors for stroke, showing that calculation of individual risk as opposed to average risk can improve risk estimates.
Menichelli et al. compare different direct oral anticoagulants (DOACs) for safety and efficacy in a large network meta-analysis of 605 771 patients. Although the study was based on observational and not randomized data, the analysis provides external validation to the findings of the major randomized trials. Another large observational meta-analysis (440 281 patients) looks at older (≥75 years) patients. Here, Silverio et al. found that DOACs were associated with a lower risk of stroke or systemic embolism, intracranial bleeding, and fatal bleeding than vitamin K antagonists; gastrointestinal bleeding rates were higher.
The Edoxaban Treatment in Routine Clinical Practice for Patients with Non-Valvular Atrial Fibrillation (ETNA-AF Europe) is a contemporary prospective, multi-centre, post-EMA authorization, observational study. ETNA-AF enrolled patients treated with edoxaban in 10 European countries: 13 092 patients completed 1-year follow-up, and De Groot et al. report that the rates of stroke, systemic embolism, and major bleeding were low in this cohort of high-risk but properly selected AF patients.
Plitt et al. present a very important meta-analysis of 58 634 patients with diabetes and AF, from the four major randomized controlled trials comparing DOACs with vitamin K antagonists. DOACs reduced the risk of stroke/systemic embolism in diabetic patients (hazard ratio 0.80; 95% confidence interval 0.69–0.93) to a similar degree as in patients without diabetes (hazard ratio 0.82; 95% confidence interval0.74–0.91) (P-interact 0.81). Importantly, there was no difference in the effect of DOACs vs. warfarin on major bleeding (diabetes: hazard ratio 0.95, 95% confidence interval 0.75–1.20; no diabetes: hazard ratio 0.83, 95% confidence interval 0.55–1.24; P-interact 0.37). This meta-analysis firmly establishes DOACs as the treatment of choice for anticoagulation in diabetic patients with AF.
The ‘double-triple conundrum’, the challenge of antithrombotic therapy in patients with AF undergoing percutaneous coronary intervention (often in the circumstances of an acute coronary syndrome),9,10 is addressed by Gargiulo et al. in a meta-analysis of the four major DOAC-based randomized clinical trials. The report includes 10 193 patients, of whom 5675 presented with an acute coronary syndrome (ACS) and 4518 with a chronic coronary syndrome (CCS). The primary bleeding endpoint was lower with dual antithrombotic therapy (DAT) compared with triple antithrombotic therapy (TAT) antithrombotic therapy in both ACS (12.2% vs. 19.4%) and CCS (14.6% vs. 22.0%). There was no difference between DAT and TAT for all-cause death, major adverse cardiovascular events, or stroke. However, it may be important that myocardial infarction and stent thrombosis rates were numerically higher with DAT.
DOACs are simple to use, but there are no everyday markers to verify patient compliance. Tzikas et al. report that a patient-centred, physician-led integrated motivational intervention improved adherence to anticoagulant therapy. Komen et al. report on 21 028 AF patients from the Stockholm Healthcare database that persistence rates, defined as continuing to claim DOAC prescriptions within a 90-day gap, decreased to 70% at the end of follow-up. As expected, non-persistence and poor adherence were associated with an increased stroke risk.
Comorbidities often complicate anticoagulation. Proietti et al. discuss the impact of liver disease in 16 168 (4.1%) of 393 507 patients with AF. Liver disease patients were less often treated with oral anticoagulants (odds ratio 0.96, 95% confidence interval 0.92–0.98) and carried a higher risk for all clinical outcomes. Nonetheless, use of oral anticoagulants in liver disease AF patients was associated with a significant benefit/risk ratio.
The last subject in this issue is valvular AF. In a Danish nationwide cohort study, Strange et al. found no difference in the risks of all-cause mortality, stroke, and bleeding in patients with AF and valve disease selected for treatment with vitamin K antagonists compared with those selected for Factor Xa inhibitors. Also, from Danish registries, Melgaard et al. report on 10 043 patients with different valve diseases: 5190 (51.7%) with aortic stenosis, 1788 (17.8%) aortic regurgitation, 327 (3.3%) mitral stenosis, and 2738 (27.3%) mitral regurgitation. Patients with aortic stenosis or mitral stenosis were high-risk subgroups. At 1 year, the risk of thromboembolism was 4.6% in patients with mitral stenosis (they received vitamin K antagonists) and 2.6% in patients with aortic stenosis (receiving vitamin K antagonist or DOAC), while for patients with aortic or mitral regurgitation, the risks of thromboembolism were lower (1.5–1.8%). Major bleeding was also higher in patients with aortic stenosis or mitral stenosis than in patients with aortic or mitral regurgitation.
