Stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder associated with an increased risk of stroke and systemic embolic events. The prevention of stroke using oral anticoagulants has been a pivotal component of AF management. The purpose of this review is to summarize recent advances in the treatment and prevention of stroke in AF over the last 5 years. We performed a comprehensive structured literature search using MEDLINE for publications from 11th March 2015 through to 31st December 2020. We focused mainly on primarily published research articles and systematic reviews including updates in different international guidelines. We found that improved awareness and detection of AF and use of clinical risk stratification are central to the identification of patients at risk of stroke who would benefit from oral anticoagulation. The recommendation of non-vitamin K antagonist oral anticoagulants over warfarin in both efficacy and safety perspective is represented in all international guidelines. Beyond stroke prevention, there is a move to more holistic or integrated care management of AF, which has been shown to improve outcomes. We conclude that stroke prevention remains a dominant part of the management of patients with AF. Not all stroke risk factors carry equal weight, and many require additional scrutiny (e.g. severity of CAD, type of diabetes, duration of hypertension). The utilization of clinical risk scores to help decision-making should take into account that these scores are mere simplification tools to aid decision-making and the additional clinical benefit with more complex risk scores and addition of biomarkers is limited. Also, stroke and bleeding risks are dynamic and require regular review. Instead of arbitrarily categorizing patients into (artificial) low, moderate, and high stroke risk strata, anticoagulation should be offered to all patients with AF unless they are low risk with no risk factors for stroke. Stroke prevention is also part of the proactive, integrated care approach to holistic management of patients with AF, which can be simplified in the ABC (Atrial fibrillation Better Care) pathway: 'A' Avoid stroke/Anticoagulation; 'B' Better symptom management emphasising patient-centred symptom directed decisions on rate or rhythm control strategies; and 'C' refers to Cardiovascular risk and comorbidity optimization, including lifestyle changes and attention to patient values and preferences, as well as the psychological morbidity associated with AF.

Adherence to the 'Atrial Fibrillation Better Care' Pathway in Patients with Atrial Fibrillation: Impact on Clinical Outcomes-A Systematic Review and Meta-Analysis of 285,000 Patients.

OBJECTIVE: The 'Atrial fibrillation Better Care' (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes. METHODS AND RESULTS: We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies reporting the prevalence of ABC-pathway-adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Meta-analysis of odds ratio (OR) was performed with random-effects models; subgroup analysis and meta-regression were performed to account for heterogeneity. Among the eight studies included, we found a pooled prevalence of ABC-adherent management of 21% (95% confidence interval, CI: 13-34%), with a high grade of heterogeneity, explained by the increasing adherence to each ABC criterion. Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR: 0.42; 95% CI: 0.31-0.56), cardiovascular death (OR: 0.37; 95% CI: 0.23-0.58), stroke (OR: 0.55; 95% CI: 0.37-0.82) and major bleeding (OR: 0.69; 95% CI: 0.51-0.94), with moderate heterogeneity. Prevalence of comorbidities was moderators of heterogeneity for all-cause and cardiovascular death, while longer follow-up was associated with increased effectiveness for all outcomes. CONCLUSION: Adherence to the ABC pathway was suboptimal, being adopted in one in every five patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes.

Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.