Mobile health-technology integrated care in atrial fibrillation patients with heart failure: A report from the mAFA-II randomized clinical trial.

BACKGROUND: To assess the effect of mobile health (mHealth) technology-implemented 'Atrial fibrillation Better Care' (ABC) pathway-approach (mAFA intervention) in AF patients with Heart Failure (HF). METHODS: From the Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) cluster randomized trial, we evaluated the effect of mAFA intervention on the risk of major outcomes in patients with HF using Inverse Probability of Treatment Weighting. Primary outcome was the composite outcome of stroke/thromboembolism, all-cause death, and rehospitalization. The effect of mAFA and the interaction with HF at baseline was assessed through Cox-regressions. RESULTS: Among the 3,324 patients originally enrolled in the trial, 714 (21.5%; mean age: 72.7±13.1 years; 39.9% females) had HF. The effect of mAFA intervention on the primary outcome was consistent in patients with and without HF (Hazard Ratio, (HR): 0.59, 95% Confidence Interval (CI): 0.29-1.22 vs. HR: 0.40, 95%CI: 0.21-0.76, p for interaction=0.438); similar findings were found for rehospitalisations and bleeding events. A trend towards lower efficacy of mAFA in HF patients was observed for all-cause death, while the risk of the composite outcome of 'recurrent AF, HF and acute coronary syndrome' was higher among AF-HF patients allocated to mAFA (p for interaction: <0.001). CONCLUSION: A mHealth-technology implemented ABC pathway provides consistent effects on the risks of primary outcome, rehospitalisation and bleeding, in AF patients both with and without HF. However, AF-HF patients may need tailored approaches to improve their overall prognosis, specifically to reduce the risk of recurrent AF, HF and acute coronary syndrome.

Frailty prevalence and impact on outcomes in patients with atrial fibrillation: A systematic review and meta-analysis of 1,187,000 patients.

Frailty is a clinical syndrome characterized by a reduced physiologic reserve, increased vulnerability to stressors and an increased risk of adverse outcomes. People with atrial fibrillation (AF) are often burdened by frailty due to biological, clinical, and social factors. The prevalence of frailty, its management and association with major outcomes in AF patients are still not well quantified. We systematically searched PubMed and EMBASE, from inception to September 13th, 2021, for studies reporting the prevalence of frailty in AF patients. The study was registered in PROSPERO (CRD42021235854). 33 studies were included in the systematic review (n = 1,187,651 patients). The frailty pooled prevalence was 39.7 % (95 %CI=29.9 %-50.5 %, I2 =100 %), while meta-regression analyses showed it is influenced by age, history of stroke, and geographical location. Meta-regression analyses showed that OAC prescription was influenced by study-level mean age, baseline thromboembolic risk, and study setting. Frail AF patients were associated with a higher risk of all-cause death (OR=5.56, 95 %CI=3.46-8.94), ischemic stroke (OR=1.59, 95 %CI=1.00-2.52), and bleeding (OR=1.64, 95 %CI=1.11-2.41), when compared to robust individuals. In this systematic review and meta-analysis, the prevalence of frailty was high in patients with AF. Frailty may influence the prognosis and management of AF patients, thus requiring person-tailored interventions in a holistic or integrated approach to AF care.

Polypharmacy in Older People With Heart Failure: Roles of the Geriatrician and Pharmacist.

Heart failure (HF) is a common health condition that typically affects older adults. Many people with HF are cared for on an inpatient basis, by noncardiologists, such as acute medical physicians, geriatricians and other physicians. Treatment options for HF are ever increasing, and adherence to guidelines for prognostic therapy contributes to polypharmacy, which is very familiar to clinicians who care for older people. This article explores the recent trials in both HF with reduced ejection fraction and HF with preserved ejection fraction and the limitations of international guidance in their management with respect to older people. In addition, this article discusses the challenge of managing polypharmacy in those with advanced age, and the importance of involving a geriatrician and pharmacist in the HF multidisciplinary team to provide a holistic and person-centred approach to optimisation of HF therapies.

Anticoagulation versus placebo for heart failure in sinus rhythm.

BACKGROUND: People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population. OBJECTIVES: To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm. SEARCH METHODS: We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020. We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month. We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI). MAIN RESULTS: We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect on all-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin may increase the risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxaban makes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR 0.67, 95% CI 0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR 1.65, 95% CI 1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Based on the three RCTs, there is no evidence that oral anticoagulant therapy modifies mortality in people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events. There is no evidence of a difference in the effect of rivaroxaban on all-cause death compared to placebo. It probably reduces the risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.

Beyond the 2020 guidelines on atrial fibrillation of the European society of cardiology.

The most recent atrial fibrillation (AF) guidelines delivered by European Society of Cardiology (ESC) offer an updated approach to AF management, with the perspective of improved characterization of the arrhythmia, the cardiac substrate and the patients profile in terms of associated risk factors and comorbidities. Recommendations were based on careful scrutiny and assessment of all available evidence with the final aim to offer to practitioners a lower level of uncertainty in the complex process of decision making for patients with AF. The 2020 ESC guidelines on AF propose a paradigm shift in the clinical approach to AF patients, moving from a single-domain AF classification to comprehensive characterization of AF patients. Given the complex nature of AF, an integrated holistic management of AF patients is suggested by the guidelines for improving patients outcomes through the formal introduction of the CC (Confirm AF and Characterize AF) to ABC (Atrial fibrillation Better Care) pathway. In line with this concept, these new guidelines underline the importance of a more comprehensive management of AF patients which should not be limited to simply prescribe oral anticoagulation or decide between a rhythm or rate control strategy. Indeed, each step of the ABC pathway represents one of the pivotal pillars in the management of AF and only a holistic approach has the potential to improve patients' outcomes. In this review we will discuss the background that supports some of the new recommendations of 2020 ESC guidelines, with important implications for daily management of AF patients.

Association between clinical risk scores and mortality in atrial fibrillation: Systematic review and network meta-regression of 669,000 patients.

AIMS: Many clinical scores for risk stratification in patients with atrial fibrillation have been proposed, and some have been useful in predicting all-cause mortality. We aim to analyse the relationship between clinical risk score and all-cause death occurrence in atrial fibrillation patients. METHODS: We performed a systematic search in PubMed and Scopus from inception to 22 July 2017. We considered the following scores: ATRIA-Stroke, ATRIA-Bleeding, CHADS2, CHA2DS2-VASc, HAS-BLED, HATCH and ORBIT. Papers reporting data about scores and all-cause death rates were considered. RESULTS: Fifty studies and 71 scores groups were included in the analysis, with 669,217 patients. Data on ATRIA-Bleeding, CHADS2, CHA2DS2-VASc and HAS-BLED were available. All the scores were significantly associated with an increased risk for all-cause death. All the scores showed modest predictive ability at five years (c-indexes (95% confidence interval) CHADS2: 0.64 (0.63-0.65), CHA2DS2-VASc: 0.62 (0.61-0.64), HAS-BLED: 0.62 (0.58-0.66)). Network meta-regression found no significant differences in predictive ability. CHA2DS2-VASc score had consistently high negative predictive value (≥94%) at one, three and five years of follow-up; conversely it showed the highest probability of being the best performing score (63% at one year, 60% at three years, 68% at five years). CONCLUSION: In atrial fibrillation patients, contemporary clinical risk scores are associated with an increased risk of all-cause death. Use of these scores for death prediction in atrial fibrillation patients could be considered as part of holistic clinical assessment. The CHA2DS2-VASc score had consistently high negative predictive value during follow-up and the highest probability of being the best performing clinical score.

Safety of direct oral anticoagulants in real-world clinical practice: translating the trials to everyday clinical management.

INTRODUCTION: Direct oral anticoagulants (DOACs) may be regarded as some of the most successful innovations in recent times. These drugs which were specifically developed to overcome the challenges posed by warfarin did just that and in the process, have changed the outlook towards stroke prevention with anticoagulation. The decade of experience with these drugs that has resulted in the availability of large scale data on their safety profile has aided this. Areas covered: This review examines existing real-world studies (RWS) and their interpretation to better appreciate how they either complement or contradict findings from the hallmark trials. Specific focus has been made on the safety of DOACs, on their risks of major bleeding, intra-cranial haemorrhage (ICH), gastro-intestinal (GI) bleeding and all-cause mortality compared to warfarin and each other. DOAC use in the elderly and other sub-groups are briefly discussed. Expert opinion: Results for safety outcomes according to 'real world evidence' (RWE) are in-keeping with randomised controlled trials (RCTs) and currently, all 4 DOACs have been deemed at least as effective as warfarin, while demonstrating superiority in some aspects. While real world studies act as a complementary source of knowledge, traditional RCTs remain the gold standard for determining cause-effect relationships.

ABC (Atrial fibrillation Better Care) Pathway and Healthcare Costs in Atrial Fibrillation: The ATHERO-AF Study.

BACKGROUND: The Atrial fibrillation Better Care (ABC) pathway has been proposed to streamline patient management in an integrated, holistic manner. Compliance to ABC resulted in lower incidence of cardiovascular events, but its impact on health-related costs has not been evaluated. METHODS: Exploratory analysis of costs related to cardiovascular events in the ATHERO-AF prospective cohort study including atrial fibrillation patients on vitamin K antagonists. A Diagnosis-Related Group code provided by the Italian Ministry of Health was assigned to each event to estimate the relative cost. The analysis was performed by dividing patients according to ABC pathway components. RESULTS: Overall, 118 cardiovascular events incurred a cost of 1,017,354 euros (1,149,610 USD). The mean total costs were 13,050 (14,747 USD) and 11,218 euros (12,676 USD) for a non-fatal cardiac event or ischaemic stroke, respectively. The cost-saving was 719 euros (813 USD) per patient-year for patients in group A vs non-A, 703 euros (794 USD) for B vs non-B, 480 euros (542 USD) for C vs non-C and 2776 euros (3,137 USD) for ABC vs non-ABC. The cost per event increased with the number of uncontrolled ABC components: 507 euros (573 USD) for 1, 965 euros (1,091 USD) for 2 and 3,431 euros (3,877 USD) for patients not having any of the three components of the ABC. CONCLUSIONS: Management of atrial fibrillation patients according to the ABC pathway was associated with significantly lower health-related costs. Application of the ABC pathway may help reduce healthcare costs related to cardiovascular events in this high-risk patient population.

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

BACKGROUND: Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. METHODS: Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. RESULTS: The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). CONCLUSIONS: The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF.

Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.

Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 µg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 µg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs. Restriction of dietary vitamin K intake does not seem to be a valid strategy to improve anticoagulation quality with VKAs. It would be, perhaps, more relevant to maintain stable dietary habit, avoiding wide changes in the intake of vitamin K.

Stroke prevention.

INTRODUCTION: People with a history of stroke or transient ischaemic attack are at high risk of all vascular events, such as myocardial infarction (MI), but are at particular risk of subsequent stroke (about 10% in the first year and about 5% each year thereafter). METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in people with previous stroke or transient ischaemic attack? What are the effects of preventive anticoagulant and antiplatelet treatments in people with atrial fibrillation and either with or without previous stroke or transient ischaemic attack? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2006 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 120 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: alternative antiplatelet regimens to aspirin, anticoagulation (oral dosing, or in those with sinus rhythm), aspirin (high-dose, or low-dose aspirin), blood pressure reduction, carotid and vertebral percutaneous transluminal angioplasty, carotid endarterectomy (in people: with asymptomatic but severe carotid artery stenosis; with less than 30% symptomatic carotid artery stenosis; with moderate [30-49%] symptomatic carotid artery stenosis; with moderately severe [50-69%] symptomatic carotid artery stenosis; with severe [more than 70%] symptomatic carotid artery stenosis; or with symptomatic near occlusion of the carotid artery), cholesterol reduction, vitamin B suppliments (including folate), or different blood pressure-lowering regimens.