Rhythm Control in Heart Failure Patients With Atrial Fibrillation Contemporary Challenges Including the Role of Ablation

AbstractBecause nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure

Do Omega-3 fatty acids prevent atrial fibrillation after open heart surgery? A meta-analysis of randomized controlled trials

OBJECTIVES: N-3 polyunsaturated fatty acids have been proposed as a novel treatment for preventing postoperative atrial fibrillation due to their potential anti-inflammatory and anti-arrhythmic effects. However, randomized studies have yielded conflicting results. The objective of this study is to review randomized trials of N-3 polyunsaturated fatty acid use for postoperative atrial fibrillation. METHODS: Using the CENTRAL, PUBMED, EMBASE, and LILACS databases, a literature search was conducted to identify all of the studies in human subjects that reported the effects of N-3 polyunsaturated fatty acids on the prevention of postoperative atrial fibrillation in cardiac surgery patients. The final search was performed on January 30, 2011. There was no language restriction, and the search strategy only involved terms for N-3 polyunsaturated fatty acids (or fish oil), atrial fibrillation, and cardiac surgery. To be included, the studies had to be randomized (open or blinded), and the enrolled patients had to be >18 years of age. RESULTS: Four randomized studies (three double-blind, one open-label) that enrolled 538 patients were identified. The patients were predominantly male, the mean age was 62.3 years, and most of the patients exhibited a normal left atrial size and ejection fraction. N-3 polyunsaturated fatty acid use was not associated with a reduction in postoperative atrial fibrillation. Similar results were observed when the open-label study was excluded. CONCLUSIONS: There is insufficient evidence to suggest that treatment with N-3 polyunsaturated fatty acids reduces postoperative atrial fibrillation. Therefore, their routine use in patients undergoing cardiac surgery is not recommended

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

Patient and Physician Predictors of FFR/iFR Utilization in ACS and SIHD

Background Despite guidelines supporting FFR/iFR to guide PCI, these modalities remain underutilized. We sought to characterize factors associated with FFR/iFR use in patients undergoing index PCI for an acute coronary syndrome (ACS) or stable ischemic heart disease (SIHD). Methods ICD-9/10 codes were used to identify patients undergoing PCI and receiving FFR/iFR for an ACS (n=1,042,896) or SIHD (n=255,213) in a Medicare claims database from Jan. 1, 2013-June 30, 2018. Patients with functional/anatomical testing were excluded (5d prior in ACS; 60d prior in SIHD). Individuals with FFR/iFR performed 1-60 days prior to PCI were also excluded to limit analysis to non-staged procedures. Results FFR/iFR was performed the same day as PCI in 5.9% and 11.5% of patients with an ACS and SIHD, respectively. FFR/iFR was less likely to be utilized in patients that were \u3e65 years, male, and in those with diabetes, chronic kidney disease or peripheral arterial disease. Of note, a substantial proportion of physicians were non-utilizers of FFR/iFR in ACS (23.9%) and SIHD (18.6%). Use of FFR/iFR was inversely correlated with years since medical school graduation, with the lowest rate observed in physicians \u3e=31 years since graduation (Table). Conclusion This analysis highlights the underutilization of FFR/iFR. Identification of patient- and physician-factors associated with lower rates of FFR/iFR can be helpful to target areas for improvement to increase implementation of this guideline-recommended intervention

Outcomes associated with familial versus nonfamilial atrial fibrillation:a matched nationwide cohort study

BACKGROUND: We examined all‐cause mortality and long‐term thromboembolic risk (ischemic stroke, transient ischemic attack, systemic thromboembolism) in patients with and without familial atrial fibrillation (AF). METHODS AND RESULTS: Using Danish nationwide registry data, we identified all patients diagnosed with AF (1995–2012) and divided them into those with familial AF (having a first‐degree family member with a prior AF admission) and those with nonfamilial AF. We paired those with and without familial AF according to age, year of AF diagnosis, and sex in a 1:1 match. Using cumulative incidence and multivariable Cox models, we examined the risk of long‐term outcomes. We identified 8658 AF patients (4329 matched pairs) with and without familial AF. The median age was 50 years (interquartile range 43–54 years), and 21.4% were women. Compared with nonfamilial AF patients, those with familial AF had slightly less comorbid illness but similar overall CHA (2) DS (2)‐VASc score (P=0.155). Median follow‐up was 3.4 years (interquartile range 1.5–6.5 years). Patients with familial AF had risk of death and thromboembolism similar to those with nonfamilial AF (adjusted hazard ratio 0.91 [95% CI 0.79–1.04] for death and 0.90 [95% CI 0.71–1.14] for thromboembolism). CONCLUSIONS: Although family history of AF is associated with increased likelihood for development of AF, once AF developed, long‐term risks of death and thromboembolic complications were similar in familial and nonfamilial AF patients

Multicenter, Randomized, Active Comparator-Controlled, Double-Blind, Double-Dummy, Parallel Group, Dose-Finding Phase 2 Study Comparing the Safety of the Oral FXIa Inhibitor Asundexian with Apixaban in Patients with Atrial Fibrillation

© 2022 Elsevier Ltd. All rights reserved. his is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1016/S0140-6736(22)00456-1Background Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. Methods In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. Findings Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14–1·68) for asundexian 20 mg (three events), 0·16 (0·01–0·99) for asundexian 50 mg (one event), and 0·33 (0·09–0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. Interpretation The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation.Peer reviewe

Outcomes After Cardioversion and Atrial Fibrillation Ablation in Patients Treated With Rivaroxaban and Warfarin in the ROCKET AF Trial

ObjectivesThis study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban.BackgroundThere are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors.MethodsWe compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial.ResultsOver a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups.ConclusionsDespite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation [ROCKET AF]; NCT00403767