The PREDIMED (Prevención con Dieta Mediterránea) randomized primary prevention trial showed that a Mediterranean diet enriched with either extravirgin olive oil or mixed nuts reduces the incidence of ...stroke, myocardial infarction, and cardiovascular mortality. We assessed the effect of these diets on the incidence of atrial fibrillation in the PREDIMED trial.
Participants were randomly assigned to 1 of 3 diets: Mediterranean diet supplemented with extravirgin olive oil, Mediterranean diet supplemented with mixed nuts, or advice to follow a low-fat diet (control group). Incident atrial fibrillation was adjudicated during follow-up by an events committee blinded to dietary group allocation. Among 6705 participants without prevalent atrial fibrillation at randomization, we observed 72 new cases of atrial fibrillation in the Mediterranean diet with extravirgin olive oil group, 82 in the Mediterranean diet with mixed nuts group, and 92 in the control group after median follow-up of 4.7 years. The Mediterranean diet with extravirgin olive oil significantly reduced the risk of atrial fibrillation (hazard ratio, 0.62; 95% confidence interval, 0.45-0.85 compared with the control group). No effect was found for the Mediterranean diet with nuts (hazard ratio, 0.89; 95% confidence interval, 0.65-1.20).
In the absence of proven interventions for the primary prevention of atrial fibrillation, this post hoc analysis of the PREDIMED trial suggests that extravirgin olive oil in the context of a Mediterranean dietary pattern may reduce the risk of atrial fibrillation.
http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.
The Incidence of Phrenic Nerve Injury
Introduction
The second‐generation cryoballoon (CB; Arctic Front Advance, Medtronic Inc., Minneapolis, MN, USA) has demonstrated greater procedural efficacy ...compared to the original CB. Whether increased efficacy translates into a higher incidence of phrenic nerve (PN) injury needs further evaluation.
Materials and Methods
In patients with drug‐refractory paroxysmal atrial fibrillation (AF) or short‐standing persistent AF, pulmonary vein isolation (PVI) was performed using the 28 mm second‐generation CB. During cryoenergy delivery along the septal PVs, continuous PN pacing was performed. The freeze cycle was aborted in case of weakening or loss of diaphragmatic contraction.
Results
A total of 115 patients (42 female, mean age 61 ± 11 years, mean LA‐diameter 43 ± 6 mm) with a history of paroxysmal AF (93/115 patients 81%) or short‐standing persistent AF (22/115 patients 19%) underwent CB‐based PVI. A total 445 of 448 (99%) PVs were isolated successfully. PN palsy (PNP) occurred in 4 of 115 (3.5%) patients, while applying cryoenergy to the right superior PV. Despite prompt interruption of the freezing cycle, PN function failed to recover during the periprocedural phase. PN recovery was observed as late as 10 months postablation.
Conclusions
Using the second‐generation 28 mm CB, PNP occurred in 4 of 115 (3.5%) patients. While 1 of 4 PNP recovered 10 months after ablation, long‐term outcome in the remaining 3 patients is currently unknown due to the rather short follow‐up period.
The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in ...clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex.
Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models.
Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio HR, 0.509 95% CI, 0.447-0.580; and HR, 0.541 95% CI, 0.487-0.601, respectively;
<0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 95% CI, 0.555-0.772; and HR, 0.649 95% CI, 0.552-0.762, respectively;
<0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 95% CI, 0.676-0.882; and HR, 0.881 95% CI, 0.784-0.989, respectively;
<0.05).
In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.
The utility of anticoagulants for ischemic stroke prophylaxis in elderly patients with chronic kidney disease (CKD) and atrial fibrillation remains uncertain. In this population-based retrospective ...cohort study, we determined the association of anticoagulant use with ischemic stroke or hemorrhage in elderly patients (66 years and older) with advanced chronic kidney disease (eGFR under 45 ml/min/1.73m2) and atrial fibrillation. We followed 6,544 patients with CKD and new onset atrial fibrillation, of whom 1,475 filled a prescription for an anticoagulant. We used propensity-score matched Cox proportional hazards and competing risk models to determine the time to first event of ischemic stroke, hemorrhage or mortality. After matching to examine exposure to anticoagulants, 1,417 matched pairs were identified. The crude rate of ischemic stroke and hemorrhage were 41.3 and 61.3 with anticoagulants and 34.4 and 34.3 without anticoagulants per 100 person-years, respectively. The hazard ratios of ischemic stroke, hemorrhage, and mortality for receipt of an anticoagulation prescription were 1.10 (95% confidence interval, 0.78–1.56), 1.42 (1.04–1.93), and 0.74 (0.62–0.88) as compared to non-receipt of anticoagulation. After accounting for the competing risk of death, the hazard ratios for ischemic stroke and hemorrhage were 1.12 (0.90–1.39) and 1.60 (1.31–1.97), respectively. The findings were consistent in a sensitivity analysis accounting for time varying anticoagulant exposure. Thus, in older patients with CKD and atrial fibrillation, receipt of an anticoagulant was not associated with a lower risk of ischemic stroke, but a higher risk of hemorrhage and a lower risk of mortality.
The risk-benefit ratio of left atrial appendage closure (LAAC) versus systemic therapy (warfarin) for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial ...fibrillation (NVAF) requires continued evaluation.
This study sought to assess composite data regarding left atrial appendage closure (LAAC) in 2 randomized trials compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in patients with nonvalvular AF.
Our meta-analysis included 2,406 patients with 5,931 patient-years (PY) of follow-up from the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device In Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trials, and their respective registries (Continued Access to PROTECT AF registry and Continued Access to PREVAIL registry).
With mean follow-up of 2.69 years, patients receiving LAAC with the Watchman device had significantly fewer hemorrhagic strokes (0.15 vs. 0.96 events/100 patient-years PY; hazard ratio HR: 0.22; p = 0.004), cardiovascular/unexplained death (1.1 vs. 2.3 events/100 PY; HR: 0.48; p = 0.006), and nonprocedural bleeding (6.0% vs. 11.3%; HR: 0.51; p = 0.006) compared with warfarin. All-cause stroke or systemic embolism was similar between both strategies (1.75 vs. 1.87 events/100 PY; HR: 1.02; 95% CI: 0.62 to 1.7; p = 0.94). There were more ischemic strokes in the device group (1.6 vs. 0.9 and 0.2 vs. 1.0 events/100 PY; HR: 1.95 and 0.22, respectively; p = 0.05 and 0.004, respectively). Both trials and registries identified similar event rates and consistent device effect in multiple subsets.
In patients with NVAF at increased risk for stroke or bleeding who are candidates for chronic anticoagulation, LAAC resulted in improved rates of hemorrhagic stroke, cardiovascular/unexplained death, and nonprocedural bleeding compared to warfarin.
The purpose of this study was to compare the relative risk of major bleeding with left atrial appendage (LAA) closure compared with long-term warfarin therapy.
LAA closure is an alternative approach ...to chronic oral anticoagulation for the prevention of thromboembolism in patients with atrial fibrillation (AF).
We conducted a pooled, patient-level analysis of the 2 randomized clinical trials that compared WATCHMAN (Boston Scientific, Natick, Massachusetts) LAA closure with long-term warfarin therapy in AF.
A total of 1,114 patients were included, with a median follow-up of 3.1 years. The overall rate of major bleeding from randomization to the end of follow-up was similar between treatment groups (3.5 events vs. 3.6 events per 100 patient-years; rate ratio RR: 0.96; 95% confidence interval CI: 0.66 to 1.40; p = 0.84). LAA closure significantly reduced bleeding >7 days post-randomization (1.8 events vs. 3.6 events per 100 patient-years; RR: 0.49; 95% CI: 0.32 to 0.75; p = 0.001), with the difference emerging 6 months after randomization (1.0 events vs. 3.5 events per 100 patient-years; RR: 0.28; 95% CI: 0.16 to 0.49; p < 0.001), when patients assigned to LAA closure were able to discontinue adjunctive oral anticoagulation and antiplatelet therapy. The reduction in bleeding with LAA closure was directionally consistent across all patient subgroups.
There was no difference in the overall rate of major bleeding in patients assigned to LAA closure compared with extended warfarin therapy over 3 years of follow-up. However, LAA closure significantly reduced bleeding beyond the procedural period, particularly once adjunctive pharmacotherapy was discontinued. The favorable effect of LAA closure on long-term bleeding should be considered when selecting a stroke prevention strategy for patients with nonvalvular AF. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy PREVAIL; NCT01182441).
Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to ...dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR).
Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e', medial E/e', tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (>MDD) by ≥2/4. Annualized changes in DD indices were determined.
New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6-5.8) years, DD progressed two-four-fold more rapidly in those with new-onset AF (P < .001 for all). The risk for incident DD was increased in new-onset AF hazard ratio (95% confidence interval) 2.69 (2.19-3.32) for SDD and 1.73 (1.49-2.02) for ≥MDD.
Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.
ObjectiveThere has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation ...(AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics.MethodsMEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF.ResultsOne hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing.ConclusionsOur analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF.PROSPERO registration numberCRD42020219844.
Previous studies on the cost-effectiveness of screening for atrial fibrillation (AF) are based on assumptions of long-term clinical effects. The STROKESTOP study, which randomised 27 975 persons aged ...75/76 years into a screening invitation group and a control group, has a median follow-up time of 6.9 years. The aim of this study was to estimate the cost-effectiveness of population-based screening for AF using clinical outcomes.
The analysis is based on a Markov cohort model. The prevalence of AF, the use of oral anticoagulation, clinical event data, and all-cause mortality were taken from the STROKESTOP study. The cost for clinical events, age-specific utilities, utility decrement due to stroke, and stroke death was taken from the literature. Uncertainty in the model was considered in a probabilistic sensitivity analysis. Per 1000 individuals invited to the screening, there were 77 gained life years and 65 gained quality-adjusted life years. The incremental cost was €1.77 million lower in the screening invitation group. Gained quality-adjusted life years to a lower cost means that the screening strategy was dominant. The result from 10 000 Monte Carlo simulations showed that the AF screening strategy was cost-effective in 99.2% and cost-saving in 92.7% of the simulations. In the base-case scenario, screening of 1000 individuals resulted in 10.6 95% confidence interval (CI): -22.5 to 1.4 fewer strokes (8.4 ischaemic and 2.2 haemorrhagic strokes), 1.0 (95% CI: -1.9 to 4.1) more cases of systemic embolism, and 2.9 (95% CI: -18.2 to 13.1) fewer bleedings associated with hospitalization.
Based on the STROKESTOP study, this analysis shows that a broad AF screening strategy in an elderly population is cost-effective. Efforts should be made to increase screening participation.
Abstract
Aims
To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin.
Methods and results
We ...conducted a real-world nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19 414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk aHR = 0.84, 95% confidence interval (CI) = 0.77–0.93; P < 0.001. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78–0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72–0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52–0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results.
Conclusion
Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality.
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