Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation.

BACKGROUND: Biomarkers reflecting brain injury are not routinely used in risk assessment of stroke in atrial fibrillation (AF). Neurofilament light chain (NFL) is a novel biomarker released into blood after cerebral insults. We investigated the association between plasma concentrations of NFL, other biomarkers, and risk of stroke and death in patients with AF not receiving oral anticoagulation. METHODS: For this observational study, baseline plasma samples were available from 3077 patients with AF randomized to aspirin in ACTIVE A (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events; 2003 to 2008) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; 2007 to 2009). Median follow-up was 1.5 years. NFL was analyzed with a Single Molecule Array (Simoa). Associations with outcomes (total stroke or systemic embolism, ischemic stroke, cardiovascular death, and all-cause death) were explored with Cox regression models. RESULTS: In the combined cohort, the median NFL level was 16.9 ng/L (interquartile range, 11.1-26.5 ng/L), the median age was 71 years, 58% were men, and 13% had a history of previous stroke. NFL was associated with older age, higher creatinine, lower body mass index, previous stroke, female sex, and diabetes but not cardiac rhythm. Higher NFL was associated with a higher risk of stroke or systemic embolism (n=206) independently of clinical characteristics (hazard ratio, 1.27 [95% CI, 1.10-1.46] per doubling of NFL) and other biomarkers (hazard ratio, 1.18 [95% CI, 1.01-1.37]) and including in patients without previous stroke (hazard ratio, 1.23 [95% CI, 1.02-1.48]). NFL was also independently associated with cardiovascular (n=219) and all-cause (n=311) death. The C index for stroke using only NFL was 0.642, on par with the currently used clinical risk scores. Addition of information on NFL improved discrimination in a model also including clinical information, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and high-sensitivity cardiac troponin T, yielding a C index of 0.727. CONCLUSIONS: NFL reflects overt and covert episodes of cerebral ischemia and improves risk assessment of stroke and death in patients with AF without oral anticoagulation, including in patients without previous stroke. The combination of NFL with information on age, history of stroke, and other biomarkers should be explored as a future avenue for stroke risk assessments in patients with AF.

Direct Oral Anticoagulants for Stroke Prevention in Patients With Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials.

BACKGROUND: Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear. METHODS: We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212). RESULTS: From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50-0.92]; high-quality evidence). The results from the 2 trials were consistent (I2 statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73-0.99]; I2=0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76-1.17]; I2=0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96-1.21]; I2=0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05-2.50]; I²=61%; high-quality evidence). CONCLUSIONS: The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding.

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

BACKGROUND AND AIMS: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. METHODS: MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. RESULTS: Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. CONCLUSIONS: Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

In DVT, oral DTIs and factor Xa inhibitors reduce major bleeding but not recurrent VTE vs. conventional anticoagulants.

SOURCE CITATION: Wang X, Ma Y, Hui X, et al. Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis. Cochrane Database Syst Rev. 2023;4:CD010956. 37058421.

Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation.

AIMS: Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC). METHODS AND RESULTS: BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death. CONCLUSION: The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF. ONE-SENTENCE SUMMARY: In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation.

Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation.

AIMS: The prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation. METHODS AND RESULTS: Individual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%-8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%-14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%-7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%-8.9%). CONCLUSION: Patients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex.

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data. METHODS: We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex. RESULTS: A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin. CONCLUSIONS: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.

Individual net clinical outcome with oral anticoagulation in atrial fibrillation using the ABC-AF risk scores.

BACKGROUND: Decisions on stroke prevention strategies in patients with atrial fibrillation (AF) depend on the perceived risks of stroke and bleeding with different antithrombotic treatment strategies. The study objectives were to evaluate net clinical outcome with oral anticoagulation (OAC) for the individual patient with AF and to identify clinically relevant thresholds for OAC treatment. METHODS: Patients with AF receiving OAC treatment in the randomized ARISTOTLE and RE-LY trials, with available biomarkers for calculation of ABC-AF scores at baseline, were included (n = 23,121). Observed 1-year risk on OAC was compared with predicted 1-year risk if the same patients would not have received OAC using the ABC-AF scores calibrated for aspirin. Net clinical outcome was defined as the sum of stroke and major bleeding risks. RESULTS: The ratio between the 1-year incidence of major bleeding and stroke/systemic embolism events ranged from 1.4 to 10.6 according to different ABC-AF risk profiles. Net clinical outcome analyses showed that in patients with an ABC-AF-stroke risk >1% per year on OAC (>3% without OAC), treatment with OAC consistently provides larger net clinical benefit than no-OAC treatment. In patients with an ABC-AF-stroke risk <1.0% per year on OAC (<3% without OAC) an individualized balancing of risks regarding OAC or no-OAC treatment is needed. CONCLUSIONS: In patients with AF, the ABC-AF risk scores allow an individual and continuous estimate of the balance between benefits and risks with OAC treatment. This precision medicine tool therefore seems useful as decision support and visualizes the net clinical benefit or harm with OAC treatment (http://www.abc-score.com/abcaf/). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00412984 (ARISTOTLE) and NCT00262600 (RE-LY).

Plasma angiopoietin-2 and its association with heart failure in patients with atrial fibrillation.

AIMS: Several biomarkers are associated with clinical outcomes in patients with atrial fibrillation (AF), but a causal relationship has not been established. This study aimed to evaluate angiopoietin-2, a novel candidate biomarker of endothelial inflammation and vascular remodelling, in patients with AF. METHODS AND RESULTS: Angiopoietin-2 was measured in plasma obtained from patients with AF treated with aspirin monotherapy (exploration cohort, n = 2987) or with oral anticoagulation (validation cohort, n = 13 079). Regression models were built to assess the associations between angiopoietin-2, clinical characteristics, and outcomes. In both cohorts, plasma angiopoietin-2 was independently associated with AF on the baseline electrocardiogram and persistent/permanent AF, age, history of heart failure, female sex, tobacco use/smoking, body mass index, renal dysfunction, diabetes, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Angiopoietin-2 was independently associated with subsequent hospitalization for heart failure after adjusting for age, creatinine, and clinical characteristics in the exploration cohort [c-index 0.79, 95% confidence interval (CI) 0.75-0.82; third vs. first quartile, hazard ratio (HR) 1.74, 95% CI 1.26-2.41] and in the validation cohort (c-index 0.76, 95% CI 0.74-0.78; HR 1.58, 95% CI 1.37-1.82). In both cohorts, the association persisted when also adjusting for NT-proBNP (P ≤ 0.001). In full multivariable models also adjusted for NT-proBNP, angiopoietin-2 did not show statistically significant associations with ischaemic stroke, cardiovascular and all-cause death, or major bleeding that were consistent across the two cohorts. CONCLUSIONS: In patients with AF, plasma levels of angiopoietin-2 were independently associated with subsequent hospitalization for heart failure and provided incremental prognostic value to clinical risk factors and NT-proBNP.

Techniques improving electrical cardioversion success for patients with atrial fibrillation: a systematic review and meta-analysis.

AIMS: Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients. METHODS AND RESULTS: We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29-2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04-1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33-1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21-3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06-1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97-1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96-1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91-1.34; cumulative: four trials, RR 0.98, 95% CI 0.89-1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92-1.07). CONCLUSIONS: Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study.

Biomarker-Based Risk Prediction With the ABC-AF Scores in Patients With Atrial Fibrillation Not Receiving Oral Anticoagulation.

BACKGROUND: The novel ABC (Age, Biomarkers, Clinical History) scores outperform traditional risk scores for stroke, major bleeding, and death in patients with atrial fibrillation (AF) receiving oral anticoagulation. To refine their utility, the ABC-AF scores needed to be validated in patients not receiving oral anticoagulation. METHODS: We measured plasma levels of the ABC biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-T, and growth-differentiation factor 15) to apply the previously developed ABC-AF scores in patients with AF receiving aspirin (n=3195) or aspirin and clopidogrel (n=1110) in 2 large clinical trials. Calibration was assessed by comparing estimated with observed 1-year risks. Cox regression models were used for recalibration. Discrimination was evaluated separately for the aspirin-only and the overall cohort (n=4305). RESULTS: The ABC-AF-stroke score yielded a c-index of 0.70 (95% CI, 0.67-0.73) in both cohorts. The ABC-AF-bleeding score had a c-index of 0.76 (95% CI, 0.71-0.81) in the aspirin-only cohort and 0.73 (95% CI, 0.69-0.77) overall. Both scores were superior to risk scores recommended by current guidelines. The ABC-AF-death score yielded a c-index of 0.78 (95% CI, 0.76-0.80) overall. Calibrated in patients receiving oral anticoagulation, the ABC-AF-stroke score underestimated and the ABC-AF-bleeding score overestimated the risk of events in both cohorts. These scores were recalibrated for prediction of absolute event rates in the absence of oral anticoagulation. CONCLUSIONS: The biomarker-based ABC-AF scores showed better discrimination than traditional risk scores and were recalibrated for precise risk estimation in patients not receiving oral anticoagulation. They can now provide improved decision support on treatment of an individual patient with AF.

Estimated incidence of previously undetected atrial fibrillation on a 14-day continuous electrocardiographic monitor and associated risk of stroke.

AIMS: There is uncertainty about whether and how to perform screening for atrial fibrillation (AF). To estimate the incidence of previously undetected AF that would be captured using a continuous 14-day ECG monitor and the associated risk of stroke. METHODS AND RESULTS: We analysed data from a cohort of patients >65 years old with hypertension and a pacemaker, but without known AF. For each participant, we simulated 1000 ECG monitors by randomly selecting 14-day windows in the 6 months following enrolment and calculated the average AF burden (total time in AF). We used Cox proportional hazards models adjusted for CHA2DS2-VASc score to estimate the risk of subsequent ischaemic stroke or systemic embolism (SSE) associated with burdens of AF > and <6 min. Among 2470 participants, the median CHA2DS2-VASc score was 4.0, and 44 patients experienced SSE after 6 months following enrolment. The proportion of participants with an AF burden >6 min was 3.10% (95% CI 2.53-3.72). This was consistent across strata of age and CHA2DS2-VASc scores. Over a mean follow-up of 2.4 years, the rate of SSE among patients with <6 min of AF was 0.70%/year, compared to 2.18%/year (adjusted HR 3.02; 95% CI 1.39-6.56) in those with >6 min of AF. CONCLUSIONS: Approximately 3% of individuals aged >65 years with hypertension may have more than 6 min of AF detected by a 14-day ECG monitor. This is associated with a stroke risk of over 2% per year. Whether oral anticoagulation will reduce stroke in these patients is unknown.

Oral anticoagulation for patients with atrial fibrillation in the ED: RE-LY AF registry analysis.

Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF). We sought to determine predictors of OAC initiation in AF patients presenting to the emergency department (ED). Secondary analysis of the RE-LY AF registry which enrolled individuals from 47 countries between 2007 and 2011 who presented to an ED with AF and followed them for 1 year. A total of 4149 patients with AF as their primary diagnosis who were not already taking OAC and had a CHA2DS2-VASc ≥ 1 for men or ≥ 2 for women were included in this analysis. Of these individuals, 26.8% were started on OAC (99.2% vitamin K antagonists) in the ED and 29.8% were using OAC one year later. Factors associated with initiating OAC in the ED included: specialist consultation (relative risk [RR] 1.84, 95%CI 1.44-2.36), rheumatic heart disease (RR 1.60, 95%CI 1.29-1.99), persistence of AF at ED discharge (RR 1.33, 95%CI 1.18-1.50), diabetes mellitus (RR 1.32, 95%CI 1.19-1.47), and hospital admission (RR 1.30, 95%CI 1.14-1.47). Heart failure (RR 0.83, 95%CI 0.74-0.94), antiplatelet agents (RR 0.77, 95%CI 0.69-0.84), and dementia (RR 0.61, 95%CI 0.40-0.94) were inversely associated with OAC initiation. Patients taking OAC when they left the ED were more likely using OAC at 1-year (RR 2.81, 95%CI 2.55-3.09) and had lower rates of death (RR 0.55, 95%CI 0.38-0.79) and stroke (RR 0.59, 95%CI 0.37-0.96). In patients with AF presenting to the ED, prompt initiation of OAC and specialist involvement are associated with a greater use of OAC 1 year later and may result in improved clinical outcomes.

Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. METHODS: We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration. RESULTS: From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs. CONCLUSION: Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.

Incidence and recurrence of new-onset atrial fibrillation detected during hospitalization for non-cardiac surgery: a systematic review and meta-analysis.

PURPOSE: This systematic review aimed to summarize reports of the incidence and long-term recurrence of new-onset atrial fibrillation (AF) associated with non-cardiac surgery. SOURCES: We searched CENTRAL, MEDLINE and EMBASE from inception to November 2019. We included studies that reported on the incidence of new-onset perioperative AF during hospitalization for non-cardiac surgery and/or AF recurrence in such patients following discharge. Reviewers screened articles and abstracted data independently and in duplicate. We assessed study quality by appraising methodology for collecting AF history, incident AF during hospitalization, and AF recurrence after discharge. PRINCIPAL FINDINGS: From 39,233 citations screened, 346 studies that enrolled a total of 5,829,758 patients met eligibility criteria. Only 27 studies used prospective, continuous inpatient electrocardiographic (ECG) monitoring to detect incident AF. Overall, the incidence of postoperative AF during hospitalization ranged from 0.004 to 50.3%, with a median [interquartile range] of 8.7 [3.8-15.0]%. Atrial fibrillation incidence varied with type of surgery. Prospective studies using continuous ECG monitoring reported significantly higher incidences of AF than those that did not (13.9% vs 1.9%, respectively; P < 0.001). A total of 13 studies (25,726 patients) with follow-up up to 5.4 years reported on AF recurrence following hospital discharge; only one study used a prospective systematic monitoring protocol. Recurrence rates ranged from 0 to 37.3%. CONCLUSIONS: Rates of AF incidence first detected following non-cardiac surgery and long-term AF recurrence vary markedly. Differences in the intensity of ECG monitoring and type of surgery may account for this variation. TRIAL REGISTRATION: PROSPERO (CRD42017068055); registered 1 September 2017.

RéSUMé: OBJECTIF: Cette revue systématique visait à résumer les comptes rendus sur l'incidence et la récurrence à long terme de la fibrillation auriculaire (FA) de novo associée à une chirurgie non cardiaque. SOURCES: Nous avons effectué des recherches dans les bases de données CENTRAL, MEDLINE et EMBASE de leur création à novembre 2019. Nous avons inclus les études ayant examiné l'incidence de nouvelle FA périopératoire pendant l'hospitalisation pour une chirurgie non cardiaque et/ou la récurrence de la FA chez de tels patients après leur congé. Les chercheurs ont passé en revue les articles et les données extraites de manière indépendante et en double. Nous avons estimé la qualité des études en évaluant la méthodologie de collecte des antécédents de FA, de l'incident de FA pendant l'hospitalisation et de la récurrence de FA après le congé. CONSTATATIONS PRINCIPALES: Sur les 39 233 citations examinées, 346 études portant sur un total de 5 829 758 patients ont répondu à nos critères d'admissibilité. Seulement 27 études ont utilisé un monitorage électrocardiographique (ECG) continu prospectif et des patients hospitalisés pour détecter les incidents de FA. Dans l'ensemble, l'incidence de FA postopératoire pendant l'hospitalisation allait de 0,004 à 50,3 %, avec une médiane [écart interquartile] de 8,7 [3,8-15,0] %. L'incidence de fibrillation auriculaire variait en fonction du type de chirurgie. Des études prospectives utilisant un monitorage continu par ECG ont fait état d'incidences significativement plus élevées de FA que celles sans monitorage continu (13,9 % vs 1,9 %, respectivement; P < 0,001). Au total, 13 études (25 726 patients) avec un suivi allant jusqu'à 5,4 ans ont rapporté leurs données sur la récurrence de FA après le congé de l'hôpital; seule une étude a utilisé un protocole de monitorage prospectif systématique. Les taux de récurrence allaient de 0 à 37,3 %. CONCLUSION: Les taux d'incidence de nouvelle FA détectés après une chirurgie non cardiaque et la récurrence à long terme de FA varient considérablement. Les différences du degré de monitorage par ECG et le type de chirurgie pourraient expliquer cette variation. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42017068055); enregistrée le 1er septembre 2017.

Thromboembolic events around the time of cardioversion for atrial fibrillation in patients receiving antiplatelet treatment in the ACTIVE trials.

AIMS: It is unknown whether cardioversion of atrial fibrillation causes thromboembolic events or is a risk marker. To assess causality, we examined the temporal pattern of thromboembolism in patients having cardioversion. METHODS AND RESULTS: We studied patients randomized to aspirin or aspirin plus clopidogrel in the ACTIVE trials, comparing the thromboembolic rate in the peri-cardioversion period (30 days before until 30 days after) to the rate during follow-up, remote from cardioversion. Among 962 patients, the 30-day thromboembolic rate remote from cardioversion was 0.16%; while it was 0.73% in the peri-cardioversion period [hazard ratio (HR) 4.1, 95% confidence interval (CI) 2.1-7.9]. The 30-day thromboembolic rates in the periods immediately before and after cardioversion were 0.47% and 0.96%, respectively (HR 2.2, 95% CI 0.7-7.1). Heart failure (HF) hospitalization increased in the peri-cardioversion period (HR 11.5, 95% CI 6.8-19.4). Compared to baseline, the thromboembolic rate in the 30 days following cardioversion was increased both in patients who received oral anticoagulation or a transoesophageal echocardiogram prior to cardioversion (HR 7.9, 95% CI 2.8-22.4) and in those who did not (HR 4.8, 95% CI 1.6-14.9) (interaction P = 0.2); the risk was also increased with successful (HR 4.5; 95% CI 2.0-10.5) and unsuccessful (HR 10.2; 95% CI 2.3-44.9) cardioversion. CONCLUSIONS: Thromboembolic risk increased in the 30 days before cardioversion and persisted until 30 days post-cardioversion, in a pattern similar to HF hospitalization. These data suggest that the increased thromboembolic risk around the time of cardioversion may not be entirely causal, but confounded by the overall clinical deterioration of patients requiring cardioversion.

Clinical outcomes after implantation of quadripolar compared to bipolar left ventricular leads in patients undergoing cardiac resynchronization therapy: a systematic review and meta-analysis.

AIMS: Some retrospective and prospective studies in heart failure patients with indication for cardiac resynchronization therapy (CRT) suggest better clinical outcomes for quadripolar (QP) left ventricular (LV) leads over bipolar (BP) leads. Although, lead failure remains an important safety concern, when using these more complex, novel electrodes. To evaluate safety and efficacy outcomes for QP vs. BP LV leads in patients receiving CRT. METHODS AND RESULTS: We performed a comprehensive literature search through 2018 in PubMed, Cochrane Library, and Google Scholar databases to identify studies comparing patients with QP and BP LV CRT leads. A total of 12 studies were selected for analysis comprising 31 403 patients (QP lead: 22 429 patients; BP lead: 8974 patients). Eight studies examined the effects of CRT on survival. In these studies, use of QP electrodes was associated with significantly better survival compared to patients with BP LV leads (OR 0.61, 95% CI 0.50-0.76; P < 0.01). Clinical improval measured in New York Heart Association functional class (OR 0.59, 95% CI 0.34-1.01; P = 0.05) and hospitalization rates (OR 0.67, 95% CI 0.55-0.83; P < 0.01) were also improved in patients receiving QP leads. Lead malfunctions defined as LV lead failure resulting in lead deactivation (OR 0.57, 95% CI 0.34-0.98; P = 0.04) or LV lead dislodgement requiring LV lead replacement/repositioning (OR 0.48; 95% CI 0.31-0.75; P < 0.01) were more often encountered among patients with BP leads compared to patients with QP leads. CONCLUSION: Our meta-analysis suggests distinct benefits of QP over BP electrodes in patients undergoing CRT.

Cephalic vs. subclavian lead implantation in cardiac implantable electronic devices: a systematic review and meta-analysis.

AIMS: Cephalic vein cutdown (CVC) and subclavian puncture (SP) are widely used techniques for lead insertion of cardiac implantable electronic devices (CIEDs). Whether one technique is superior to the other, is still being debated. The purpose of this study was to compare CVC vs. SP for lead implantation in CIEDs with respect to the incidence of pneumothorax, lead failure, and bleeding. METHODS AND RESULTS: We performed a systematic search of the pertinent literature on lead implantation in CIEDs via PubMed and Cochrane databases published over the last 25 years. Standard meta-analytic methods were applied to compare incidences of outcomes of interest. Sensitivity analysis was conducted to determine the impact of each study on the overall effect size. Risk of publication bias was assessed. A total of 20 studies were included in the analysis. These studies comprised more than 30 000 patients with more than 50 000 leads implanted via CVC or SP. The incidence of pneumothorax was lower with the CVC technique (n = 29/15 065, 0.19% vs. n = 205/15 824, 1.30%) [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.10-0.42, P < 0.001]. With respect to overall lead failure, CVC was associated with better outcomes as compared to SP (n = 10/2002, 0.50% vs. n = 40/2080, 1.92%) (OR 0.25, 95% CI 0.13-0.51, P < 0.001). There was no significant difference in bleeding events (n = 25/811, 3.08% vs. n = 20/2136, 0.94%) (OR 1.69, 95% CI 0.37-7.79, P = 0.50). CONCLUSION: This comprehensive meta-analysis demonstrates lower risk for pneumothorax and lead failure associated with CVC as compared to SP. Cephalic vein cutdown should constitute the preferred venous access.