Usefulness of Long-Term Anticoagulation After Catheter Ablation of Atrial Fibrillation.

Although atrial fibrillation (AF) is strongly associated with stroke, previous studies have shown suboptimal use of anticoagulation (AC). In particular, there is a lack of data on the long-term use of AC after AF catheter ablation. We followed up patients 1 to 5 years out from catheter ablation at the Johns Hopkins Hospital (JHH) to assess their long-term use of AC. We sent a survey to patients from the JHH AF database who underwent an AF catheter ablation between 01/01/2014 and 03/31/2018. Patients were asked whether they were still on AC, if they thought the ablation was successful in controlling AF symptoms and whether they had follow-up rhythm monitoring. Replies were compared with risk scores and demographic data from the electronic medical record. We sent the survey to 628 patients in the database meeting our inclusion criteria, and we received 289 responses. The average age of patients was 67 ± 10 with a median CHA2DS2-VASc of 2 and a median follow-up of 3.6 years. Overall, 81.6% of patients with a CHA2DS2-VASc >2 reported taking AC. Use of AC was positively correlated with a higher CHA2DS2-VASc score (p = 0.012) and older age (p = 0.028), but negatively correlated with a successful ablation (p = 0.040). The most common reason (50.0%) for not being on AC was that doctors were recommending stopping it after a successful ablation. In general, higher risk patients (older, higher CHA2DS2-VASC score) were more likely to remain on AC. However, patients who self-reported a successful ablation were less likely to remain on AC. There may be many patients who can tolerate AC, but are recommended to stop due to a successful ablation. It is still debated how successful AF ablation affects stroke risk. In conclusion, there is considerable variation in the long-term management of AC after an ablation, but for the present, it seems prudent to continue AC based on stroke risk scores until more definite data are available.

Appropriateness of Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation: Insights From the Veterans Health Administration.

BACKGROUND: Direct oral anticoagulants (DOACs) have strict dosing guidelines, but recent studies indicate that inappropriate dosing is common, particularly in chronic kidney disease (CKD), for which it has been reported to be as high as 43%. Since 2011, the Veterans Health Administration (VA) has implemented anticoagulation management programs for DOACs, generally led by pharmacists, which has previously been shown to improve medication adherence. OBJECTIVE: We investigated the prevalence of overdosing and underdosing of DOACs in the VA. METHODS: Using data from the TREAT-AF cohort study (The Retrospective Evaluation and Assessment of Therapies in AF), we identified VA patients with newly diagnosed atrial fibrillation (AF) and receipt of a DOAC between 2003 and 2015. We classified dosing as correct, overdosed, or underdosed based on the Food and Drug Administration-approved dosing criteria. RESULTS: Of 230 762 patients, 5060 received dabigatran (77.3%) or rivaroxaban (22.7%) within 90 days of AF diagnosis (age 69 [10[ years; CHA2DS2-VASc 1.6 [1.4]), of which 1312 (25.9%) had CKD based on estimated glomerular filtration rate <60. Overall, 93.6% of patients, 83.2% with CKD, received appropriate DOAC dosing. Incorrect dosing increased with worsening renal function. CONCLUSION: Compared to recent studies of commercial payers and health-care systems, incorrect dosing of DOACs is less common across the VA. Pharmacist-led DOAC management or similar anticoagulation management interventions may reduce the risk of incorrect dosing across health-care systems.

Site Variation and Outcomes for Antithrombotic Therapy in Atrial Fibrillation Patients After Percutaneous Coronary Intervention.

BACKGROUND: Patients with atrial fibrillation (AF) treated with percutaneous coronary intervention (PCI) require multiple antithrombotic therapies. The optimal strategy is debated suggesting increased treatment variation. This study sought to characterize site-level variation in antithrombotic therapies in AF patients after PCI and determine the association with outcomes. METHODS: Using the retrospective TREAT-AF study (The Retrospective Evaluation and Assessment of Therapies in AF) from the Veterans Health Administration, patients with newly diagnosed, nonvalvular AF between 2004 and 2015 followed by a PCI with a P2Y12-antagonist prescription were identified. Patients were grouped according to the therapy dispensed 7 days before until 30 days after the PCI: oral anticoagulation plus platelet inhibition (OAC+PI) or platelet inhibition only. A combined outcome of death, myocardial infarction, stroke, or major bleeding was assessed 1 year after PCI and Cox regression was performed to estimate hazard ratios. RESULTS: Of 230 762 patients with newly diagnosed AF, 4042 (1.8%) underwent PCI and received a P2Y12-antagonist during the observation period (age, 67±9 years; CHA2DS2-VASc, 2.7±1.7; HAS-BLED, 2.6±1.2). Among these, 47% were prescribed OAC+PI, and 53% platelet inhibition only 7 days before until 30 days after the PCI. Across 63 sites, the use of OAC+PI ranged from 19% to 66%. Prescription of OAC+PI was independently associated with a reduction in the combined outcome of death, myocardial infarction, stroke, or major bleeding compared with platelet inhibition only (adjusted hazard ratio, 0.85; 95% CI, 0.73-0.99; P=0.033). CONCLUSIONS: In patients with established AF undergoing PCI, the use of OAC+PI varied substantially across sites in the 30 days post-PCI. Anticoagulation appeared to be underutilized but was associated with improved outcomes. Strategies to promote OAC+PI and minimize site variation may be useful, particularly in light of recent randomized trials.

Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation.

BACKGROUND: Localized drivers are proposed mechanisms for persistent atrial fibrillation (AF) from optical mapping of human atria and clinical studies of AF, yet are controversial because drivers fluctuate and ablating them may not terminate AF. We used wavefront field mapping to test the hypothesis that AF drivers, if concurrent, may interact to produce fluctuating areas of control to explain their appearance/disappearance and acute impact of ablation. METHODS: We recruited 54 patients from an international registry in whom persistent AF terminated by targeted ablation. Unipolar AF electrograms were analyzed from 64-pole baskets to reconstruct activation times, map propagation vectors each 20 ms, and create nonproprietary phase maps. RESULTS: Each patient (63.6±8.5 years, 29.6% women) showed 4.0±2.1 spatially anchored rotational or focal sites in AF in 3 patterns. First, a single (type I; n=7) or, second, paired chiral-antichiral (type II; n=5) rotational drivers controlled most of the atrial area. Ablation of 1 to 2 large drivers terminated all cases of types I or II AF. Third, interaction of 3 to 5 drivers (type III; n=42) with changing areas of control. Targeted ablation at driver centers terminated AF and required more ablation in types III versus I (P=0.02 in left atrium). CONCLUSIONS: Wavefront field mapping of persistent AF reveals a pathophysiologic network of a small number of spatially anchored rotational and focal sites, which interact, fluctuate, and control varying areas. Future work should define whether AF drivers that control larger atrial areas are attractive targets for ablation.

Secular trends in success rate of catheter ablation for atrial fibrillation: The SMASH-AF cohort.

BACKGROUND: Approaches, tools, and technologies for atrial fibrillation (AF) ablation have evolved significantly since its inception. We sought to characterize secular trends in AF ablation success rates. METHODS: We performed a systematic review and meta-analysis of AF ablation from January 1, 1990, to August 1, 2016, searching PubMed, Scopus, and Cochrane databases. Major exclusion criteria were insufficient outcome reporting and ablation strategies that were not prespecified and uniform. We stratified treatment arms by AF type (paroxysmal AF; nonparoxysmal AF) and analyzed single-procedure outcomes. Multivariate meta-regressions analyzed effects of study, patient, and procedure characteristics on success rate trends. Registered in PROSPERO (CRD42016036549). RESULTS: A total of 180 trials and observational studies with 28,118 patients met inclusion. For paroxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 73.1% in 2003 to 77.1% in 2016, increasing by 0.9%/year (95% CI 0.4%-1.4%; P = .001; I2 = 90%). After controlling for study design and patient demographics, rate of improvement in success rate summary estimate increased (1.6%/year; 95% CI 0.9%-2.2%; P = .001; I2 = 87%). For nonparoxysmal AF ablation studies, unadjusted success rate summary estimates ranged from 70.0% in 2010 to 64.3% in 2016 (1.1%/year; 95% CI -1.3% to 3.5%; P = .37; I2 = 85%), with no improvement in multivariate analyses. CONCLUSIONS: Despite substantial research investment and health care expenditure, improvements in AF ablation success rates have been incremental. Meaningful improvements may require major paradigm or technology changes, and evaluation of clinical outcomes such as mortality and quality of life may prove to be important going forward.

Efficacy of Ablation Lesion Sets in Addition to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation: Findings From the SMASH - AF Meta-Analysis Study Cohort.

Background The objective was to explore the efficacy of ablation lesion sets in addition to pulmonary vein isolation ( PVI ) for paroxysmal atrial fibrillation. The optimal strategy for catheter ablation of paroxysmal atrial fibrillation is debated. Methods and Results The SMASH-AF (Systematic Review and Meta-analysis of Ablation Strategy Heterogeneity in Atrial Fibrillation) study cohort includes trials and observational studies identified in PubMed, Scopus, and Cochrane databases from January 1 1990, to August 1, 2016. We included studies reporting single procedure paroxysmal atrial fibrillation ablation success rates. Exclusion criteria included insufficient reporting of outcomes, ablation strategies that were not prespecified and uniform, and a sample size of fewer than 40 patients. We analyzed lesion sets performed in addition to PVI ( PVI plus) using multivariable random-effects meta-regression to control for patient, study, and procedure characteristics. The analysis included 145 total studies with 23 263 patients ( PVI- only cohort: 115 studies, 148 treatment arms, 16 500 patients; PVI plus cohort: 39 studies; 46 treatment arms, 6763 patients). PVI plus studies, as compared with PVI -only studies, included younger patients (56.7 years versus 58.8 years, P=0.001), fewer women (27.2% versus 32.0% women, P=0.002), and were more methodologically rigorous with longer follow-up (29.5 versus 17.1 months, P 0.004) and more randomization (19.4% versus 11.8%, P<0.001). In multivariable meta-regression, PVI plus studies were associated with improved success (7.6% absolute improvement [95% CI, 2.6-12.5%]; P<0.01, I2=88%), specifically superior vena cava isolation (4 studies, 4 treatment arms, 1392 patients; 15.1% absolute improvement [95% CI, 2.3-27.9%]; P 0.02, I2=87%). However, residual heterogeneity was large. Conclusions Across the paroxysmal atrial fibrillation ablation literature, PVI plus ablation strategies were associated with incremental improvements in success rate. However, large residual heterogeneity complicates evidence synthesis.

Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression.

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (P < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR.Significance: HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. Cancer Res; 78(14); 3769-82. ©2018 AACR.

Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation.

OBJECTIVE: To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI). INTRODUCTION: It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods. METHODS: We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity. RESULTS: In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n  =  20) and focal (n  =  2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P < 0.001) with similar stability (P < 0.001). Vagal slowing was not observed at sites of AF termination. DISCUSSION: PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF.

Geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation: Findings from the SMASH-AF meta-analysis study cohort.

INTRODUCTION: We performed a systematic review and meta-analysis of geographic and racial representation and reported success rates of studies of catheter ablation for atrial fibrillation (AF). METHODS AND RESULTS: We searched PubMed, Scopus, and Cochrane databases from 1/1/1990 to 8/1/2016 for trials and observational studies reporting AF ablation outcomes. Major exclusion criteria were insufficient reporting of outcomes, non-English language articles, and ablation strategies that were not prespecified and uniform. We described geographic and racial representation and single-procedure ablation success rates by country, controlling for patient demographics and study design characteristics. The analysis cohort included 306 studies (49,227 patients) from 28 countries. Over half of the paroxysmal (PAF) and nonparoxysmal AF (NPAF) treatment arms were conducted in 5 and 3 countries, respectively. Reporting of race or ethnicity demographics and outcomes were rare (1 study, 0.3%) and nonexistent, respectively. Unadjusted success rates by country ranged from 63.5% to 83.0% for PAF studies and 52.7% to 71.6% for NPAF studies, with substantial variation in patient demographics and study design. After controlling for covariates, South Korea and the United States had higher PAF ablation success rates, with large residual heterogeneity. NPAF ablation success rates were statistically similar by country. CONCLUSIONS: Studies of AF ablation have substantial variation in patient demographics, study design, and reported outcomes by country. There is limited geographic representation of trials and observational studies of AF ablation and a paucity of race- or ethnicity-stratified results. Future AF ablation studies and registries should aim to have broad representation by race, geography, and ethnicity to ensure generalizability.

Impact of Race on Outcome of Patients Undergoing Rhythm Control of Atrial Fibrillation.

Racial disparities between African American (AA) and White patients have been documented in cardiovascular disease. We investigated whether these disparities exist in patients undergoing rhythm control for atrial fibrillation (AF). 5873 AF patients (241 AA) were followed to the endpoint of death, stroke, or AF recurrence. Invasive procedures for AF rhythm control were examined in both racial groups. Over a mean follow-up time of 40 months, AA patients had a higher adjusted risk of death [HR 1.39, 95% CI 1.00-1.92, p = 0.043] and stroke [HR 1.90, 95% CI 1.13-3.15, p = 0.013] but a lower risk of AF recurrence [HR 0.79, 95% CI 0.63-0.97, p = 0.026]. In addition, AA patients were less likely to undergo AF ablation (p = 0.006) or surgical maze (p = 0.032) procedures compared to White patients, possibly due to the lower rates of AF recurrence. Significant racial disparities exist in the management and outcomes of AA and White patients undergoing rhythm control management for AF.

Safety and Efficacy of Rivaroxaban in Patients With Cardiac Implantable Electronic Devices: Observations From the ROCKET AF Trial.

BACKGROUND: Although implantation of cardiac implantable electronic devices (CIEDs) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting. METHODS AND RESULTS: Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision. In this post-hoc, postrandomization, on-treatment analysis, only the first intervention per patient was analyzed. During a median follow-up of 2.2 years, 453 patients (242 rivaroxaban group; 211 warfarin group) underwent de novo CIED implantation (64.2%) or revision procedures (35.8%). Patients who received CIEDs were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive CIEDs. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30-day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing. CONCLUSIONS: Bleeding and thromboembolic events were low in both rivaroxaban- and warfarin-treated patients. Periprocedural use of oral factor Xa inhibitors in CIED implantation requires further study in prospective, randomized trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Gender differences in management and clinical outcomes of atrial fibrillation patients.

BACKGROUND: Prior research has identified gender differences in the epidemiology and clinical management of atrial fibrillation (AF). The primary aim of this study is to systematically analyze a cohort of AF men and women and evaluate their baseline demographics, treatment, and clinical outcomes by gender. METHODS: We examined the records of 5976 (42% women) consecutive AF patients who were prescribed at least one anti-arrhythmic drug between 2006 and 2013. From this cohort, 4311 (72%) patients had anticoagulation data available and were included in the final analysis. Time to clinical events was assessed using survival analysis and adjusted for covariates using Cox regression. RESULTS: Compared to men, women were older (73 years vs. 67 years, p<0.001), had higher CHADS2 scores (1.9 vs. 1.5, p<0.001), and fewer cardiac comorbidities. Compared to men, women were more often prescribed sotalol and less often dofetilide (p<0.001). Women were also less likely to be anticoagulated (76.8% vs. 82.5%, p<0.001). Over a mean follow-up of 40 months, women were more likely to die (HR 1.21, p=0.037) or to have an ischemic stroke (HR 1.35, p=0.058). Women also had higher rates of atrioventricular-nodal ablation (adjusted HR 2.11, p<0.001) and pacemaker implantation (adjusted HR 1.69, p<0.001) procedures, but lower rates of electrical cardioversions, AF ablations, and maze surgeries. CONCLUSIONS: There are significant gender differences in baseline demographics and clinical outcomes of AF patients. Women have higher mortality and ischemic strokes and are less often prescribed anticoagulation therapy despite higher CHADS2 scores. These data have important clinical implications.

Large Morel-Lavallée lesion presenting as fungating mass with skin ulceration.

A Morel-Lavallée lesion, a type of soft tissue degloving injury that has also been referred to as a chronic expanding hematoma, is a relatively rare condition that usually develops following traumatic injury. Here, we present a case of a 60-year-old male with a Morel-Lavallée lesion diagnosed over 5 years after a traumatic injury of the hip. He presented with a large fungating mass and overlying skin ulceration, which was highly suspicious for sarcoma. However, lack of other systemic findings and constitutional complaints, as well as negative imaging studies, did not support a diagnosis of malignancy. This information, combined with the history of remote trauma to the affected area, instead led us to suspect the alternative diagnosis of a Morel-Lavallée lesion. The diagnosis was later confirmed by pathology showing a chronic expanding hematoma. To our knowledge, a Morel-Lavallée lesion presenting as a fungating mass has not been previously described.

Comparative effectiveness of antiarrhythmic drugs for rhythm control of atrial fibrillation.

INTRODUCTION: Although there are many different antiarrhythmic drugs (AADs) approved for rhythm management of atrial fibrillation (AF), little comparative effectiveness data exist to guide drug selection. METHODS: We followed 5952 consecutive AF patients who were prescribed amiodarone (N=2266), dronedarone (N=488), dofetilide (N=539), sotalol (N=1718), or class 1C agents (N=941) to the primary end point of AF recurrence. RESULTS: Median follow-up time was 18.2 months (range 0.1-101.6 months). Patients who were prescribed amiodarone had the highest, while patients on class 1C agents had the lowest baseline CHA2DS2-VASc score, Charlson comorbidity index, and burden of comorbid illnesses including coronary artery disease, congestive heart failure, diabetes mellitus, hyperlipidemia, chronic obstructive lung disease, chronic kidney disease, or cancer (p<0.05 for all comparisons). After adjusting for baseline characteristics, using dronedarone as benchmark, amiodarone [hazard ratio (HR) 0.58, p<0.001], class 1C agents (HR 0.70, p<0.001), and sotalol (HR 0.79, p=0.008), but not dofetilide (HR 0.87, p=0.178) were associated with less AF recurrence. In addition, compared to dronedarone, amiodarone and class 1C agents were associated with lower rates of admissions for AF (HR 0.55, p<0.001 for amiodarone; HR 0.71, p=0.021 for class 1C agents) and all-cause mortality was lowest in patients treated with class 1C agents (HR 0.42, p=0.018). The risk of stroke was similar among all groups. CONCLUSION: Compared with dronedarone, amiodarone, class 1C agents, and sotalol are more effective for rhythm control, while dofetilide had similar efficacy. These findings have important implications for clinical practice.

Mortality risk of long-term amiodarone therapy for atrial fibrillation patients without structural heart disease.

BACKGROUND: Amiodarone is often prescribed in the management of atrial fibrillation (AF) but is known to cause significant end-organ toxicities. In this study, we examined the impact of amiodarone on all-cause mortality in AF patients with structurally normal hearts. METHODS: We performed a retrospective cohort analysis of all AF patients with structurally normal hearts who were prescribed antiarrhythmic drugs (AAD) for rhythm control of AF at our institution from 2006 to 2013 (n = 2,077). Baseline differences between the amiodarone (AMIO: n = 403) and other AADs (NON-AMIO: n = 1,674) groups were corrected for using propensity score matching. RESULTS: Amiodarone use as first-line therapy decreased significantly with a higher degree of prescriber specialization in arrhythmia management (31%, 22%, and 9% for primary care physicians, general cardiologists and cardiac electrophysiologists, respectively, p < 0.001). After propensity score matching, baseline comorbidities were balanced between the AMIO and NON-AMIO groups. Over a median follow-up of 28.2 months (range 6.0-100.9 months), amiodarone was associated with increased all-cause (HR 2.41, p = 0.012) and non-cardiac (HR 3.55, p = 0.008) mortality, but not cardiac mortality. AF recurrence and cardiac hospitalizations were similar between the two study groups. CONCLUSIONS: Amiodarone treatment of AF is associated with increased mortality in patients without structural heart disease and therefore should be avoided or only used as a second-line therapy, when other AF therapies fail. Adherence to guideline recommendations in the management of AF patients impacts clinical outcome.

Risk of Stroke and Death in Atrial Fibrillation by Type of Anticoagulation: A Propensity-Matched Analysis.

BACKGROUND: We examined the effect of novel oral anticoagulants (NOACs) compared to warfarin on the risk of death or stroke in atrial fibrillation (AF) patients in every day clinical practice. METHODS: We examined a cohort of 2,836 AF patients, of whom 2,253 were prescribed warfarin and 583 were prescribed an NOAC. Patients with glomerular filtration rate < 30 mg/mL or history of significant valvular heart disease were excluded. Patients were followed to primary end points of death or stroke. Propensity matching was used to adjust for differences in baseline characteristics between the groups. RESULTS: Compared to patients in the NOAC group, patients on warfarin had more comorbidities and higher CHADS2 and CHA2 DS2 -VASc scores (1.7 vs 1.3 for CHADS2 , 2.8 vs 2.2 for CHA2 DS2 -VASc, P < 0.0001 for both). After adjusting for differences in baseline characteristics, NOAC use was associated with significant reduction in all-cause mortality compared to warfarin (hazard ratio [HR] = 0.47, 95% confidence interval [CI; 0.3-0.8], P = 0.006) but not stroke, over a median follow-up of 42.5 months. The difference in mortality persisted after propensity score matching (HR = 0.51, 95% CI [0.28-0.93], P = 0.03). CONCLUSIONS: Compared to warfarin, NOAC use is associated with decreased all-cause mortality but not stroke risk. These data from real-life clinical practice add to existing evidence for decreased mortality among patients prescribed NOACs compared to warfarin.

Patient outcomes according to adherence to treatment guidelines for rhythm control of atrial fibrillation.

BACKGROUND: Although guidelines for antiarrhythmic drug therapy in atrial fibrillation (AF) were published in 2006, it remains uncertain whether adherence to these guidelines affects patient outcomes. METHODS AND RESULTS: We retrospectively evaluated the records of 5976 consecutive AF patients who were prescribed at least 1 antiarrhythmic drug between 2006 and 2013. Patients with 1 or more prescribed antiarrhythmic drugs that did not comply with guideline recommendations comprised the non-guideline-directed group (=2920); the remainder constituted the guideline-directed group (=3056). Time to events was assessed using the survival analysis method and adjusted for covariates using Cox regression. Rates of adherence to the guidelines increased significantly with a higher degree of prescriber specialization in arrhythmias (49%, 55%, and 60% for primary care physicians, general cardiologists, and cardiac electrophysiologists, respectively, P=0.001) for the first prescribed antiarrhythmic drug. Compared to the non-guideline-directed group, the guideline-directed group had higher rates of heart failure, but lower baseline CHADS2-VASc scores (P<0.001) and lower rates of coronary artery disease, valvular disease, hypertension, hyperlipidemia, pulmonary disease, and renal insufficiency (P<0.05 for all). During 45 ± 26 months follow-up, the guideline-directed group had a lower risk of AF recurrence (hazard ratio=0.86, 95% CI=0.80 to 0.93), fewer hospital admissions for AF (hazard ratio=0.87, 95% CI=0.79 to 0.97), and fewer procedures for recurrent AF, including electrical cardioversion, pacemaker implantation, and atrioventricular nodal ablation (P<0.01 for all). The mortality and stroke risks were similar between the groups. CONCLUSIONS: Adherence to published guidelines in the antiarrhythmic management of AF is associated with improved patient outcomes.