Transvenous extraction of conduction system and lumenless pacing leads.

INTRODUCTION: Conduction system pacing (CSP), often accomplished with lumenless pacing leads, is increasingly employed to achieve physiologic ventricular activation. There are limited data on the extraction of these leads. The objective of this study was to describe the safety and efficacy of extraction of CSP pacing leads and compare outcomes with extraction of non-CSP lumenless leads. METHODS: Patients undergoing CSP/non-CSP lumenless lead removal were included. Outcomes of interest included rates of complete procedural success, complications, and successful reimplantation. RESULTS: Overall, 23 patients were included (n = 14 with CSP and n = 9 with non-CSP lumenless leads implanted in the right atrium, right ventricle, or septum). The mean age was 52.7 ± 24.0 years, 30% were female, and the mean lead age was 4.5 ± 4.4 years. The complete procedural success rate was 100%. One serious complication occurred in the non-CSP group but was unrelated to the lead of interest. Manual traction alone was successful in 57% of CSP cases (mean lead age 2.4 ± 1.7 years) and in 11% of non-CSP cases (mean lead age 7.9 ± 5.3 years). Laser sheaths were used in 43% of CSP cases and 89% of non-CSP cases; rotational cutting tools were used in no CSP cases and in 33% of non-CSP cases. Reimplantation in the conduction system was attempted with a left bundle branch pacing lead and successful in 80% (n = 4/5). CONCLUSION: Extraction of CSP and non-CSP lumenless leads is feasible with a high success rate and a good safety profile. CSP reimplantation after extraction is also feasible with good electrical performance.

Indications for Lead Extraction.

Cardiac implantable electronic devices (CIEDs) are being implanted at increasing rates. Patients with CIEDs require more lead management in contemporary clinical practice, given the increased survival of heart failure patients. There are multiple indications for extraction with the strongest class I indications being in patients with CIED infections. Extraction with complete hardware removal is underutilized and often delayed when it is utilized in patients with CIED infections, resulting in higher mortality. Patient and provider preferences are critical to decision-making when considering extraction. Lead extraction referral and management care pathways are needed in order to optimize care for our patients with CIEDs.

Design and Rationale of a Pragmatic Randomized Clinical Trial of Early Dronedarone versus Usual Care to Change and Improve Outcomes in Persons with First-Detected Atrial Fibrillation - The CHANGE AFIB Study.

BACKGROUND: While there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes. METHODS: In this open-label pragmatic clinical trial nested within the Get With The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months. CONCLUSION: CHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes. CLINICALTRIALS: GOV #: - NCT05130268.

Catheter ablation for supraventricular tachycardia and health resource utilization and expenditures: A propensity-matched cohort study.

BACKGROUND: Few data are available regarding temporal patterns of health resource utilization (HRU) and expenditures among patients undergoing catheter ablation for paroxysmal supraventricular tachycardia (PSVT). This study aimed to describe expenditures and HRU in patients with PSVT who underwent catheter ablation compared to a matched cohort of patients on medical therapy alone. METHODS: Using a large US administrative database, we identified adult patients (age 18 to 65 years) with a new PSVT diagnosis between 2008 and 2016. Propensity-score matching was used to assemble a PSVT cohort treated with ablation or medical therapy alone (N = 2556). Longitudinal trends in HRU and expenditures in the 3-years preceding and following PSVT diagnosis were compared. RESULTS: There were no significant differences in expenditures between groups except within the first year after PSVT diagnosis: $48,004 ablation vs. $17,560 medical therapy (p < 0.001). This difference was driven by procedural expenditures, where the mean cost of catheter ablation was $32,057 ± SD 26,737. In Years 2 and 3 post-ablation, HRU and expenditures decreased to the levels associated with the medical therapy group, although fewer ablation patients required any prescription for beta-blockers, calcium channel blockers, or anti-arrhythmic drugs (32% ablation vs. 42% medical therapy group, p < 0.001). CONCLUSION: Catheter ablation reduces medication burden in PSVT, yet health resource use and expenditures were similar beyond 2 years post-ablation when compared to PSVT patients on medical therapy alone. Additional studies are required to better understand drivers of these sustained health expenditures, and barriers to achieving cost-savings for a potentially curative procedure.

Lead Extraction and Mortality Among Patients With Cardiac Implanted Electronic Device Infection.

Importance: Complete hardware removal is a class I recommendation for cardiovascular implantable electronic device (CIED) infection, but practice patterns and outcomes remain unknown. Objective: To quantify the number of Medicare patients with CIED infections who underwent implantation from 2006 to 2019 and lead extraction from 2007 to 2019 to analyze the outcomes in these patients in a nationwide clinical practice cohort. Design, Setting, and Participants: This cohort study included fee-for-service Medicare Part D beneficiaries from January 1, 2006, to December 31, 2019, who had a de novo CIED implantation and a CIED infection more than 1 year after implantation. Data were analyzed from January 1, 2005, to December 31, 2019. Exposure: A CIED infection, defined as (1) endocarditis or infection of a device implant and (2) documented antibiotic therapy. Main Outcomes and Measures: The primary outcomes of interest were device infection, device extraction, and all-cause mortality. Time-varying multivariable Cox proportional hazards regression models were used to evaluate the association between extraction and survival. Results: Among 1 065 549 patients (median age, 78.0 years [IQR, 72.0-84.0 years]; 50.9% male), mean (SD) follow-up was 4.6 (2.9) years after implantation. There were 11 304 patients (1.1%) with CIED infection (median age, 75.0 years [IQR, 67.0-82.0 years]); 60.1% were male, and 7724 (68.3%) had diabetes. A total of 2102 patients with CIED infection (18.6%) underwent extraction within 30 days of diagnosis. Infection occurred a mean (SD) of 3.7 (2.4) years after implantation, and 1-year survival was 68.3%. There was evidence of highly selective treatment, as most patients did not have extraction within 30 days of diagnosed infection (9202 [81.4%]), while 1511 (13.4%) had extraction within 6 days of diagnosis and 591 (5.2%) had extraction between days 7 and 30. Any extraction was associated with lower mortality compared with no extraction (adjusted hazard ratio [AHR], 0.82; 95% CI, 0.74-0.90; P < .001). Extraction within 6 days was associated with even lower risk of mortality (AHR, 0.69; 95% CI, 0.61-0.78; P < .001). Conclusions and Relevance: In this study, a minority of patients with CIED infection underwent extraction. Extraction was associated with a lower risk of death compared with no extraction. The findings suggest a need to improve adherence to guideline-directed care among patients with CIED infection.

Incidence and Predictors of Relapse After Weaning Immune Suppressive Therapy in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a relapsing-remitting disease, and immune suppression (IS) is the mainstay of therapy. Predictors of relapse for patients with CS in remission are not well characterized. We assessed incidence of relapse in consecutive patients with CS treated with high-dose steroids and/or steroid-sparing agents (SSA) in our center from 2000 to 2020. Remission was defined as reaching maintenance therapy (no IS, SSA, and/or prednisone ≤5 mg/d) for ≥1 month. Relapse was defined as recurrence of CS syndrome requiring IS intensification: heart failure, ventricular arrhythmia, decrease in left ventricular ejection fraction, or increased disease burden on imaging. Among 68 patients, the mean age was 50.7±9.0 years; 25 (37%) were women, and 32 (47%) were Black. In total, 59 patients (87%) reached remission. Over a median follow-up of 39.5 months (interquartile range 17.6, 92.5), 28 (48%) relapsed. Greater percentage of late gadolinium enhancement (LGE) on pretreatment magnetic resonance imaging corresponded with increased likelihood of relapse (odds ratio 1.396 per 5% increase [95% confidence interval (CI) 1.04 to 1.88]; p = 0.028). LGE ≥11% predicted elevated risk of relapse (adjusted odds ratio 4.998 [1.34 to 18.64]; p = 0.017). Shorter time to relapse was observed with isolated CS (adjusted hazard ratio 4.084 [1.44,11.56]; p = 0.008) and LGE ≥11% (adjusted hazard ratio 3.007 [1.01, 8.98]; p = 0.049). Approximately 1 in 2 patients with CS in remission experienced relapse. Greater burden of LGE on cardiac magnetic resonance imaging and isolated CS are associated with greater risk of relapse. Future work is needed to refine risk stratification for relapse and to optimize surveillance strategies on the basis of the burden of disease.

Use of Ripple mapping to enhance localization and ablation of outflow tract premature ventricular contractions.

INTRODUCTION: Accurate localization of septal outflow tract premature ventricular contractions (PVCs) is often difficult due to frequent mid-myocardial or protected origin. Compared with traditional activation mapping, CARTO Ripple mapping provides visualization of all captured electrogram data without assignment of a specific local activation time and thus may enhance PVC localization. METHODS: Electroanatomic maps for consecutive catheter ablation procedures for septal outflow tract PVCs (July 2018-December 2020) were analyzed. For each PVC, we identified the earliest local activation point (EA), defined by the point of maximal -dV/dt in a simultaneously recorded unipolar electrogram, and the earliest Ripple signal (ERS), defined as the earliest point at which three grouped simultaneous Ripple bars appeared in late diastole. Immediate success was defined as full suppression of the clinical PVC. RESULTS: Fifty-seven unique PVCs in 55 procedures were included. When ERS and EA were in the same chamber (RV, LV, or CS), the odds ratio for the successful procedure was 13.1 (95% confidence interval [CI] 2.2-79.9, p = .005). Discordance between sites was associated with a higher likelihood of needing multi-site ablation (odds ratio [OR] 7.9 [1.4-4.6; p = .020]). Median EA-ERS distance in successful versus unsuccessful cases was 4.6 mm (interquartile range 2.9-8.5) versus 12.5 mm (7.8-18.5); (p = .020). CONCLUSION: Greater EA-ERS concordance was associated with higher odds of single-site PVC suppression and successful septal outflow tract PVC ablation. Visualization of complex signals via automated Ripple mapping may offer rapid localization information complementary to local activation mapping for PVCs of mid-myocardial origin.

Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial.

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. FINDINGS: Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66-4·15; p<0·0001). Median time to conversion was 17·2 min (95% CI 13·4-26·5) with the etripamil regimen versus 53·5 min (38·7-87·3) with placebo. Prespecified sensitivity analyses of the primary assessment were conducted to test robustness, yielding supporting results. Treatment-emergent adverse events occurred in 68 (50%) of 99 patients treated with etripamil and 12 (11%) of 85 patients in the placebo group, most of which were located at the administration site and were mild or moderate, and all of which were transient and resolved without intervention. Adverse events occurring in at least 5% of patients treated with etripamil were nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%). No serious etripamil-related adverse events or deaths were reported. INTERPRETATION: Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting. FUNDING: Milestone Pharmaceuticals.

Efficacy and Safety of Adjunctive and Primary Use of the TightRail Mechanical Cutting Sheath for Lead Extraction.

BACKGROUND: Rotational cutting tools are increasingly used in transvenous lead extraction. There are limited data on their safety and efficacy, particularly when used adjunctively for stalled progression. The aim of this study was to evaluate the utilization, safety, and effectiveness of mechanical rotational cutting tools for transvenous lead extraction. METHODS: Patients undergoing transvenous lead extraction at a single tertiary center (April 2015 to January 2021, n=586) were included in this retrospective analysis. The study characterized the 251 patients (42.8%) whose cases involved the TightRail mechanical cutting tool. RESULTS: Among 251 patients, 526 leads were extracted and TightRail was used for 70.5%. The TightRail was used adjunctively with the laser for 65.2% of leads, 97.8% of the time as the second tool after stalled progression. Using a multivariable logistic regression model, we found that active-fixation leads (odds ratio, 2.78 [95% CI, 1.62-4.78]; P=0.0002), dual-coil leads (odds ratio, 3.39 [95% CI, 1.87-6.16]; P<0.0001), and lead dwell time (odds ratio, 1.16 [95% CI for 1-year increase, 1.11-1.21]; P<0.0001) were factors independently associated with adjunctive TightRail use. Stalled progression requiring TightRail occurred most often in the innominate vein and superior vena cava (59.3%). The clinical success rate was 96.8%, and the rate of major adverse events was 2.8%. Only 1 major adverse event was observed during TightRail use. CONCLUSIONS: Rotational cutting with TightRail was used in 42.8% of transvenous lead extractions, predominantly in an adjunctive manner after stalled laser progression in the innominate vein and superior vena cava, and more frequently for dual-coil and leads with longer dwell times. Adjunctive TightRail use carries a low risk of major complications.

Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF.

BACKGROUND: There is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction. METHODS: Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from 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]), we performed an individual patient-level network meta-analysis to evaluate the safety and efficacy of DOACs versus warfarin across continuous creatinine clearance (CrCl). A multivariable Cox model including treatment-by-CrCl interaction with random effects was fitted to estimate hazard ratios for paired treatment strategies (standard-dose DOAC, lower-dose DOAC, and warfarin). Outcomes included stroke and systemic embolism (S/SE), major bleeding, intracranial hemorrhage (ICH), and death. RESULTS: Among 71 683 patients (mean age, 70.6±9.4 years; 37.3% female; median follow-up, 23.1 months), the mean CrCl was 75.5±30.5 mL/min. The incidence of S/SE, major bleeding, ICH, and death increased significantly with worsening kidney function. Across continuous CrCl values down to 25 mL/min, the hazard of major bleeding did not change for patients randomized to standard-dose DOACs compared with those randomized to warfarin (Pinteraction=0.61). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of ICH at CrCl values <122 mL/min, with a trend for increased safety with DOAC as CrCl decreased (6.2% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of S/SE with CrCl <87 mL/min, with a significant treatment-by-CrCl effect (4.8% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.01). The hazard of death was significantly lower with standard-dose DOACs for patients with CrCl <77 mL/min, with a trend toward increasing benefit with lower CrCl (2.1% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Use of lower-dose rather than standard-dose DOACs was not associated with a significant difference in incident bleeding or ICH in patients with reduced kidney function but was associated with a higher incidence4 of death and S/SE. CONCLUSIONS: Standard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death. These findings support the use of standard-dose DOACs over warfarin in patients with kidney dysfunction.

Early Lead Extraction for Infected Implanted Cardiac Electronic Devices: JACC Review Topic of the Week.

Infection remains a serious complication associated with the cardiac implantable electronic devices (CIEDs), leading to substantial clinical and economic burden globally. This review assesses the burden of cardiac implantable electronic device infection (CIED-I), evidence for treatment recommendations, barriers to early diagnosis and appropriate therapy, and potential solutions. Multiple clinical practice guidelines recommended complete system and lead removal for CIED-I when appropriate. CIED extraction for infection has been consistently reported with high success, low complication, and very low mortality rates. Complete and early extraction was associated with significantly better clinical and economic outcome compared with no or late extraction. However, significant gaps in knowledge and poor recommendation compliance have been reported. Barriers to optimal management may include diagnostic delay, knowledge gaps, and limited access to expertise. A multipronged approach, including education of all stakeholders, a CIED-I alert system, and improving access to experts, could help bring paradigm shift in the treatment of this serious condition.

Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

Syncope Recurrence and Downstream Diagnostic Testing after Insertable Cardiac Monitor Placement for Syncope.

Despite advances in syncope evaluation strategies and risk stratification, the high cost of syncope is largely driven by extensive and often repetitive testing. This analysis of a large deidentified US claims database compared the use of diagnostic tests, therapeutic procedures, and the recurrence rate of acute syncope events before and after placement of an insertable cardiac monitor (ICM) in syncope patients. The patients had a minimum of 1 year of continuous enrollment before and 2 years after ICM placement. Among 2140 patients identified, a statistically significant reduction in the use of 14 out of 18 tests was observed during follow-up compared with pre-ICM testing. During the 2-year follow-up, 28.3% of patients underwent cardiac therapeutic interventions after a median of 127 days. Significantly fewer patients experienced acute syncope events during the 1st and 2nd years of ICM follow-up compared with the 1-year pre-ICM period, and the frequency of events per patient also decreased. In conclusion, reductions in diagnostic testing and acute syncope events were observed after ICM placement in a large real-world cohort of unexplained syncope patients. Further studies are needed to prospectively assess the impact of ICM vs. short-term monitoring on patient outcomes and healthcare utilization.

Left Atrial Appendage Occlusion Versus Oral Anticoagulation in Atrial Fibrillation : A Decision Analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is a potential alternative to oral anticoagulants in selected patients with atrial fibrillation (AF). Compared with anticoagulants, LAAO decreases major bleeding risk, but there is uncertainty regarding the risk for ischemic stroke compared with anticoagulation. OBJECTIVE: To determine the optimal strategy for stroke prevention conditional on a patient's individual risks for ischemic stroke and bleeding. DESIGN: Decision analysis with a Markov model. DATA SOURCES: Evidence from the published literature informed model inputs. TARGET POPULATION: Women and men with nonvalvular AF and without prior stroke. TIME HORIZON: Lifetime. PERSPECTIVE: Clinical. INTERVENTION: LAAO versus warfarin or direct oral anticoagulants (DOACs). OUTCOME MEASURES: The primary end point was clinical benefit measured in quality-adjusted life-years. RESULTS OF BASE-CASE ANALYSIS: The baseline risks for stroke and bleeding determined whether LAAO was preferred over anticoagulants in patients with AF. The combined risks favored LAAO for higher bleeding risk, but that benefit became less certain at higher stroke risks. For example, at a HAS-BLED score of 5, LAAO was favored in more than 80% of model simulations for CHA2DS2-VASc scores between 2 and 5. The probability of LAAO benefit in QALYs (>80%) at lower bleeding risks (HAS-BLED score of 0 to 1) was limited to patients with lower stroke risks (CHA2DS2-VASc score of 2). Because DOACs carry lower bleeding risks than warfarin, the net benefit of LAAO is less certain than that of DOACs. RESULTS OF SENSITIVITY ANALYSIS: Results were consistent using the ORBIT bleeding score instead of the HAS-BLED score, as well as alternative sources for LAAO clinical effectiveness data. LIMITATION: Clinical effectiveness data were drawn primarily from studies on the Watchman device. CONCLUSION: Although LAAO could be an alternative to anticoagulants for stroke prevention in patients with AF and high bleeding risk, the overall benefit from LAAO depends on the combination of stroke and bleeding risks in individual patients. These results suggest the need for a sufficiently low stroke risk for LAAO to be beneficial. The authors believe that these results could improve shared decision making when selecting patients for LAAO. PRIMARY FUNDING SOURCE: None.

Effect of Mailing Educational Material to Patients With Atrial Fibrillation and Their Clinicians on Use of Oral Anticoagulants: A Randomized Clinical Trial.

Importance: Only about half of patients with atrial fibrillation (AF) who are at increased risk for stroke are treated with an oral anticoagulant (OAC), despite guideline recommendations for their use. Educating patients with AF about prevention of stroke with OACs may enable them as agents of change to initiate OAC treatment. Objective: To determine whether an educational intervention directed to patients and their clinicians stimulates the use of OACs in patients with AF who are not receiving OACs. Design, Setting, and Participants: The Implementation of a Randomized Controlled Trial to Improve Treatment With Oral Anticoagulants in Patients With Atrial Fibrillation (IMPACT-AFib) trial was a prospective, multicenter, open-label, pragmatic randomized clinical trial conducted from September 25, 2017, to May 1, 2019, embedded in health plans that participate in the US Food and Drug Administration's Sentinel System. It used the distributed database comprising health plan members to identify eligible patients, their clinicians, and outcomes. IMPACT-AFib enrolled patients with AF, a CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score of 2 or more, no evidence of OAC prescription dispensing in the preceding 12 months, and no hospitalization-related bleeding event within the prior 6 months. Interventions: Randomization to a single mailing of patient and/or clinician educational materials vs control. Main Outcomes and Measures: Analysis was performed on a modified intention-to-treat basis. The primary end point was the proportion of patients with at least 1 OAC prescription dispensed or at least 4 international normalized ratio test results within 1 year of the intervention. Results: Among 47 333 patients, there were 24 909 men (52.6%), the mean (SD) age was 77.9 (9.7) years, mean (SD) CHA2DS2-VASc score was 4.5 (1.7), 22 404 patients (47.3%) had an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more, and 8890 patients (18.8%) had a history of hospitalization for bleeding. There were 2328 of 23 546 patients (9.9%) in the intervention group with initiation of OAC at 1 year compared with 2330 of 23 787 patients (9.8%) in the control group (adjusted OR, 1.01 [95% CI, 0.95-1.07]; P = .79). Conclusions and Relevance: Among a large population with AF with a guideline indication for OACs for stroke prevention who were randomized to a mailed educational intervention or to usual care, there was no clinically meaningful, numerical, or statistically significant difference in rates of OAC initiation. More-intensive interventions are needed to try and address the public health issue of underuse of anticoagulation for stroke prevention among patients with AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03259373.