Piccini, Jonathan P.

Background: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point. Methods: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D–based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective. Results: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360–$27 170) and the lifetime mean cost difference was $15 516 (95% CI, –$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio < $100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained. Conclusions: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

Introduction: Higher body mass index (BMI) is an independent risk factor for incident atrial fibrillation (AF). However, its impact on management strategies and clinical outcomes among patients with prevalent AF is unclear. Methods: The study cohort included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry from June 2010 through August 2011. Participants with BMI > 18.5 kg/m2 were stratified into normal (18.5 - 25 kg/m2), overweight (25 - 30 kg/m2), Class I obese (30 - 35 kg/m2), Class II obese (35 - 40 kg/m2), and Class III obese (>40 kg/m2) categories. Unadjusted and adjusted Cox frailty models were constructed to assess the categorical and continuous association of BMI with AF progression, mortality, and incidence of thromboembolic events. Results: We evaluated 9,606 patients with AF (mean age: 74 + 11 years; 42% women) from 174 US ORBIT participating practices. Patients in the higher BMI categories were younger and had a higher prevalence of comorbidities such as diabetes, hypertension, and obstructive sleep apnea. AF symptom burden was greatest among patients in extreme BMI categories. Proportional use of anticoagulation, antiarrhythmic drugs, and invasive rhythm control strategies was significantly greater among patients in higher BMI categories. Rates for mortality and stroke/non-CNS embolism decreased in a near linear fashion across successively higher BMI categories (P<0.001; Table). After multivariable adjustment, higher BMI categories were associated with lower risk for mortality (p = 0.0002), with the lowest risk observed among overweight patients [Hazard Ratio (HR) (95% CI): 0.65 (0.54 - 0.79) ref. group: normal weight]. For every 5-kg/m2 increase in BMI, the odds of risk-adjusted mortality were 6% lower [HR (95% CI): 0.94 (0.89 - 0.98)]. In contrast, the association between BMI and risk for stroke/non-CNS embolism was significant on unadjusted analysis (P <0.001) but attenuated after adjustment for risk factors (P = 0.78; Table). No significant association was observed between BMI and AF progression rates in either unadjusted (P = 0.35) or adjusted analyses (P = 0.17). Conclusion: Among patients with AF, higher BMI was associated with a greater use of anticoagulation, rhythm control strategies, and lower mortality risk.

Background: Interruption of OAC is often required for invasive procedures, yet the frequency, management, and outcomes of temporary interruptions (TIs) in community practice are unknown. Methods: We assessed the frequency and reasons for TI in outpatients with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF). Patient characteristics and use of bridging anticoagulants were analyzed. Endpoints included periprocedural adverse events (bleeding, thrombotic, or other) and cause-specific hospitalization within 30 days after TI. Results: Overall 7,372 patients were treated with OAC at baseline; 30% (n=2200) required at least 1 TI during median follow-up of 1 year. Patients requiring TI were similar in age (mean age 74 for both) and CHADS2 scores (mean 2.4 for both) to those not requiring TI. Among 3104 interruptions, the most commonly-identified reasons were for non-cardiac surgery (n=827, 27%), followed by endoscopic procedures (n=551, 18%) and cardiac catheterization (n=308, 10%). Bridging anticoagulants were used in 23% (n=709) of interruptions, including low-molecular weight heparin (n=512) or unfractionated heparin (n=109). Rates of bridging were highest during cardiac surgery (44%), cardiac catheterization (32%), and catheter ablation (33%). Patients with a prior stroke or TIA were significantly more likely to receive bridging (35% vs. 25%, p=0.0003), however there was no difference between patients with CHADS2 score >=2 vs. 0-1 (27% vs. 25%, p=NS). Adverse events during interruption were more common in bridged patients (5.1% vs. 2.9%, p=0.02), including bleeding events (3.6% vs. 1.8%, p=0.02); thrombotic events were uncommon (0.7 [n=4] vs. 0.5% [n=10], p=NS). After interruption, adverse events occurred early in follow-up (Figure), and bridged patients were more likely to experience any adverse event (13% vs. 6.3%, p<0.0001), cardiovascular hospitalization (4.3% vs. 2.3%, p=0.02), and bleeding hospitalization (2.2% vs. 0.7%, p=0.002) within 30 days. Conclusions: Temporary interruptions are common in patients receiving OAC for AF, however, bridging anticoagulation is used in a minority. Bleeding events following TI occurred significantly more often in patients receiving bridging anticoagulation.

Background: Dabigatran is a novel oral anticoagulant approved in October 2010 for thromboprophylaxis in atrial fibrillation (AF), yet patterns of adoption of this novel agent in clinical practice are unknown. Methods: Using the ORBIT-AF Registry, a national outpatient prospective AF registry involving 170 sites, we examined patterns of those switching to dabigatran from warfarin from 2010 to 2012. Results: Of 7,066 patients with AF receiving warfarin at baseline, 511 (7%) were switched to dabigatran during follow-up. Patients switched to dabigatran were younger (median age 73 vs. 76, p<0.0001), more likely to be White (94% vs. 89%, p=0.001), and had better kidney function (median creatinine clearance (CrCl) 77 mL/min vs. 69 mL/min, p<0.0001), but less likely to have a history of anemia, (14% vs. 18%, p=0.009) or history of any cerebrovascular disease (14% vs. 17%, p=0.04) or CAD (22% vs. 34%, p<0.0001) or be followed in an anticoagulation clinic (36% vs. 45%, p<0.0001). Patients switched to dabigatran were more likely to have been recently diagnosed with AF (5.3% vs. 3.0%, p=0.03), and their CHADS 2 scores were significantly lower (p<0.0001). Conclusions: Patients receiving warfarin who were switched to dabigatran were younger, with lower CHADS 2 scores, better kidney function, and less concomitant cardiovascular disease than those not switched. This conservative transition pattern suggests greater physician emphasis on bleeding avoidance than on stroke risk reduction.

Background. Oral anticoagulation therapy (OAC) reduces the risk of thromboembolic events associated with atrial fibrillation (AF), yet a substantial proportion of patients with AF are not prescribed OAC. The frequencies of and factors associated with contraindications to OAC therapy in clinical practice are not well-described. Methods. We used data from the ORBIT-AF study, a national, prospective, outpatient registry of incident and prevalent AF. OAC contraindications were uniformly collected at study enrollment by site personnel. Patient and provider characteristics were compared between participants with documented OAC contraindications at baseline and those without OAC contraindications. Results. From June 2010 to August 2011, 10124 patients ≥18 years old with electrocardiographically documented AF were enrolled at 176 practices. Of these, 1409 (13.9%) had OAC contraindications documented at the baseline visit: prior bleed (26.2%), patient refusal/preference (26.0%), high bleeding risk (22.6%), frequent falls/frailty (16.6%), other (11.9%), need for dual antiplatelet therapy (9.8%), unable to adhere/monitor warfarin (5.7%), comorbid illness (5.0%), prior intracranial hemorrhage (4.7%), allergy (2.3%), occupational risk (0.8%), and pregnancy (0.2%). Compared to patients without contraindications, those with contraindications had higher stroke risk (CHADS2>2) and were older, more likely to be female, more likely to be seen by a cardiologist and less likely to be seen by an electrophysiologist (Table 1). Among those patients with reported contraindications, 28.4% were taking warfarin. Conclusions. Contraindications to OAC therapy among AF patients are common and often due to high bleeding risk. Furthermore, many patients with reported contraindications are taking warfarin, suggesting that many contraindications to warfarin therapy are minor, relative, or temporary.

Introduction: Randomized trials have not demonstrated significant differences in stroke, heart failure or mortality between rhythm and rate control strategies for management of atrial fibrillation (AF). The comparative outcomes in contemporary clinical practice are not well described. The objective of this study was to evaluate outcomes in clinical practice with rhythm control versus rate control strategy. Methods: Patients managed with a rhythm control strategy targeting maintenance of sinus rhythm were retrospectively compared with a strategy of rate control alone in a AF registry across various US practice settings. Unadjusted and adjusted (inverse-propensity weighted) outcomes were estimated. Results: The overall study population (n=6988) had a median age of 74 (25th, 75th percentile 65, 81) years, 56% were males, 77% had first detected or paroxysmal AF and 89% had CHA2DS2-VASc score ≥2. In unadjusted analyses, rhythm control was associated with lower all-cause death, cardiovascular death, first stroke/non-central nervous system systemic embolization/transient ischemic attack, or first major bleeding event (all p<0.05); however, rhythm control was associated with more cardiovascular hospitalizations (HR 1.24, 95% CI 1.10-1.39, p=0.0003; Figure). Conclusion: Among patients with AF in clinical practice, rhythm control was not superior to rate control strategy for outcomes of stroke, heart failure, or mortality, but was associated with more cardiovascular hospitalizations.

Background: Little information exists on clinical characteristics and treatment patterns of patients with atrial fibrillation (AF) following a major bleeding event in clinical practice. Methods: We used data from a large, national outpatient registry, ORBIT-AF (2010 – 2011), to evaluate event characteristics and oral anticoagulation (OAC) management following a major bleeding event. Major bleeds were defined according to ISTH criteria. We compared baseline characteristics among patients who persisted on OAC therapy at the first clinic visit following a major bleed and those in whom OAC was discontinued using chi-squared tests. Results: Of 10135 patients enrolled in ORBIT-AF, n=791 (7.8%) bleeding events occurred during 2 years of follow-up. Among patients who were receiving OA, n=632 (3.5 per 100 person years) experienced a major bleed. Of these, 67.3% experienced a fall in hemoglobin and 46.8% required transfusion of 2 of more units of red blood cells. Critical site bleeding occurred in 150 OAC patients, with the majority of these classified as intracranial bleeding (n= 89), followed by retroperitoneal (n=25) and intraocular (n=17). Fatal bleeds occurred in 37 patients (5.9% of all major bleeds). Nearly one-third of patients (31.0%) discontinued OAC therapy following the major bleeding event. Compared with those who persisted on OAC, patients who discontinued OAC were more likely to have hypertension and CKD. Those who discontinued OAC were more likely to have gastrointestinal or CNS site bleeding compared with those who persisted (Table). Conclusions: One in three patients who experienced a major bleed were no longer optimally anticoagulated after the event. Those who discontinued OAC had a greater comorbidity burden and more likely to have bleeding in a critical site those who persisted on OAC.

Introduction Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation. Methods and analysis We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings. Ethics and dissemination The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals. Trial registration number NCT04468321

Background: The use of evidence-based therapies to treat cardiovascular comorbidities and risk factors in patients with AF in outpatient clinical practice has not been well characterized. Methods: Using a large, community-based registry of patients with AF in the United States, the prevalence of cardiovascular comorbidities and corresponding use of evidence-based therapies were determined. Results: Among 9,589 enrolled patients with AF, the median age was 75 years; 57.8% were male; 10.7% were non-white; 69.9% had Medicare or Medicaid; 31.8% had coronary heart disease, 32.2% had heart failure, 13.0% had peripheral vascular disease, and 29.5% had diabetes mellitus. Among eligible patients, 62.8% of 3,612 were prescribed an antiplatelet agent, 72.1% of 4,674 were prescribed a β-blocker, 59.7% of 5,121 were prescribed an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 15.7% of 624 were prescribed an aldosterone antagonist, 70.1% of 6,914 were prescribed a statin, 94.7% of 8,329 were prescribed an antihypertensive, 58.3% of 504 had an ICD, and 44.5% of 9,589 received all indicated evidence-based therapies ( Table ). Conclusion: Cardiovascular comorbidities and risk factors in patients with AF are often inadequately treated with evidence-based therapies in the outpatient practice setting, underscoring opportunities to improve care for patients with AF.

Background: The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) survey has recently been validated to measure the impact of atrial fibrillation on patients’ quality of life, but a clinically important difference (CID) in AFEQT score has not been defined. Knowing the CID is needed to interpret the meaningfulness of differences between treatments in clinical trials; or patient populations for quality assessment. Objectives: To calculate CID values in AFEQT in the ORBIT registry. Methods: ORBIT-AF is a US-based outpatient AF registry that measured disease-specific QoL with the AFEQT tool (score range= 0 (worst) to 100) at baseline and at 1 year follow-up. Two anchor-based methods were used to relate changes in AFEQT to clinically important differences in the more established European Heart Rhythm Association (EHRA) measure of functional status. Ranging from 1 (no symptoms) to 4 (disabling), a change of 1 EHRA class was defined as an important change in the anchor. Both the mean change and receiver operating characteristics (ROC) methods were then used to identify CIDs in AFEQT at 1 year follow-up. This was done for both improvement and worsening on the anchor. The mean change method defines a CID as the mean change in AFEQT score among patients with a 1 EHRA class change. The ROC method identifies a CID as the point on the ROC curve that best discriminates patients who experienced an important change in the anchor (≥ 1 EHRA class change) from those who experienced no change. Results: AFEQT was assessed in 2008 AF patients at baseline and 1347 patients at 1 year from 99 US sites participating in ORBIT-AF. CIDs and 95% confidence intervals (CI) corresponding to an improvement in EHRA for the mean change method were 5.4 (3.6, 7.2) AFEQT points and 1.9 (0.4, 9.3) AFEQT points for the ROC method. CIDs corresponding to worsening in EHRA for the mean change method were -4.2 (-6.9,-1.5) AFEQT points and -7.4 (-13.9,-4.6) AFEQT points for the ROC method. Conclusions: Changes in AFEQT as small as 2 points may be clinically relevant, although CIDs vary depending on the method of calculation. The variability suggests identifying a single universal CID to assess improvement in quality of life in AF patients may not be ideal and improvement may relate to the nature of a patient’s symptoms and their baseline level of activity.