Mahaffey, Kenneth W.

Abstract Aims The presence of cancer can complicate treatment choices for patients with atrial fibrillation (AF) increasing both the risk of thrombotic and bleeding events. Methods and results Using data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we aimed to characterize AF patients with cancer, to describe their management and to assess the association between cancer and cardiovascular (CV) outcomes. Among 9749 patients, 23.8% had history of cancer (57% solid malignancy, 1.3% leukaemia, 3.3% lymphoma, 40% other type, and 2.2% metastatic cancer). Patients with history of cancer were older, more likely to have CV disease, CV risk factors, and prior gastrointestinal bleeding. No difference in antiarrhythmic and antithrombotic therapy was observed between those with and without cancer. Patients with history of cancer had a significantly higher risk of death (7.8 vs. 4.9 deaths per 100 patient-years follow-up, P = 0.0003) mainly driven by non-CV death (4.2 vs. 2.4 per 100 patient-years follow-up; P = 0.0004) and higher risk of major bleeding (5.1 vs. 3.5 per 100 patient-years follow-up; P = 0.02) compared with non-cancer patients; no differences were observed in risks of strokes/non-central nervous system embolism (1.96 vs. 1.48, P = 0.74) and CV death (2.89 vs. 2.07, P = 0.35) between the two groups. Conclusion A history of cancer is common among AF patients with up to one in four patients having both. Antithrombotic therapy, rates of cerebrovascular accident, other thrombotic events and cardiac death were similar in AF patients with or without a history of cancer. Patients with cancer, however, were at higher risk of major bleeding and non-CV death.

Background Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation ( AF ). Methods and Results We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation ( OAC ; warfarin or novel oral anticoagulants [ NOAC ]). Secondary outcomes of interest included the proportion of patients prescribed NOAC s (dabigatran or rivaroxaban); time in therapeutic range ( TTR ) for warfarin users, all‐cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P =0.079), but less likely to receive NOAC at baseline or follow‐up (12.1% vs 16.3%; unadjusted P =0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [ OR ]=0.68; 95% CI =0.49, 0.94), but was not associated with OAC use overall ( OR =0.82; 95% CI =0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P <0.0001; adjusted TTR difference, −2.9; 95% CI =−5.7, −0.2; P =0.04). Use of an NOAC over 2 years of follow‐up was not statistically different by insurance. Compared with non‐Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics. Conclusions In a contemporary AF cohort, use of OAC overall and use of NOAC s were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.

ABSTRACTBackgroundPatients with sinus node dysfunction (SND) have increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). To date, treatment patterns and outcomes of patients with SND and AF have not been well described.HypothesisPatients with SND and AF have higher risk of adverse cardiovascular outcomes.MethodsSinus node dysfunction was defined clinically, based on treating physician. Treatment patterns were described and logistic regression analysis performed to assess outcomes.ResultsOverall, 1710 (17.7%) out of 9631 patients had SND at enrollment. Patients with SND and AF had increased comorbid medical illnesses, more severe symptoms (European Heart Rhythm Association class IV: 17.5% vs 13.9%; P = 0.0007), and poorer quality of life (median 12‐month Atrial Fibrillation Effect on Quality of Life score: 79.6 vs 85.2; P = 0.0008). There were no differences in AF management strategy between patients with SND and those without (rate control, 69.7% vs 67.7%; rhythm control, 30.0% vs 32.0%; P = 0.11). After adjustment, patients with SND were more likely than those without SND to progress from paroxysmal AF at baseline to persistent or permanent AF at any follow‐up, or persistent AF at baseline to permanent AF at any follow‐up (odds ratio: 1.23, 95% confidence interval: 1.01‐1.49, P = 0.035). However, there was no association between SND and major risk‐adjusted outcomes.ConclusionsSinus node dysfunction is present in 1 of 6 patients with AF and is associated with increased comorbidities and higher symptom burden. However, SND is not associated with an increase in major risk‐adjusted outcomes.

Background Most patients with atrial fibrillation ( AF ) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF . Methods and Results We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time‐dependent covariate in multivariable Cox models of all‐cause and cause‐specific mortality during a median follow‐up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA 2 DS 2 ‐ VAS c scores, renal function, or left ventricular function. There were significant differences in race ( P =0.001), sinus node dysfunction ( P =0.004), and treatment with calcium‐channel blockers ( P =0.006) and anticoagulation ( P =0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all‐cause mortality (adjusted hazard ratio [ HR ], 1.15 per 5‐bpm decrease; 95% CI , 1.01 to 1.32; P =0.04). Similarly, increasing heart rate >65 bpm was associated with higher all‐cause mortality (adjusted HR , 1.10 per 5‐bpm increase; 95% CI , 1.05 to 1.15; P <0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Conclusions Among patients with permanent AF , there is a J‐shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. Clinical Trial Registration URL : http://clinicaltrials.gov/ . Unique identifier: NCT01165710.

Background— Instruments to assess symptom burden and quality of life among patients with atrial fibrillation (AF) have not been well evaluated in community practice or associated with patient outcomes. Methods and Results— Using data from 10 087 AF patients in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF), symptom severity was evaluated using the European Heart Rhythm Association (EHRA) classification system, and quality of life was assessed using the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire. The association between AF-related symptoms, quality of life, and outcomes was assessed using Cox regression. The majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3–4). EHRA symptom class was well correlated with the AFEQT score (Spearman correlation coefficient −0.39). Over 1.8 years of follow-up, AF symptoms were associated with a higher risk of hospitalization (adjusted hazard ratio for EHRA ≥2 versus EHRA 1 1.23, 95% confidence interval, 1.15–1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted hazard ratio for lowest quartile of AFEQT versus highest 1.49, 95% confidence interval, 1.2–1.84), but not other major adverse events, including death. Conclusions— In a community-based study, most patients with AF were symptomatic and had impaired quality of life. Quality of life measured by the AFEQT correlated closely with symptom severity measured by the EHRA class. AF symptoms and lower quality of life were associated with higher risk of hospitalization but not mortality during follow-up.

Objective Atrial fibrillation (AF) often progresses from paroxysmal or persistent to more sustained forms, but the rate and predictors of AF progression in clinical practice are not well described. Methods Using the Outcomes Registry for Better Informed Treatment of AF, we analysed the incidence and predictors of progression and tested the discrimination and calibration of the HATCH (hypertension, age, TIA/stroke, chronic obstructive pulmonary disease, heart failure) and CHA2DS2VASc scores for identifying AF progression. Results Among 6235 patients with paroxysmal or persistent AF at baseline, 1479 progressed, during follow-up (median 18 (IQR 12–24) months). These patients were older and had more comorbidities than patients who did not progress (CHADS2 2.3±1.3 vs 2.1±1.3, p<0.0001). At baseline, patients with AF progression were more often on a rate control as opposed to a rhythm control strategy (66 vs 56%, p<0.0001) and had higher heart rate (72(64–80) vs 68(60–76) bpm, p<0.0001). The strongest predictors of AF progression were AF on the baseline ECG (OR 2.30, 95% CI 1.95 to 2.73, p<0.0001) and increasing age (OR 1.16, 95% CI1.09 to 1.24, p<0.0001, per 10 increase), while patients with lower heart rate (OR 0.84, 95% CI 0.79 to 0.89, p<0.0001, per 10 decrease ≤80) were less likely to progress. There was no significant interaction between rhythm on baseline ECG and heart rate (p=0.71). The HATCH and CHA2DS2VASc scores had modest discriminatory power for AF progression (C-indices 0.55 (95% CI 0.53 to 0.58) and 0.55 (95% CI 0.52 to 0.57)). Conclusions Within 1.5 years, almost a quarter of the patients with paroxysmal or persistent AF progress to a more sustained form. Progression is strongly associated with heart rate, and age.

Background— Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. Methods and Results— The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P =0.0003) and mechanical valve replacements (9.6% versus 2.4%; P <0.0001); however, there was no difference in CHA 2 DS 2 -VASc scores (scores ≥2 in 94% versus 95%; P =0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P <0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P =0.0001). Conclusions— Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning anticoagulation interruptions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Background Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P <0.0001), more likely to be white (92% versus 89%, P =0.005), more likely to have private insurance (33% versus 25%, P <0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P <0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P <0.0001), lower CHADS 2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P <0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P <0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P =0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P <0.0001). Conclusions Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL : Clinicaltrials.gov. Unique identifier: NCT 01165710.

Background The prevalence of atrial fibrillation ( AF ) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty. Methods and Results Using the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ) Registry, we described patient characteristics and AF management strategies in ambulatory clinic practice settings, including electrophysiology ( EP ), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an EP provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by EP providers were younger (median age, 73 years [interquartile range, IQR , 64, 80 years, Q1, Q3] versus 75 years [ IQR , 67, 82 years] for cardiology and versus 76 years [ IQR , 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers, EP providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively, P <0.0001; adjusted odds ratio [ OR ] EP versus cardiology, 1.66 [95% confidence interval, CI , 1.05 to 2.61]; adjusted OR for internal medicine/primary care versus cardiology, 0.91 [95% CI , 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and EP providers (overall, 76.1%; P =0.02 for difference between groups). Conclusions Our data demonstrate important differences between provider specialties, the demographics of the AF patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.