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1.
Heart ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911503

RESUMO

OBJECTIVE: Non-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline. METHODS: We included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing. RESULTS: Among 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of -6.63 mL/min for NOACs and -6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year. CONCLUSIONS: In the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction.

2.
Am Heart J ; 219: 128-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31862084

RESUMO

BACKGROUND: Reducing atrial fibrillation (AF)-related stroke requires timely AF diagnosis, but the optimal monitoring strategy is unknown. OBJECTIVE: We used insertable cardiac monitor (ICM) data from the REVEAL AF study to compare AF detection rates by various short-term continuous monitoring (STM) strategies. METHODS AND RESULTS: Patients without known AF, but with CHADS2 scores ≥3 (or = 2 with ≥1 additional AF risk factor) received an ICM for AF detection. One-time STM strategies were assessed by computing AF incidence at 1, 2, 7, 14, and 30 days post-ICM insertion. Repeated STM strategies (quarterly 24-hour, 48-hour, 7-day, or monthly 24-hour monitoring) were modeled by randomly selecting day(s) within a 30-day window around each nominal evaluation date over a 1-year period (simulated 10,000 times). Endpoints included AF ≥6 minutes, AF ≥1 hour, and daily AF burden ≥1 and ≥ 5.5 hours. The impact of compliance on AF detection was evaluated using daily compliance rates of 85%, 75%, 65% and 55% during follow-up months 1-3, 4-6, 7-9, and 9-12, respectively. Based on data from 385 patients (71.5 ±â€¯9.9 years; CHADS2 score 3.0 ±â€¯1.0) the incidence of AF ≥6 minutes via ICM at 12 months was 27.1% (95% CI, 22.5-31.5%). This exceeded the range of estimated rates from all modeled one-time and repeated STM strategies (0.8% for 24-hour Holter monitoring to 10.6% for quarterly 7-day monitoring). Findings were similar for all AF endpoints. Modeled non-compliance reduced AF detection by 4.5% to 22.9%. CONCLUSIONS: Most AF episodes detected via ICMs would go undetected via conventional STM strategies, thus preventing optimal prophylaxis for adverse consequences.

3.
Am Heart J ; 220: 145-154, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31812756

RESUMO

BACKGROUND: Amiodarone is the most effective antiarrhythmic drug (AAD) for atrial fibrillation (AF), but it has a high incidence of adverse effects. METHODS: Using the ORBIT AF registry, patients with AF on amiodarone at enrollment, prescribed amiodarone during follow-up, or never on amiodarone were analyzed for the proportion treated with a guideline-based indication for amiodarone, the variability in amiodarone use across sites, and the outcomes (mortality, hospitalization, and stroke) among patients treated with amiodarone. Hierarchical logistic regression modeling with site-specific random intercepts compared rates of amiodarone use across 170 sites. A logistic regression model for propensity to receive amiodarone created a propensity-matched cohort. Cox proportional hazards modeling, stratified by matched pairs evaluated the association between amiodarone and outcomes. RESULTS: Among 6,987 AF patients, 867 (12%) were on amiodarone at baseline and 451 (6%) started on incident amiodarone during the 3-year follow-up. Use of amiodarone varied among sites from 3% in the lowest tertile to 21% in the highest (p<0.0001). Among those treated, 32% had documented contraindications to other AADs or had failed another AAD in the past. Mortality, cardiovascular hospitalization, and stroke were similar among matched patients on and not on amiodarone at baseline, while incident amiodarone use in matched patients was associated with higher all-cause mortality (adjusted HR 2.06, 95% CI 1.35-3.16). CONCLUSIONS: Use of amiodarone among AF patients in community practice is highly variable. More than 2 out of 3 patients treated with amiodarone appeared to be eligible for a different AAD.

4.
Circ Arrhythm Electrophysiol ; 12(12): e007612, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31830822

RESUMO

BACKGROUND: Studies evaluating the effects of atrial fibrillation (AF) catheter ablation versus antiarrhythmic therapy on outcomes have shown mixed results. In addition, guidelines recommend continuing oral anticoagulation (OAC) after ablation for those at risk of stroke, but real-world data are lacking. METHODS: We evaluated outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding, and hospitalization in patients undergoing AF ablation compared with a propensity score matched cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registries. Cox proportional hazards regression was performed to evaluate the association between AF ablation and outcomes. We then evaluated patterns of treatment with OAC among AF ablation patients. RESULTS: Among 21 595 patients, 1190 (6%) underwent de novo AF ablation. Our propensity score-matched cohort included 1087 patients who underwent AF ablation matched 1:1 with 1087 patients treated with antiarrhythmic medications only. There were no significant differences in the risk of all-cause and cardiovascular death, and most other major adverse cardiovascular and neurological events. AF catheter ablation was associated with an increased risk of all-cause hospitalization during follow-up (hazard ratio, 1.24 [95% CI, 1.05-1.46]), particularly in the first 3 months (the standard blanking period) after the procedure. Among those who underwent AF ablation with a CHA2DS2 VASc score ≥2 for men and ≥3 for women, 23% had OAC discontinued after ablation. Among those who discontinued OAC, the median time to discontinuation was 6.2 months. CONCLUSIONS: In this large US national registry, we found no difference in adjusted rates of cardiovascular or all-cause death between patients treated with AF catheter ablation and antiarrhythmic medications only. Notably, discontinuation of OAC after ablation remains relatively common despite guideline recommendations for continued stroke prevention therapy in patients at risk of stroke.

5.
Clin Cardiol ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31872901

RESUMO

BACKGROUND: The role of antiarrhythmic drugs for atrial fibrillation/atrial flutter (AF/AFL) after catheter ablation is not well established. HYPOTHESIS: We hypothesized that changing the myocardial substrate by ablation may alter the responsiveness to dronedarone. METHODS: We assessed the efficacy and safety of dronedarone in the treatment of paroxysmal/persistent atrial fibrillation/atrial flutter (AF/AFL) post-ablation, based on a post hoc analysis of the ATHENA study. A total of 196 patients (dronedarone 90, placebo 106) had an ablation for AF/AFL before study entry. In these patients, the effect of treatment on the first hospitalization because of cardiovascular (CV) events/all-cause death was assessed, as was AF/AFL recurrence in individuals with sinus rhythm at baseline. The safety of dronedarone vs placebo was also determined. RESULTS: In patients with prior ablation, dronedarone reduced the risk of AF/AFL recurrence (hazard ratio [HR]: 0.65 [95% confidence interval [CI]: 0.42, 1.00]; P < .05) as well as the median time to first AF/AFL recurrence (561 vs 180 days) compared with placebo. The HR for first CV hospitalization/all-cause death with dronedarone vs placebo was 0.98 (95% CI: 0.62, 1.53; P = .91). Rates of treatment-emergent adverse events were 83.1% vs 75.5% and rates of serious TEAEs were 27.0% vs 18.9% in the dronedarone and placebo groups, respectively. One death occurred with dronedarone (not treatment-emergent) and five occurred with placebo. CONCLUSION: In patients with prior ablation for AF/AFL, dronedarone reduced the risk of AF/AFL recurrence compared with placebo, but not the risk of first CV hospitalization/all-cause death. Safety outcomes were consistent with those of the overall ATHENA study.

6.
J Am Coll Cardiol ; 74(19): 2376-2378, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31699277
7.
Clin Pharmacol Ther ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31709525

RESUMO

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration-sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate the progress in the development of a new cardiac safety paradigm, the Comprehensive in Vitro Proarrhythmia Assay (CiPA). The opinions regarding these principles reflect the collective views of those who participated in the discussion of this topic both at and after the breakout session. Although primarily discussed in the context of in silico models, these principles describe the interface between experimental input and model-based interpretation and are intended to be general enough to be applied to other types of nonclinical models for proarrhythmia assessment. This document was developed with the intention of providing a foundation for more consistency and harmonization in developing and validating different models for proarrhythmia risk prediction using the example of the CiPA paradigm.

8.
JAMA Cardiol ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31268487

RESUMO

Importance: Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range. Objective: To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events. Design, Setting, and Participants: In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019. Exposures: Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range. Main Outcomes and Measures: Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models. Results: A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk. Conclusions and Relevance: Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

9.
Am J Cardiol ; 124(6): 864-870, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31303247

RESUMO

The REVEAL AF study demonstrated a high incidence of previously undetected atrial fibrillation (AF) using insertable cardiac monitors (ICMs) in patients with risk factors for AF and stroke. This analysis evaluated whether ICM monitoring led to changes in clinical management after AF detection. Patients with CHADS2 scores ≥3 (or =2 with ≥1 additional AF risk factor) but no history of AF received an ICM and were followed 18 to 30 months. Physicians recorded changes in clinical management in response to AF detection at scheduled (every 6 months) and unscheduled follow-up visits. Changes in clinical management included oral anticoagulation, rhythm or rate control pharmacotherapy, cardioversion, ablation, and cardiac subspecialist referral. In 387 patients who met inclusion criteria and received an ICM, AF was found in 115. A change in clinical management was taken in 87 patients with AF (76%). In 80 of these 87, a change was taken at the first visit after AF detection. In total, 31 patients (27%) with AF had ≥2 visits at which changes in clinical management were taken. The most common change was initiation of oral anticoagulation (n = 73, 63% of patients with AF). Patients with a change in clinical management at the first visit after AF detection tended to have longer AF episodes and a higher maximal daily AF burden compared with AF patients for whom no change was taken (longest episode: 52 vs 28 minutes; maximal daily AF burden:112 vs 23 minutes). Changes in management more frequently occurred at visits where patients reported AF-compatible symptoms (65% vs 46% of visits, p = 0.01). In conclusion, ICM monitoring to identify AF guides both immediate and long-term patient management in a population at high risk for stroke.

10.
Am Heart J ; 213: 81-90, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129441

RESUMO

BACKGROUND: Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized. METHODS: Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics. RESULTS: Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25]). CONCLUSIONS: Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes.

11.
Circ Cardiovasc Qual Outcomes ; 12(5): e005358, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092022

RESUMO

Background The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire has recently been validated to measure the impact of atrial fibrillation on quality of life, but a clinically important difference in AFEQT score has not been well defined. Methods and Results To determine the clinically important difference in overall AFEQT (score range= 0 [worst] to 100 [best]) and selected subscales, we analyzed data in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry, a United States-based outpatient atrial fibrillation registry. AFEQT was assessed at baseline and 1 year in a subset of 1347 ORBIT-AF patients from 80 US sites participating in ORBIT-AF from June 2010 to August 2011. The mean change method was used to relate changes in 1-year AFEQT scores to clinically important changes in the physician assessment of European Heart Rhythm Association functional status (1 class improvement and separately 1 class deterioration). Clinically important differences and 95% CI corresponding to either a 1 European Heart Rhythm Association class improvement or deterioration were 5.4 (3.6-7.2) and -4.2 (-6.9 to -1.5) AFEQT points, respectively. Similarly, clinically important difference values were seen for a 1 European Heart Rhythm Association class improvement for the AFEQT subscales Activities of Daily Living and Symptoms: 5.1 (2.5-7.6) and 7.1 (5.3-9.0) AFEQT points, respectively. Conclusions Based on the anchor of 1 European Heart Rhythm Association class change, changes in AFEQT score of + or -5 points are clinically important changes in patients' health. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT01165710.

12.
Arrhythm Electrophysiol Rev ; 8(2): 99-104, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31114683

RESUMO

Ventricular arrhythmias are a therapeutic challenge, owing to their relatively unpredictable and deadly nature. Many patients are treated with an implantable cardioverter-defibrillator for either primary or secondary prevention of ventricular arrhythmias, meaning those who are at high risk of versus those who have experienced ventricular arrhythmias or sudden cardiac arrest, respectively. Despite the life-saving benefit, ICD comes with the risk of recurrent shocks for both appropriate and inappropriate rhythms. Patients with recurrent shocks have a poor quality of life and increased mortality rates. In this article, we review data for optimal device settings, medical management and radiofrequency ablation strategies to minimise the frequency of ICD shock, with a focus on treatment of ventricular arrhythmias, to reduce patient morbidity and mortality, and to maximise wellbeing and quality of life.

13.
J Am Heart Assoc ; 8(9): e011205, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31023126

RESUMO

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA 2 DS 2- VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

14.
Cardiol Clin ; 37(2): 197-206, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30926021

RESUMO

Heart failure (HF) and atrial fibrillation (AF) are the epidemics of the twenty-first century. These often coexist and are the cause of major morbidity and mortality. Management of these patients has posed a significant challenge to the medical community. Guideline-directed pharmacologic therapy for heart failure is important; however, there is no clear consensus on how best to treat AF with concomitant HF. In this article, we provide an in-depth review of the management of AF in patients with HF and provide insight as to why catheter ablation should not be the first line of therapy in this population.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Tomada de Decisões , Insuficiência Cardíaca/terapia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Fibrilação Atrial/epidemiologia , Comorbidade , Saúde Global , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Resultado do Tratamento
15.
Am J Cardiol ; 123(10): 1628-1636, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30846214

RESUMO

Systolic blood pressure (SBP) and its association with clinical outcomes in atrial fibrillation (AF) patients in community practice are poorly characterized. In patients with AF, we sought to (1) examine the prevalence of baseline uncontrolled hypertension and the overall change in SBP control, (2) identify predictors of uncontrolled SBP over 2 years of follow-up, and (3) determine the relation between SBP and clinical outcomes. We analyzed 10,132 patients with AF at 176 clinics in the ORBIT-AF registry between 2010 and 2014, classified as: (1) no history of hypertension; (2) controlled hypertension (baseline SBP <140 mm Hg); (3) and uncontrolled hypertension (baseline SBP >140 mm Hg). Predictors of SBP >140 mm Hg at baseline or in follow-up were identified with pooled logistic regression. Random effects Cox regression models were used to compare cardiovascular outcomes and major bleeding as a function of continuous, time-dependent SBP. Overall 8,383 (83%) of patients with AF had hypertension. Of these, 24.2% (n = 2032) had uncontrolled baseline SBP, with little change over 2 years. Predictors of elevated follow-up SBP included uncontrolled baseline SBP, females, previous percutaneous coronary intervention, and diabetes. For every 5 mm Hg increase in follow-up SBP, the adjusted risk of stroke or systemic embolism or transient ischemic attack (adjusted hazard ratio [aHR] 1.05, 95% confidence interval [CI] 1.01 to 1.08, p = 0.01), myocardial infarction (aHR 1.05, 95% CI 1.00 to 1.11, p = 0.04), and major bleeding (aHR 1.03, 95% CI 1.00 to 1.06, p = 0.04) increased modestly. In conclusion, in patients with AF, higher SBP was associated with increasing adverse events; therefore, more rigorous blood pressure control should be emphasized.

16.
Am Heart J ; 211: 77-89, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30901602

RESUMO

BACKGROUND: The incidence of cognitive impairment and frailty increase with age and may impact both therapy and outcomes in atrial fibrillation (AF). METHODS: We examined the prevalence of clinically recognized cognitive impairment and frailty (as defined by the American Geriatric Society Criteria) in the Outcomes Registry for Better Informed Care in AF (ORBIT AF) and associated adjusted outcomes via multivariable Cox regression. The interaction between cognitive impairment and frailty and oral anticoagulation (OAC) in determining outcomes was examined. RESULTS: Among 9749 patients with AF [median (IQR) age 75 (67-82) y, 57% male], cognitive impairment and frailty was identified in 293 (3.0%) and 575 (5.9%) patients respectively. Frail patients (68 vs 77%, P < .001) and those with cognitive impairment (70 vs 77%, P = .006) were both less likely to receive an OAC. Both cognitive impairment [HR (95% CI) 1.34 (1.05-1.72), P = .0198] and frailty [HR 1.29 (1.08-1.55), P = .0060] were associated with increased risk of death. Cognitive impairment and frailty were not associated with stroke/transient ischemic attack (TIA) or major bleeding. In multivariable analysis, there was no interaction between OAC use and cognitive impairment or frailty in their associations with mortality, major bleeding and a composite end point of stroke, non-central nervous system systemic embolism, TIA, myocardial infarction or cardiovascular death. CONCLUSION: Those with cognitive impairment or frailty in AF had higher predicted risk for stroke and higher observed mortality, yet were less likely to be treated with OAC. Despite this, the benefits of OAC were similar in patients with and without cognitive impairment or frailty.

17.
JAMA ; 321(13): 1261-1274, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30874766

RESUMO

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Ablação por Cateter , Parada Cardíaca/prevenção & controle , Hemorragia/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Ablação por Cateter/efeitos adversos , Feminino , Parada Cardíaca/etiologia , Hemorragia/etiologia , Hospitalização/estatística & dados numéricos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/etiologia
18.
19.
Eur Heart J Cardiovasc Pharmacother ; 5(1): 21-28, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30052825

RESUMO

Aims: Antiarrhythmic drugs (AADs) for the treatment of atrial fibrillation (AF) are associated with limited efficacy and adverse effects. Inhibition of the atrial current IKur, absent from the ventricle, is expected to be antiarrhythmic, without adverse cardiac effects, particularly ventricular pro-arrhythmic effects. Methods and results: A randomized clinical trial in symptomatic paroxysmal AF patients being considered for ablation. The primary endpoint was AF burden (AFB) as measured by insertable continuous monitoring (ICM) devices. Screened patients had an ICM implanted and were included if AFB was between 1% and 70% after 4 weeks of recording. They were randomly allocated to 4-week treatment of a selective IKur inhibitor S66913 (5 mg, 25 mg, or 100 mg orally per day) or placebo. The study was to enroll 160 patients. The study was terminated prematurely, due to non-study related preclinical safety concerns, after 58 patients had been enrolled. The median AFB ranged from 4.3% to 10.3% at baseline in the four treatment groups. S66913 had no significant effect on AFB or on AFB plus atrial tachycardia (AT) burden, at any dosage; nor on any secondary endpoints including the number and duration of AT or AF episodes, and symptoms. The drug was well tolerated with no safety concern during the treatment or the extended clinical follow-up. Conclusions: DIAGRAF-IKUR was the first study to show that using ICM to assess the effect of an AAD is feasible. The selective IKur inhibitor S66913 was safe but had no clinically meaningful effect at the time of early termination of the study.


Assuntos
Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Compostos Orgânicos/administração & dosagem , Bloqueadores dos Canais de Potássio/administração & dosagem , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Austrália , Canadá , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Orgânicos/efeitos adversos , Bloqueadores dos Canais de Potássio/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
Int J Cardiol ; 274: 152-157, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30144994

RESUMO

BACKGROUND: Renal function has been associated with an increased stroke risk in patients with atrial fibrillation (AF). However, whether renal function incrementally adds to risk prediction in both anticoagulated and non-anticoagulated patients with AF is unclear. METHODS: We used data from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)-a national, prospective, outpatient AF registry in patients aged >18 years (2010-2011). The association between baseline renal function and risk of stroke/systemic embolism (SSE) was evaluated in proportional hazards models adjusting for stroke risk score components. We compared discrimination of 2-year outcomes using C-indices and evaluated calibration by comparing event rates in ORBIT-AF to published rates from an external clinical trial population (ROCKET AF) and an observational cohort (ATRIA). RESULTS: Among 9743 patients included in the analysis, the median age was 75 years (interquartile range [IQR] 67-82), 89.5% were white, 43% were female, and 76% were taking oral anticoagulation (OAC). Over a median follow-up of 2.3 years, 214 SSE events occurred (1.00 per 100 patient-years). Continuous creatinine clearance (CrCl) was not associated with SSE risk after adjusting for other clinical factors (components of CHADS2 or CHA2DS2-VASc). Discrimination for predicting stroke (C-index; 95% CI) was similar for R2CHADS2 (0.65; 0.61-0.69), CHADS2 (0.65; 0.61-0.69), and CHA2DS2-VASc (0.66; 0.62-0.70). CONCLUSIONS AND RELEVANCE: In a community patient population with AF, renal dysfunction was not independently associated with embolic risk beyond other established risk factors in either OAC-treated or untreated patients. Additional study is needed to identify clinical factors that incrementally add to stroke risk prediction.


Assuntos
Fibrilação Atrial/complicações , Isquemia Encefálica/etiologia , Rim/fisiopatologia , Sistema de Registros , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/fisiopatologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/prevenção & controle , Creatinina/sangue , Feminino , Seguimentos , Humanos , Incidência , Testes de Função Renal , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
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