Efficacy and safety of once-daily carvedilol in patients with atrial fibrillation: A randomized, double-blind, placebo-controlled trial
Jong‐Il ChoiYae Min ParkYong‐Seog OhJin‐Bae KimSeongwook HanJong Sung ParkYoung Keun OnKee‐Joon ChoiGyo‐Seung HwangMoon‐Hyoung LeeDong‐Gu ShinNam‐Ho KimDae-Kyeong KimJune NamgungDae-Hyeok KimHyung Wook ParkHwan-Cheol ParkEue‐Keun ChoiKyoung Suk RheeSeung Yong ShinYoung‐Hoon Kim
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Heart rate (HR) control is a mainstay of atrial fibrillation (AF) management. Guidelines recommend first-line β-blockers for HR control in paroxysmal, persistent, or permanent AF.1January C.T. Wann S. Alpert J.S. et al.2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2014; 64: e1-e76Crossref PubMed Scopus (3017) Google Scholar Carvedilol, a non-selective β-blocker, has a documented HR-lowering effect; in a dose-escalation study of Japanese patients with chronic AF (AF Carvedilol study), each dose of carvedilol (5, 10 or 20 mg, once daily) significantly reduced HR from baseline (HR ≥80 bpm) during 6 weeks of treatment.2Inoue H. Atarashi H. Okumura K. et al.Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study.J Cardiol. 2017; 69: 293-301Abstract Full Text Full Text PDF PubMed Google Scholar Although off-label carvedilol indications include AF,3Singh S. Carvedilol. 2022; Accessed February 23, 2024. https://www.statpearls.com/ArticleLibrary/viewarticle/102Google Scholar there are currently no phase 3 clinical trial data to support carvedilol use for HR control in patients with AF. We report results from a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of patients with persistent or permanent AF treated with once-daily carvedilol (Dilatrend® SR Capsule, Chong Kun Dang Pharmaceutical, Seoul, Republic of Korea) 8, 16 or 32 mg for 6 weeks (NCT03950843). Eligible patients who received carvedilol during the 6-week treatment period entered a 4-week open-label extension. Overall, 154 subjects were enrolled (safety analysis set [SAS]). Subjects in the full analysis set received carvedilol (n = 93) or placebo (n = 42): mean (SD) age 66.4 (9.6) years, mostly male (72.6%), with a mean (SD) resting HR of 98.3 (14.7) bpm, and CHA2DS2-VASc score of 2.43 (1.64), and the majority (80.7%) had a modified European Heart Rhythm Association (EHRA) score of 2a. Most subjects had persistent AF (77.0%) and the mean (SD) AF duration was 60.7 (73.8) months. There were no significant between group differences in baseline characteristics. Change in 24-hour mean HR from baseline to week 6 (primary endpoint) was reduced significantly by carvedilol vs. placebo (P < 0.0001; Figure 1A); changes were maintained in the 4-week extension period. Post-hoc subgroup analysis showed that changes in 24-hour mean HR from baseline to week 6 with carvedilol were dose-dependent: respective mean (SD) changes for carvedilol 8 mg (n = 14), 16 mg (n = 26), and 32 mg (n = 53) were −5.07 (5.97), −9.69 (6.34), and −7.58 (8.00) (P = 0.0072, P < 0.0001, and P < 0.0001, respectively). More subjects achieved HR <80 bpm at week 6 (secondary endpoint) in carvedilol vs. placebo groups (30.1% vs. 14.3%; P = 0.0499), with a risk difference of 15.82 (95% confidence interval: 1.72–29.93). Carvedilol was associated with significant improvement in modified EHRA scores from baseline to week 6 (P < 0.0001; secondary endpoint). Mean hourly HR at baseline was similar between the two groups (Figure 1B, upper panel) but, at week 6, carvedilol produced significant changes from baseline in mean HR at each hourly time point. In contrast, no significant changes from baseline in hourly mean HR were found in the placebo group. At week 6, modest but significant decreases in mean hourly HR were generally observed with carvedilol compared to placebo during the daytime, but there were fewer significant between-group differences at nighttime (exploratory endpoints; Figure 1B, lower panel). In the SAS, 60 treatment-emergent adverse events (TEAEs) were reported in 43 subjects (27.9%) during the 6-week trial: 43 AEs in 31 subjects (29.8%) in the carvedilol group, and 17 in 12 subjects (24.0%) in the placebo group. Most TEAEs were mild (41 cases) or moderate (18 cases) in severity. The most common TEAEs were dizziness in 9 subjects (5.8%) and dyspnea in 7 subjects (4.6%). This is the first pivotal phase 3 clinical trial to show the efficacy of once-daily carvedilol for HR control in patients with AF. Compared with placebo, carvedilol significantly decreased 24-hour mean HR from baseline to week 6 and this effect was maintained during the 4-week extension period. Changes were dose-dependent with higher carvedilol doses (16 and 32 mg) effecting larger changes than the 8 mg dose. Similar results were reported in the AF Carvedilol Japanese trial of patients with persistent or permanent AF, which demonstrated that once-daily carvedilol significantly reduced HR from baseline during 6 weeks of treatment.2Inoue H. Atarashi H. Okumura K. et al.Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study.J Cardiol. 2017; 69: 293-301Abstract Full Text Full Text PDF PubMed Google Scholar In conclusion, carvedilol for 6 weeks was effective in reducing HR in patients with AF and maintained efficacy during the extension period. Carvedilol was well tolerated and the safety profile was consistent with previous reports.Keywords:
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Atrial fibrillation and atrial flutter are the most common dysrhythmias seen in the emergency department. As the aging population continues to grow, atrial fibrillation and atrial flutter are expected to affect 6 million people by 2050. This will lead to an increase in emergency department visits for symptoms from the disease itself or its complications, such as heart failure or thromboembolic disease. This review examines the recent literature on the diagnosis and management of atrial fibrillation. Evidence-based recommendations are provided, including cost-effective strategies to evaluate new-onset arrhythmias and unstable patients with atrial fibrillation, rate control strategies, the use of medical and direct current cardioversion for new-onset atrial fibrillation/atrial flutter, whom and when to anticoagulate, and the use of the novel anticoagulation agents.
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Atrial fibrillation is an abnormal heart rhythm affecting the upper chambers of the heart in which uncoordinated electrical depolarizations lead to ineffective contractions. Approximately five million patients in the US have atrial fibrillation, and this number is expected to double to 10 million over the next 30 years.1 Advancing age is a major risk factor for the development of atrial fibrillation; new cases of atrial fibrillation are diagnosed in men over age 80 at the rate of 2% per year.2 Although several drugs are available for management of atrial fibrillation, the efficacy of these drugs may be limited in elderly patients. In this review, we provide an overview of management of atrial fibrillation, with special emphasis on pharmacologic therapy versus arteriovenous (AV) node ablation in symptomatic elderly patients.
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This editorial introduces a series of review articles on different diagnostic modalities that can help to personalise the treatment of atrial fibrillation. The editorial outlines the current best evidence-based management of atrial fibrillation, and highlights the huge clinical need to improve outcomes in patients with atrial fibrillation further. It appears that understanding the causes of atrial fibrillation in individual patients would allow to design, test and validate better and personalised strategies for the treatment of this common threat to healthy ageing.
This issue of Heart inaugurates a series of review articles on atrial fibrillation. The reviews will explore different ways to apply existing diagnostic tests to personalise the management of patients with atrial fibrillation. Atrial fibrillation has received a lot of attention by researchers, clinicians, journals and the wider public in recent years, and there are good reasons to think and talk about this common arrhythmia: Assuming that the average reader of Heart is around 40 years old, every fourth of us will suffer from atrial fibrillation in his or her life.1 Those of us who will work in clinical medicine for another 20 years or 30 years will be faced with double or triple the amount of patients with atrial fibrillation that they see today.2 Furthermore, atrial fibrillation, while rarely acutely life-threatening, bears severe consequences for patients and societies: Atrial fibrillation causes …
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THE treatment of atrial fibrillation and the prevention of its complications are primarily pharmacologic problems. Treatment has two principal objectives. One is to use antiarrhythmic therapy to relieve symptoms; the other is to use prophylactic therapy to reduce the risk of stroke that accompanies atrial fibrillation. In planning the management of atrial fibrillation, it is useful to consider patients who are permanently in atrial fibrillation as having chronic atrial fibrillation and patients who have sinus rhythm punctuated by attacks of fibrillation as having paroxysmal atrial fibrillation. The two forms overlap, however, because many patients with chronic atrial fibrillation first present . . .
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The lecture presents modern concepts of diagnosis and treatment of atrial fibrillation; principles of choosing the tactics of management of atrial fibrillation in general practice. The epidemiology of atrial fibrillation, risk factors, causes and mechanisms of its development are considered. The classification of atrial fibrillation is given. The tactic of diagnosis of atrial fibrillation is described. The principles of treatment of atrial fibrillation, including the anticoagulant therapy and pharmacological cardioversion, are presented.
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Abstract Atrial fibrillation is the most common cardiac arrhythmia managed by emergency and acute general physicians. There is increasing evidence that selected patients with acute atrial fibrillation can be safely managed in the emergency department without the need for hospital admission. Meanwhile, there is significant variation in the current emergency management of acute atrial fibrillation. This review discusses evidence based emergency management of atrial fibrillation. The principles of emergency management of acute atrial fibrillation and the subset of patients who may not need hospital admission are reviewed. Finally, the need for evidence based guidelines before emergency department based clinical pathways for the management of acute atrial fibrillation becomes routine clinical practice is highlighted.
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Atrial fibrillation is the most common sustained disturbance of cardiac rhythm. It is a global epidemic and an evolving problem in cardiovascular medicine. Atrial fibrillation is an independent risk factor for embolic stroke, increasing the risk of stroke five-fold. Despite good evidence for the reduction of stroke risk with anticoagulant therapy, there is significant under treatment. Anticoagulant prescribing is frequently discordant with all current guidelines and decision aids with both over and under use of oral anticoagulants. It is important that GPs have up-to-date knowledge about atrial fibrillation in terms of both its diagnosis and management, and that patients have an understanding of anticoagulant medication. This article aims to update knowledge about atrial fibrillation, the use and benefits of anticoagulation with insights on some barriers to anticoagulation in primary care. This article does not cover management of atrial fibrillation with control of cardiac rate or rhythm to maintain cardiac function.
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