Rate Control in Atrial Fibrillation
2015; Lippincott Williams & Wilkins; Volume: 132; Issue: 17 Linguagem: Italiano
10.1161/circulationaha.115.018952
ISSN1524-4539
AutoresIsabelle C. Van Gelder, Anne H. Hobbelt, Bart A. Mulder, Michiel Rienstra,
Tópico(s)Cardiac Arrhythmias and Treatments
ResumoHomeCirculationVol. 132, No. 17Rate Control in Atrial Fibrillation Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBRate Control in Atrial FibrillationMany Questions Still Unanswered Isabelle C. Van Gelder, MD, PhD, Anne H. Hobbelt, MD, Bart A. Mulder, MD, PhD and Michiel Rienstra, MD, PhD Isabelle C. Van GelderIsabelle C. Van Gelder From Department of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, The Netherlands. , Anne H. HobbeltAnne H. Hobbelt From Department of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, The Netherlands. , Bart A. MulderBart A. Mulder From Department of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, The Netherlands. and Michiel RienstraMichiel Rienstra From Department of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, The Netherlands. Originally published17 Sep 2015https://doi.org/10.1161/CIRCULATIONAHA.115.018952Circulation. 2015;132:1597–1599Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 27, 2015: Previous Version 1 More than 10 years ago, 7 rate versus rhythm control trials demonstrated that, in patients with paroxysmal and persistent atrial fibrillation (AF), rate control was comparable to rhythm control regarding outcome.1,2 From that moment on, rate control became frontline therapy in older patients with few or acceptable symptoms of AF. Although rate control was an easy-to-perform therapeutic strategy, rate control criteria, and the selection of drugs, as well, were not evidence based. It is interesting that, in the rate versus rhythm control trials, rate-controlling strategies differed significantly. Whereas the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial aimed to achieve heart rates comparable to the heart rates during sinus rhythm, patients included in the Rate Control versus Electric cardioversion for Persistent Atrial Fibrillation (RACE) study were treated with a more lenient approach. Thus far, only 1 randomized clinical trial has been performed evaluating different rate control strategies. The Rate Control Efficacy in Permanent Atrial Fibrillation: a comparison between Lenient and Strict Rate Control II (RACE II) study compared a strict rate control approach with a more lenient rate control approach in patients with permanent AF.3,4 The RACE II trial showed that a lenient rate control approach was not inferior in comparison with a strict rate control approach regarding cardiovascular morbidity and mortality in patients with permanent AF without severe heart failure (HF). Subsequently, the American College of Cardiology, American Heart Association, Heart Rhythm Society, and European Society of Cardiology guidelines adopted a lenient rate control approach as initial strategy in asymptomatic patients as long as the left ventricular function remains preserved.5,6 A more strict rate control approach, however, was recommended in more symptomatic patients or when left ventricular function deteriorates.Article see p 1604No recommendation can be provided regarding the choice of negative dromotropic drug. Randomized long-term trials with cardiovascular morbidity and mortality as the primary end points have not been executed. In general, β-blockers and calcium channel blockers are often instituted, alone or in combination, depending on the type and severity of associated diseases and patient's physical lifestyle.In the current issue of Circulation, Chao et al7 describe the outcome in patients with AF treated with either a β-blocker, a calcium channel blocker, or digoxin as the sole rate control drug in a large Taiwanese nationwide AF cohort. They used the National Health Insurance Research Database that consists of detailed healthcare data from >23 million enrollees, representing >99% of Taiwan's population. It is important that patients were included when only one of these drugs was instituted; patients with combinations of rate control drugs were excluded. A total of 43 879, 18 466, and 38 898 patients were enrolled in the β-blocker, calcium channel blocker, and digoxin groups, respectively. Each group was compared with a reference group of AF patients who were not treated with any rate control drug. Reasons for no rate-controlling treatment were not provided. During a follow-up of 4.9±3.7 years, mortality occurred in 32.7%. After adjustment for baseline differences, which were significant between the respective groups, the risk of mortality was lower in patients receiving β-blockers (adjusted hazard ratio, 0.76; 95% confidence interval, 0.74–0.78; P<0.001) and calcium channel blockers (adjusted hazard ratio, 0.93; 95% confidence interval, 0.90–0.96; P<0.001) in comparison with those who did not receive rate control medications. In contrast, the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 (95% confidence interval, 1.10–1.14; P<0.001) in comparison with to their reference group. These differences between each rate control drug and its respective reference group were confirmed by using propensity-matched analyses. From these analyses, the authors conclude that (1) β-blockers were associated with the largest risk reduction in mortality; (2) the same was observed for calcium channel blockers, albeit with a lower significance; whereas (3) digoxin was associated with an increased mortality rate.The authors are congratulated for their work, which contributes to our knowledge on standard care in every AF patient, namely rate control. They included a large number of AF patients recruited from a nationwide Taiwanese Health Insurance database. First, it is relevant that these data come from Asian AF patients, contrary to previous reports on rate-controlling drugs predominantly including white patients. This may be reflected by the high previous stroke rate in up to one-third of the patients included. Interestingly, despite the high previous stroke rate, the use of oral anticoagulation was low. Second, they observed differences in outcome between rate control drugs. These differences were identified after comparison of each (nonrandomized) rate control drug with their respective reference group of patients who were not treated with any rate control drug. Unfortunately, the information on why the reference group was not treated with rate control drugs and the actual heart rates in all groups were not provided. Also missing were data on dosages of the instituted rate-controlling drugs. Because of these important limitations, the results should be considered as hypothesis generating, warranting confirmation by randomized trials.For now, what can we learn? Let us first focus on β-blockers. The present data regarding β-blockers in AF are more favorable than the outcomes of studies analyzing AF patients with HF with a reduced ejection fraction (HFREF) and HF with a preserved ejection fraction. In contrast to patients with HFREF or HF with a preserved ejection fraction in sinus rhythm, AF patients with HF do not seem to benefit from β-blockers.8–10 Only 1 other analysis has shown, like the present data, a beneficial effect of β-blocker therapy in AF.11 A Swedish registry in patients with HF with a preserved ejection fraction showed that the use of β-blockers was associated with lower all-cause mortality. Subgroup analysis revealed that the benefits of β-blockers were only observed for AF patients.11 Thus, β-blockers are an effective means of controlling the ventricular rate in patients with AF, both with and without HF. A harmful effect has never been described. Whether these drugs are able to reduce mortality in AF patients remains to be investigated in well-designed randomized trials.Second, not a lot of data are available on calcium channel blockers, with the exception that they are contraindicated in HFREF patients. Only recently, the beneficial effects of calcium channel blockers have been suggested by a small-scale randomized trial by Ulimoen et al.12–14 The Rate Control in Atrial Fibrillation (RATAF) study was a prospective, randomized, investigator-blinded crossover study designed to compare 4 drug regimens: metoprolol slow-release tablets 100 mg/d, diltiazem sustained-release capsules 360 mg/d, verapamil modified-release tablets 240 mg/d, and carvedilol immediate-release tablets 25 mg/d. Each drug was given for a period of 3 weeks in 60 AF patients with permanent AF without HFREF. Diltiazem was the most effective drug regimen for reducing the ventricular rate. Arrhythmia-related symptoms were reduced by treatment with both calcium channel blockers, diltiazem and verapamil, but not by β-blockers.12–14 Diltiazem and verapamil also preserved exercise capacity and reduced levels of N-terminal pro-brain natriuretic peptide, whereas treatment with metoprolol or carvedilol reduced the exercise capacity and increased levels of N-terminal pro-brain natriuretic peptide. Therefore, nondihydropyridine calcium channel blockers are useful to control the ventricular rate during AF, albeit only in patients without HFREF.Finally, the detrimental effects of digoxin. At present, the use of digoxin has declined, most importantly because there is no evidence that digoxin is an effective rate control drug during exercise, but only during rest.15 Data on cardiovascular outcomes from patients with AF who used digoxin were predominantly derived from post hoc analyses from the AFFIRM. An early report on predictors for mortality in the AFFIRM trial reported that digoxin was independently associated with increased mortality in patients with AF.16 More recently, 2 additional post hoc analyses of AFFIRM on the effect of digoxin were conducted and reported conflicting results of its effect on prognosis.17,18 Additional data have been published. A recent meta-analysis confirmed that digoxin is associated with an increased mortality risk, especially in patients with AF.19 However, neutral effects also were observed. Data from the RACE II trial showed that, in patients with permanent AF, digoxin use was not associated with an impaired outcome.20 Differences observed between analyses may be related to differences in the type of AF, dosages, comorbidities, and concomitant medications.21,22 Therefore, digoxin is useful in selected patients, but should be instituted carefully.Our take-home messages are: (1) Rate control institution in patients with AF is aimed to control the ventricular heart rate. Lenient rate control can be a first-choice strategy in patients with no or minor symptoms. A more strict rate control approach should be adopted when symptoms persist or deterioration of the left ventricular function occurs. (2) A second aim is to institute drugs that may improve outcome in AF patients. The present study adds to the overwhelming and often inconsistent data on the beneficial or detrimental effects of the different rate-controlling drugs. (3) Until data from randomized trials are available, we stress that the choice of rate control drugs should be individualized depending on age, lifestyle, associated comorbidities, and heart rate. (4) Finally, rate control drugs should be instituted carefully, and dosages may be adopted during the course of the disease because comorbidities and conduction disturbances may either develop or proceed. Clearly, there is much to learn about rate control in AF.Sources of FundingDr Rienstra is supported by grants from the Netherlands Organization for Scientific Research (Veni grant 016.136.055) and from the EHRA Academic Fellowship Program.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Isabelle C. van Gelder, MD, PhD, Department of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. 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Seecheran R, Narayansingh R, Giddings S, Rampaul M, Furlonge K, Abdool K, Bhagwandass N and Seecheran N (2020) Atrial Arrhythmias in a Patient Presenting With Coronavirus Disease-2019 (COVID-19) Infection, Journal of Investigative Medicine High Impact Case Reports, 10.1177/2324709620925571, 8, (232470962092557), Online publication date: 1-Jan-2020. Rogge C, Hilbert S, Dagres N and Hindricks G (2016) Aktueller Stand der Differenzialtherapie des VorhofflimmernsCurrent state of treatment strategies for atrial fibrillation, Herz, 10.1007/s00059-016-4413-9, 41:3, (253-270), Online publication date: 1-May-2016. Lip G, Fauchier L, Freedman S, Van Gelder I, Natale A, Gianni C, Nattel S, Potpara T, Rienstra M, Tse H and Lane D (2016) Atrial fibrillation, Nature Reviews Disease Primers, 10.1038/nrdp.2016.16, 2:1, Online publication date: 22-Dec-2016. October 27, 2015Vol 132, Issue 17 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.115.018952PMID: 26384161 Originally publishedSeptember 17, 2015 KeywordsmortalityEditorialsdigoxinβ-blockerheart ratePDF download Advertisement SubjectsAtrial Fibrillation
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