Rate control strategies for atrial fibrillation.
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ABSTRACT:
SUBMITTER: Alobaida M
PROVIDER: S-EPMC8158272 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionAtrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (<110 beats per minute (bpm) at rest) compared with strict rate control strategy (<80 bpm at rest) on quality of life in patients with persistent or permanent atrial fibrillation.Methods and analysisWe plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (<110 bpm at rest) or a strict medical rate control strategy (<80 bpm at rest). The recruitment phase is planned to be 2 years with 3 years of follow-up. Recruitment is expected to start in January 2021. The primary outcome will be quality of life using the Short Form-36 (SF-36) questionnaire (physical component score). Secondary outcomes will be days alive outside hospital, symptom control using the Atrial Fibrillation Effect on Quality of Life, quality of life using the SF-36 questionnaire (mental component score) and serious adverse events. The primary assessment time point for all outcomes will be 1 year after randomisation.Ethics and disseminationEthics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov.Trial registration numberNCT04542785.
| S-EPMC8016086 | biostudies-literature
Project description:BACKGROUND:Atrial fibrillation and atrial flutter may be managed by either a rhythm control strategy or a rate control strategy but the evidence on the clinical effects of these two intervention strategies is unclear. Our objective was to assess the beneficial and harmful effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter. METHODS:We searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, BIOSIS, Google Scholar, clinicaltrials.gov, TRIP, EU-CTR, Chi-CTR, and ICTRP for eligible trials comparing any rhythm control strategy with any rate control strategy in patients with atrial fibrillation or atrial flutter published before November 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were stroke and ejection fraction. We performed both random-effects and fixed-effect meta-analysis and chose the most conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. Statistical heterogeneity was assessed by visual inspection of forest plots and by calculating inconsistency (I2) for traditional meta-analyses and diversity (D2) for TSA. Sensitivity analyses and subgroup analyses were conducted to explore the reasons for substantial statistical heterogeneity. We assessed the risk of publication bias in meta-analyses consisting of 10 trials or more with tests for funnel plot asymmetry. We used GRADE to assess the quality of the body of evidence. RESULTS:25 randomized clinical trials (n = 9354 participants) were included, all of which were at high risk of bias. Meta-analysis showed that rhythm control strategies versus rate control strategies significantly increased the risk of a serious adverse event (risk ratio (RR), 1.10; 95% confidence interval (CI), 1.02 to 1.18; P = 0.02; I2 = 12% (95% CI 0.00 to 0.32); 21 trials), but TSA did not confirm this result (TSA-adjusted CI 0.99 to 1.22). The increased risk of a serious adverse event did not seem to be caused by any single component of the composite outcome. Meta-analysis showed that rhythm control strategies versus rate control strategies were associated with better SF-36 physical component score (mean difference (MD), 6.93 points; 95% CI, 2.25 to 11.61; P = 0.004; I2 = 95% (95% CI 0.94 to 0.96); 8 trials) and ejection fraction (MD, 4.20%; 95% CI, 0.54 to 7.87; P = 0.02; I2 = 79% (95% CI 0.69 to 0.85); 7 trials), but TSA did not confirm these results. Both meta-analysis and TSA showed no significant differences on all-cause mortality, SF-36 mental component score, Minnesota Living with Heart Failure Questionnaire, and stroke. CONCLUSIONS:Rhythm control strategies compared with rate control strategies seem to significantly increase the risk of a serious adverse event in patients with atrial fibrillation. Based on current evidence, it seems that most patients with atrial fibrillation should be treated with a rate control strategy unless there are specific reasons (e.g., patients with unbearable symptoms due to atrial fibrillation or patients who are hemodynamically unstable due to atrial fibrillation) justifying a rhythm control strategy. More randomized trials at low risk of bias and low risk of random errors are needed. TRIAL REGISTRATION:PROSPERO CRD42016051433.
| S-EPMC5658096 | biostudies-literature
Project description:BACKGROUND:Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS:Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS:Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS:Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).
| S-EPMC4908812 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice, which is associated with substantial risk of stroke and thromboembolism. As an arrhythmia that is particularly common in the elderly, it is an important contributor towards morbidity and mortality. Ventricular rate control has been a preferred and therapeutically convenient treatment strategy for the management of AF. Recent research in the field of rhythm control has led to the advent of newer antiarrhythmic drugs and catheter ablation techniques as newer therapeutic options. Currently available antiarrhythmic drugs still remain limited by their suboptimal efficacy and significant adverse effects. Catheter ablation as a newer modality to achieve sinus rhythm (SR) continues to evolve, but data on long-term outcomes on its efficacy and mortality outcomes are not yet available. Despite these current developments, rate control continues to be the front-line treatment strategy, especially in older and minimally symptomatic patients who might not tolerate the antiarrhythmic drug treatment. This review article discusses the current evidence and recommendations for ventricular rate control in the management of AF. We also highlight the considerations for rhythm control strategy in the management of patients of AF.
| S-EPMC4711525 | biostudies-other
Project description:Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies.The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes.Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA?DS?-VASc score 2.4±1.5 vs. 3.1±1.7, p<0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment.In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.
| S-EPMC5823828 | biostudies-literature
Project description:Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment. Because If channels were thought to be expressed solely in sinoatrial (SA) nodal tissue, ivabradine was not investigated in heart failure patients with concomitant AF. Subsequent identification of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4), the primary gene responsible for If current expression throughout the myocardium, stimulated interest in the potential role of ivabradine for ventricular rate control in AF. Preclinical studies of ivabradine in animal models with induced AF demonstrated a reduction in HR, with no significant worsening of QT interval or mean arterial pressure. Preliminary human data suggest that ivabradine provides HR reduction without associated hemodynamic complications in patients with AF. Questions remain regarding efficacy, safety, optimal dosing, and length of therapy in these patients. Prospective, randomized studies are needed to determine if ivabradine has a role as a rate-control treatment in patients with AF.
| S-EPMC5933550 | biostudies-literature
Project description:BackgroundThe relationship between the ventricular rate (VR) during atrial fibrillation (AF) and skin sympathetic nerve activity (SKNA) remains unclear.ObjectiveThe purpose of this study was to test the hypothesis that SKNA bursts accelerate VR during AF.MethodsWe simultaneously recorded electrocardiogram and SKNA in 8 patients (median age 66.0 years [interquartile range {IQR} 59.0-77.0 years]; 4 men [50%]) with 30 paroxysmal AF episodes (all >10-minute long) and 12 patients (73.0 years [IQR 60.5-80.0 years]; 6 men [50%]) with persistent AF. The average amplitude of SKNA (aSKNA [μV]) during AF was analyzed in 1-minute windows and binned, showing 2 Gaussian distributions. We used the mean + 3SD of the first Gaussian distribution as the threshold that separates burst from baseline (nonburst) SKNA. All 1-minute aSKNA values above the threshold were detected, and the area between aSKNA and baseline of every 1 minute was calculated and added as burst area.ResultsVR was higher during SKNA bursts than during the nonburst period (103 beats/min [IQR 83-113 beats/min] vs 88 beats/min [IQR 76-101 beats/min], respectively; P = .003). In the highest quartile of the burst area during persistent AF, the scatterplot of maximal aSKNA and VR during each SKNA burst shows higher aSKNA and VR. The overall estimate of the correlation between maximal VR and aSKNA during bursts show a positive correlation in the highest quartile of the burst area (0.64; 95% confidence interval 0.54-0.74; P < .0001).ConclusionSKNA bursts are associated with VR acceleration. These SKNA bursts may be new therapeutic targets for rate control during AF.
| S-EPMC7117970 | biostudies-literature
Project description:BACKGROUND:Detectable levels of troponins are often found in serum of patients with atrial fibrillation (AF), and recent reports suggest that Tn concentrations are independently related to patient prognosis. HYPOTHESIS:We hypothesized that treatment with common rate-reducing drugs might lower the levels of cardiac troponin T (TnT) in patients with permanent AF. We also wanted to investigate whether the different drugs would impact the Tn levels differently. METHODS:Sixty patients were included (mean age 71 ± 9 years, 18 women) in this randomized crossover study. All patients had stable, permanent AF without ischemic heart disease or congestive heart failure. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for 3 weeks, in a randomized sequence. At baseline and on the last day of each treatment period, TnT concentrations were measured at rest and after a maximal exercise test. RESULTS:TnT was detectable in all patients. In 22% of the patients, TnT concentrations were above the threshold normally used for diagnosing myocardial infarction. All drugs reduced the levels of TnT significantly compared with baseline (P < 0.001 for all), but there were no significant differences between the treatments. Levels of TnT increased significantly in response to exercise testing (P < 0.001 for all). CONCLUSIONS:Elevated TnT was demonstrated in a large proportion of stable patients with permanent AF without ischemic heart disease. A moderate reduction of heart rate by the study drugs was associated with a significant reduction in levels of TnT.
| S-EPMC6649449 | biostudies-literature
Project description:AimsWe hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control.Methods and resultsIn this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93).ConclusionIn patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control.
| S-EPMC8892061 | biostudies-literature
Project description:Given the sparse evidence for selection of first-line therapy for acute atrial fibrillation (AF) based on clinical factors alone, incorporation of genotype data may improve the effectiveness of treatment algorithms and advance the understanding of interpatient heterogeneity. We tested whether candidate nucleotide polymorphisms (SNPs) related to AF physiologic responses are associated with ventricular rate control after intravenous diltiazem in the emergency department (ED).We conducted an analysis within a prospective observational cohort of ED patients with acute symptomatic AF, ventricular rate >110 beats per minute within the first 2 hours, initially treated with intravenous diltiazem, and who had DNA available for analysis. We evaluated 24 candidate SNPs that were grouped into 3 categories based on their phenotype response (atrioventricular nodal [AVN] conduction, resting heart rate, disease susceptibility) and calculated 3 genetic scores for each patient. Our primary outcome was maximum heart rate reduction within 4 hours of diltiazem administration. Multivariable regression was used to identify associations with the outcome while adjusting for age, sex, baseline heart rate, and diltiazem dose.Of the 142 patients, 127 had complete data for the primary outcome. None of the genetic scores for AVN conduction, resting heart rate, or AF susceptibility showed a significant association with maximal heart rate response.Using a candidate SNP approach, screening for genetic variants associated with AVN conduction, resting heart rate, or AF susceptibility failed to provide significant data for predicting successful rate control response to intravenous diltiazem for treating acute AF in the ED.
| S-EPMC4801711 | biostudies-literature