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F1000Research 2017Previous randomized trials on patent foramen ovale (PFO) closure versus medical therapy for stroke prevention were inconclusive. Recently, two new randomized trials and...
Previous randomized trials on patent foramen ovale (PFO) closure versus medical therapy for stroke prevention were inconclusive. Recently, two new randomized trials and new findings from an extended follow-up of a previous trial have been published on this topic. We conducted a systematic review and meta-analysis of randomized trials comparing PFO closure with medical therapy for stroke prevention. PubMed and Cochrane Library were searched until 16 September 2017. The following search terms were used for PubMed: "patent foramen ovale" AND (stroke OR embolism) and "randomized" AND "Trial". For Cochrane Library, the following terms were used: "patent foramen ovale" AND "closure" AND (stroke OR embolism). A total of 91 and 55 entries were retrieved from each database using our search strategy respectively, of which six studies on five trials met the inclusion criteria. This meta-analysis included 1829 patients in the PFO closure arm (mean age: 45.3 years; 54% male) and 1972 patients in the medical therapy arm (mean age: 45.1 years; 51% male). The median follow-up duration was 50 ± 30 months. When compared to medical therapy, PFO closure significantly reduced primary endpoint events with a risk ratio [RR] of 0.60 (95% CI: 0.44-0.83, P < 0.0001; : 15%). It also reduced stroke (RR: 0.50, 95% CI: 0.35-0.73, P < 0.0001; : 32%) despite increasing the risk of atrial fibrillation/flutter (RR: 1.90, 95% CI: 1.23-2.93, P < 0.01; : 43%). However, it did not reduce transient ischemic accident events (0.75; 95% CI: 0.51-1.10, P = 0.14; : 0%), all-cause bleeding (RR: 0.89; 95% CI: 0.44-1.78, P = 0.74; : 51%) or gastrointestinal complications (RR: 0.92; 95% CI: 0.32-2.70, P = 0.88; : 0%). PFO closure significantly reduces risk of stroke when compared to medical treatment and should therefore be considered for stroke prevention in PFO patients.
PubMed: 30271571
DOI: 10.12688/f1000research.13444.2 -
JACC. Clinical Electrophysiology Jul 2018This analysis sought to systematically characterize trial-level patterns in atrial fibrillation/atrial flutter (AF/AFL) by using the ClinicalTrials.gov database.
OBJECTIVES
This analysis sought to systematically characterize trial-level patterns in atrial fibrillation/atrial flutter (AF/AFL) by using the ClinicalTrials.gov database.
BACKGROUND
Despite an abundance of clinical trials in this field, there is a lack of high-level evidence guiding management of AF/AFL.
METHODS
We queried all closed, phase II to IV interventional trials registered in the ClinicalTrials.gov database through October 2016 that enrolled patients known to have AF/AFL. Published trials were evaluated for methodological quality, using the 3-item Jadad scale (range: 0 to 5, where 5 = highest quality).
RESULTS
The initial search yielded 465 uniquely registered studies, of which 348 directly studied AF/AFL. Of those studies, 173 (50%) were published, enrolling a median of 190 patients from a median of 15 sites. The volume of published trials increased over time (7% prior to 2008 vs. 41% from 2014 to 2016; p < 0.001 for trend). Of the completed trials, 29% remain unpublished. Industry sources accounted for most funding (54%). Recurrence of AF/AFL was the most common endpoint (45%), whereas rates of primary clinical endpoints were low (13%). The mean Jadad score of published trials of pharmacological approaches (n = 112) was 4.0 ± 1.4. Of the 61 AF/AFL trials involving ablation or device therapies, 69% were randomized, 28% were single-arm studies, and patient, proceduralist, and event-ascertainment blinding was used in 16%, 4%, and 44%, respectively.
CONCLUSIONS
Contemporary trials of AF/AFL are often multicenter and modest in size. The primary study endpoint is commonly recurrence of arrhythmia, even in high-quality and late-phase trials. Although methodological quality is high in trials of pharmacologic approaches, trials of AF/AFL ablation and device therapies variably employ randomization and blinding.
Topics: Atrial Fibrillation; Atrial Flutter; Clinical Trials as Topic; Humans; Practice Guidelines as Topic
PubMed: 30025696
DOI: 10.1016/j.jacep.2018.04.008 -
PLoS Neglected Tropical Diseases Jun 2018Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population.
METHODS
Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model.
RESULTS
Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants.
CONCLUSIONS
This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.
Topics: Adult; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Chagas Disease; Child; Electrocardiography; Female; Heart Conduction System; Humans; Male; Observational Studies as Topic; Odds Ratio; Prevalence
PubMed: 29897909
DOI: 10.1371/journal.pntd.0006567 -
PloS One 2018During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence.
RESULTS
28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%).
CONCLUSIONS
The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42016052935.
Topics: Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Bias; Calcium Channel Blockers; Comorbidity; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Mortality; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Stroke; Treatment Outcome
PubMed: 29518134
DOI: 10.1371/journal.pone.0193924 -
BMC Cardiovascular Disorders Mar 2018Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cryptogenic stroke. However, the comparative efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cryptogenic stroke. However, the comparative efficacy and safety of percutaneous closure and medical therapy in patients with cryptogenic stroke and PFO remain unclear.
METHODS
Randomized controlled trials (RCTs) and comparative observational studies that compared PFO closure against medical therapy, each with a minimal of 20 patients in the closure arm and 1-year follow-up were included.
RESULTS
We analyzed 6961 patients from 20 studies (5 RCTs and 15 observational studies) with a median follow-up of 3.1 years. Moderate-quality evidence showed that PFO closure was associated with a significantly lower incidence of the composite outcome of ischemic stroke, transient ischemic attack (TIA), or all-cause death (odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.38 to 0.85; P = 0.006), mainly driven by lower incidence of stroke (OR: 0.39; 95% CI: 0.24 to 0.63; P < 0.001). The numbers needed to treat were 43 and 39 for the composite outcome and recurrent ischemic stroke respectively. PFO closure increased the risks for atrial fibrillation or atrial flutter (OR: 5.74; 95% CI: 3.08 to 10.70; P < 0.001; high-quality evidence) and pulmonary embolism (OR: 3.03; 95% CI: 1.06 to 8.63; P = 0.038; moderate-quality evidence), with the numbers needed to harm being 30 and 143 respectively. The risks for TIA, all-cause death, and major bleeding were not statistically different. Analyses limited to RCTs showed similar findings, as did a series of other subgroup analyses.
CONCLUSION
In conclusion, PFO closure reduced the incidences of stroke and the composite outcome of ischemic stroke, TIA, or all-cause death, but increased risks for atrial fibrillation or atrial flutter and pulmonary embolism compared with medical therapy.
Topics: Adult; Atrial Fibrillation; Atrial Flutter; Cardiac Catheterization; Cardiovascular Agents; Female; Foramen Ovale, Patent; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Observational Studies as Topic; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Time Factors; Treatment Outcome
PubMed: 29499641
DOI: 10.1186/s12872-018-0780-x -
Journal of the American Heart... Dec 2017There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta-analysis was to compare the efficacy, safety, and fetal-maternal tolerance of first-line monotherapies for fetal supraventricular tachycardia and atrial flutter.
METHODS AND RESULTS
A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first-line treatments of fetal tachyarrhythmia were included. Outcomes of interest were termination of fetal tachyarrhythmia, fetal demise, and maternal complications. Ten studies met inclusion criteria, with 537 patients. Overall, 291 patients were treated with digoxin, 137 with flecainide, 102 with sotalol, and 7 with amiodarone. Digoxin achieved a lower rate of supraventricular tachycardia termination compared with flecainide (odds ratio [OR]: 0.773; 95% confidence interval [CI], 0.605-0.987; I=34%). In fetuses with hydrops fetalis, digoxin had lower rates of tachycardia termination compared with flecainide (OR: 0.412; 95% CI, 0.268-0.632; I=0%). There was no significant difference in the incidence of maternal side effects between digoxin and flecainide groups (OR: 1.134; 95% CI, 0.129-9.935; I=80.79%). The incidence of maternal side effects was higher in patients treated with digoxin compared with sotalol (OR: 3.148; 95% CI, 1.468-6.751; I=0%). There was no difference in fetal demise between flecainide and digoxin (OR: 0.767; 95% CI, 0.140-4.197; I=44%).
CONCLUSIONS
Flecainide may be more effective treatment than digoxin as a first-line treatment for fetal supraventricular tachycardia.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Echocardiography; Female; Fetal Diseases; Fetal Therapies; Flecainide; Humans; Pregnancy; Prenatal Care; Prenatal Diagnosis
PubMed: 29246961
DOI: 10.1161/JAHA.117.007164 -
The American Journal of Medicine May 2018Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and follow-up.
METHODS
We conducted a systematic search of published randomized clinical trials evaluating patent foramen ovale closure versus medical therapy in patients with recent stroke or transient ischemic attack using PubMED, EMBASE, and Cochrane through September 2017. Weighting was by random effects models.
RESULTS
Of 480 studies screened, we included 5 randomized clinical trials in the meta-analysis in which 3440 patients were randomized to patent foramen ovale closure (n = 1829) or medical therapy (n = 1611) and followed for an average of 2.0 to 5.9 years. Index stroke/transient ischemic attack occurred within 6 to 9 months of randomization. The primary end point was composite stroke/transient ischemic attack and death (in 3 trials) or stroke alone (in 2 trials). Patent foramen ovale closure reduced the primary end point (0.70 vs 1.48 events per 100 patient-years; risk ratio [RR], 0.52 [0.29-0.91]; I = 55.0%) and stroke/transient ischemic attack (1.04 vs 2.00 events per 100 patient-years; RR, 0.55 [0.37-0.82]; I = 42.2%) with modest heterogeneity compared with medical therapy. Procedural bleeding was not different between study arms (1.8% vs 1.8%; RR, 0.94 [0.49-1.83]; I = 29.2%), but new-onset atrial fibrillation/flutter was increased with patent foramen ovale closure (6.6% vs 0.7%; RR, 4.69 [2.17-10.12]; I = 29.3%).
CONCLUSIONS
In patients with recent cryptogenic stroke, patent foramen ovale closure reduces recurrent stroke/transient ischemic attack compared with medical therapy, but is associated with a higher risk of new-onset atrial fibrillation/flutter.
Topics: Anticoagulants; Atrial Fibrillation; Atrial Flutter; Foramen Ovale, Patent; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 29229471
DOI: 10.1016/j.amjmed.2017.11.027 -
The Cochrane Database of Systematic... Nov 2017Atrial fibrillation is the commonest cardiac dysrhythmia. It is associated with significant morbidity and mortality. There are two approaches to the management of atrial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation is the commonest cardiac dysrhythmia. It is associated with significant morbidity and mortality. There are two approaches to the management of atrial fibrillation: controlling the ventricular rate or converting to sinus rhythm in the expectation that this would abolish its adverse effects.
OBJECTIVES
To assess the effects of pharmacological cardioversion of atrial fibrillation in adults on the annual risk of stroke, peripheral embolism, and mortality.
SEARCH METHODS
We searched the Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (2000 to 2002), EMBASE (1998 to 2002), CINAHL (1982 to 2002), Web of Science (1981 to 2002). We hand searched the following journals: Circulation (1997 to 2002), Heart (1997 to 2002), European Heart Journal (1997-2002), Journal of the American College of Cardiology (1997-2002) and selected abstracts published on the web site of the North American Society of Pacing and Electrophysiology (2001, 2002).
SELECTION CRITERIA
Randomised controlled trials or controlled clinical trials of pharmacological cardioversion versus rate control in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and of any aetiology.
DATA COLLECTION AND ANALYSIS
One reviewer applied the inclusion criteria and extracted the data. Trial quality was assessed and the data were entered into RevMan.
MAIN RESULTS
We identified two completed studies AFFIRM (n=4060) and PIAF (n=252). We found no difference in mortality between rhythm control and rate control relative risk 1.14 (95% confidence interval 1.00 to 1.31).Both studies show significantly higher rates of hospitalisation and adverse events in the rhythm control group and no difference in quality of life between the two treatment groups.In AFFIRM there was a similar incidence of ischaemic stroke, bleeding and systemic embolism in the two groups. Certain malignant dysrhythmias were significantly more likely to occur in the rhythm control group. There were similar scores of cognitive assessment.In PIAF, cardioverted patients enjoyed an improved exercise tolerance but there was no overall benefit in terms of symptom control or quality of life.
AUTHORS' CONCLUSIONS
There is no evidence that pharmacological cardioversion of atrial fibrillation to sinus rhythm is superior to rate control. Rhythm control is associated with more adverse effects and increased hospitalisation. It does not reduce the risk of stroke. The conclusions cannot be generalised to all people with atrial fibrillation. Most of the patients included in these studies were relatively older (>60 years) with significant cardiovascular risk factors.
Topics: Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Heart Rate; Humans; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 29140557
DOI: 10.1002/14651858.CD003713.pub3 -
The Cochrane Database of Systematic... Nov 2017Atrial fibrillation increases stroke risk and adversely affects cardiovascular haemodynamics. Electrical cardioversion may, by restoring sinus rhythm, improve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation increases stroke risk and adversely affects cardiovascular haemodynamics. Electrical cardioversion may, by restoring sinus rhythm, improve cardiovascular haemodynamics, reduce the risk of stroke, and obviate the need for long-term anticoagulation.
OBJECTIVES
To assess the effects of electrical cardioversion of atrial fibrillation or flutter on the risk of thromboembolic events, strokes and mortality (primary outcomes), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcomes) in adults (>18 years).
SEARCH METHODS
We searched the Cochrane CENTRAL Register of Controlled Trials (1967 to May 2004), MEDLINE (1966 to May 2004), Embase (1980 to May 2004), CINAHL (1982 to May 2004), proceedings of the American College of Cardiology (published in Journal of the American College of Cardiology 1983 to 2003), www.trialscentral.org, www.controlled-trials.com and reference lists of articles. We hand-searched the indexes of the Proceedings of the British Cardiac Society published in British Heart Journal (1980 to 1995) and in Heart (1995 to 2002); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2003); scientific sessions of the American Heart Association (published in Circulation 1990-2003). Personal contact was made with experts.
SELECTION CRITERIA
Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of anticoagulants, antiplatelet drugs and drugs for 'rate control'. We excluded trials which used pharmacological cardioversion as the first intervention, and trials of new onset atrial fibrillation after cardiac surgery. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
For dichotomous data, odds ratios were calculated; and for continuous data, the weighted mean difference was calculated.
MAIN RESULTS
We found three completed trials of electrical cardioversion (rhythm control) versus rate control, recruiting a total of 927 participants (Hot Cafe; RACE; STAF) and one ongoing trial (J-RHYTHM). There was no difference in mortality between the two strategies (OR 0.83; CI 0.48 to 1.43). There was a trend towards more strokes in the rhythm control group (OR 1.9; 95% CI 0.99 to 3.64). At follow up, three domains of quality of life (physical functioning, physical role function and vitality) were significantly better in the rhythm control group (RACE 2002; STAF 2003).
AUTHORS' CONCLUSIONS
Electrical cardioversion (rhythm control) led to a non-significant increase in stroke risk but improved three domains of quality of life.
Topics: Adult; Atrial Fibrillation; Atrial Flutter; Electric Countershock; Humans; Randomized Controlled Trials as Topic
PubMed: 29140555
DOI: 10.1002/14651858.CD002903.pub3 -
PloS One 2017Atrial 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... (Meta-Analysis)
Meta-Analysis Review
The effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and Trial Sequential Analysis.
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.
Topics: Atrial Fibrillation; Atrial Flutter; Cause of Death; Humans; Quality of Life
PubMed: 29073191
DOI: 10.1371/journal.pone.0186856