Key Messages
- Electrical cardioversion and some drugs can be used to restore the normal rhythm in patients with atrial fibrillation (AF) and atrial flutter. While electrical cardioversion is highly effective in dealing with all arrhythmias, the efficacy of drugs varies, with some being only moderately effective or not working at all in persistent AF and atrial flutter.
- Electrical cardioversion seems to be a very safe option. The risk of severe complications with cardioversion using drugs was low, but additional precautions are needed.
‐ We need further studies to find out if these treatment options also have a positive effect on quality of life, or if they lead to relevant differences in the duration of hospital stay.
What is atrial fibrillation?
AF is the most frequent abnormal heart rhythm seen in the world. Patients with this condition may feel their heart beating rapidly and irregularly. This can occur for separate brief or long episodes (paroxysmal AF) or it may become continuous (persistent AF). Atrial flutter is a similar abnormal rhythm that causes similar symptoms, can cause episodes of variable duration and can also become continuous.
What is cardioversion?
Cardioversion is a treatment to restore the rhythm of the heart back to normal (sinus rhythm).
What did we want to find out?
We wanted to know if delivering a controlled electrical shock (i.e. electrical cardioversion) and drugs (i.e. pharmacological cardioversion) are effective and safe when restoring heart rhythm back to normal.
What did we do?
We searched for studies that investigated electrical and pharmacological cardioversion compared to each other or placebo (a medicine that looks like the real medicine but that has no active ingredient).
We compared and summarised the results of the studies and rated our trust in these results, based on factors such as study methods and size.
What did we find?
We found 112 studies. We were able to combine and analyse the results from 72 studies, with 15,968 participants aged between 47 and 72 years. Thirty-five studies included patients with paroxysmal AF (AF that terminates spontaneously or with intervention within 7 days of onset), 26 studies of patients with persistent AF (AF that is continuously sustained beyond seven days, including episodes terminated by cardioversion after ≥ 7 days), and 14 trials included patients with atrial flutter. The remaining included a mix of paroxysmal, persistent AF and atrial flutter.
Main results
For patients with paroxysmal AF, electrical cardioversion with biphasic incremental energy, fast-acting drugs like intravenous vernakalant, flecainide, ibutilide and antazoline, and slower-acting and/or oral drugs such as quinidine, propafenone, amiodarone and sotalol are effective at restoring sinus rhythm.
For patients with persistent AF, electrical cardioversion with biphasic energy seems to be the most effective option; bepridil, quinidine and amiodarone tablets may also be effective in selected cases.
For patients with atrial flutter, electrical cardioversion followed by dofetilide are the most effective options.
The risk of death and stroke is very low for patients having cardioversion procedures.
Malignant arrhythmias (torsade de pointes, sustained ventricular tachycardia or ventricular fibrillation, all of which are associated with high 1-year mortality rate) were observed for dofetilide, ibutilide, sotalol, quinidine and vernakalant, justifying the need for special care and closer monitoring when using these drugs. Duration of hospitalisation data was available in three studies but, as there were variable timings in these studies, we could not combine them to assess their joint effectiveness. These studies suggest that the duration of hospitalisation may be lower with electrical cardioversion.
Heart failure was observed in some patients treated with propafenone, flecainide, sotalol, amiodarone, vernakalant, and placebo, and was not observed in patients receiving electrical cardioversion, suggesting that the latter approach should be the preferred one if concerns exist regarding the occurrence of this outcome.
Phlebitis (i.e. inflammation of the vein caused by using injectable drugs) occurred frequently in patients treated with amiodarone, and dysgeusia (i.e. impairment of the sense of taste) and sneezing occurred frequently in patients receiving vernakalant.
What are the limitations of the observed results?
We are sure or moderately sure of the results for the efficacy of treatments available for persistent AF and atrial flutter. We are less sure about the results for some of the treatment options for paroxysmal AF.
Not enough data are available regarding quality of life, and data were limited regarding duration of hospital stay. The risk of stroke or dying was very low.
How up to date are the studies and information on this review?
The included studies and information are current to February 2023.
Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter.
In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.
Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion).
To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias.
We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023.
We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes.
We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption.
We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%.
Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains.
For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79).
For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low.
For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%).
The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low.
Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled.