Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Some Cochrane Reviews include network meta-analyses to bring together a range of comparisons to help identify the relative effects of different interventions and to rank them based on effectiveness. In June 2024, we published one of these, examining cardioversion for atrial arrhythmias. In this podcast, one of the authors Rui Providencia interviews the first author, Kishore Kukendra‐Rajah both from Barts Health NHS Trust in London in the UK.

Rui: Hello Kishore, can you give us a brief description of cardioversion for atrial arrhythmias?

Kishore: Hello Rui. Atrial arrhythmias are abnormal heart rhythms originating from the top chambers of the heart, these are mostly atrial fibrillation. Management includes rate control options (to slow down the heart rate), and rhythm control options (to convert the patient to sinus rhythm and maintain it). Cardioversion is in the second category and can be achieved using drugs or by delivering an electrical charge across the heart. Receiving an electrical shock might sound frightening but patients are either sedated or anaesthetised and are closely monitored. 

Rui: Thanks for setting the scene. Moving on to your Cochrane review, why is it important to have a review on the effects of the different pharmacological and electrical methods?

Kishore: There is growing evidence that cardioversion has additional prognostic benefit (on top of good symptom outcomes) and therefore may become more widely used. However, at present, the choice of therapy is determined by local guidelines, physician preference and the availability of anaesthetic support for electrical cardioversion. 
There is no clear preference between pharmacological and electrical methods in international guidelines, except in the case of haemodynamic instability, where electrical is preferred. 
Therefore, we wanted to do this review of the randomised trials to provide evidence that might support recommendations in future guidelines. And, by performing a network meta-analysis, we hope to help clinicians select the best strategy across a broad range of options. 

Rui: And did you find the evidence what you needed? 

Kishore: Yes and no. Our systematic search provided us with 112 randomised trials, but only 72 were suitable for meta-analysis. Furthermore, we had to split our analysis into subtypes of atrial arrhythmia as they have different responses to cardioversion.
All in all, for our quantitative synthesis, we identified 34 trials with nearly 4500 patients reporting efficacy outcomes for conversion to sinus rhythm in paroxysmal AF, 8 trials with approximately 1100 patients for persistent AF patients receiving electrical cardioversion, 12 with just over 1600 patients for persistent AF patients receiving pharmacological cardioversion and 10 with 422 patients for atrial flutter patients receiving pharmacological cardioversion.

Rui: What do these studies tell us?

Kishore: For paroxysmal AF, in a combined network of electrical and pharmacological approaches when compared to placebo, all interventions were better for conversion to sinus rhythm by the end of inpatient study follow up. An electrical protocol with a biphasic truncated exponential waveform and increasing shock energies was ranked the highest followed by quinidine with a moderate degree of certainty. 
With respect to electrical cardioversion for persistent AF we used a protocol with BTE waveform, incremental energies and an anteroposterior (or AP) electrode position with adhesive electrodes as a comparator. We can say with a high degree of certainty that the highest ranked strategy was a protocol almost identical to the comparator but with maximum shock energies. This is followed by another almost identical protocol but with active compression on the pads. In general, patches tended to be ranked higher than paddles for electrode type and AP over anterolateral for electrode position.
For pharmacological cardioversion of persistent AF we used amiodarone as a comparator. We have a moderate degree of certainty that bepridil followed by quinidine are the most efficacious. 
Finally, for pharmacological conversion of atrial flutter patients, among treatments for which we have moderate degree of certainty on efficacy, ibutilide ranked highest followed by propafenone.

Rui: And what about safety outcomes? Was there much difference between cardioversion strategies with respect to stroke or mortality?

Kishore: Most of the studies were not powered appropriately for safety outcomes so overall events found were low, and many studies did not follow patients up for long enough to assess these outcomes. 
For example, from 6 studies comprising just over 1000 patients comparing pharmacological strategies for AF or Flutter, we had a low degree of certainty for any differences between drugs for 30 day all-cause or cardiovascular mortality. Not enough data was available for a meta-analysis of stroke outcomes but overall rates were very low with 0% for electrical cardioversion, less than 0.1% for pharmacological cardioversion and 0% for placebo. 

Rui: To sum up, what are your take home messages for clinicians considering cardioversion for their atrial arrhythmia patients?

Kishore: When considering cardioversion for paroxysmal AF patients, we can be confident that a BTE electrical cardioversion approach with incremental energy is an effective strategy, but several drugs are also effective.
For persistent AF we could not present a combined network comparison between electrical and pharmacological cardioversion. 
However, for pharmacological cardioversion of persistent AF, bepridil and quinidine are probably effective options compared with amiodarone.  
When considering electrical cardioversion for persistent AF patients, a protocol using the BTE waveform, with active compression on the pads or using maximum shock energy likely to be more effective than an incremental shock strategy without compression.
Finally, if attempting pharmacological cardioversion for atrial flutter patients, ibutilide, propafenone, dofetilide and sotalol are probably effective. There were some electrical cardioversion approaches which demonstrated high efficacy rates which we could not perform a meta-analysis on.
For more detail on those and the other comparison please take a look at the summary of findings, figures and text of the review.  

Rui: Thanks Kishore. If people want to look at that detail, where can they find the full review?

Kishore: Thanks Rui. It’s available online at cochranelibrary.com with a simple search for ‘network meta-analysis of cardioversion for atrial fibrillation’.