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Three Part Question

For [patients presenting to the ED in atrial fibrillation] is [ibutilide more effective than other antiarrhythmic drugs] in [successful cardioversion and safety]?

Clinical Scenario

A 41-year-old male with a past medical history of symptomatic paroxysmal atrial fibrillation (on metoprolol), hypertension, diabetes, morbid obesity, and chronic alcoholism was BIBA to the ED for palpitations and light-headedness that started one hour prior. Electrocardiogram and labs showed atrial fibrillation without RVR and ST changes, and a normal CK, troponin level, and chemistry panel. The patient claimed to be adherant with all medications and was on the maximum dose of metoprolol. He last ate a large meal one hour ago. The patient claims that flecainide, propafenone, amiodarone, and procainamide have been ineffective in the past for cardioversion and that he does not want to try any of them again. In an attempt to cardiovert this patient back to normal sinus rhthym, you wonder if ibutilide should be used.

Search Strategy

MEDLINE 1996-6/2017 using the OVID interface: [Atrial Fibrillation] AND [Ibutilide] AND [Cardioversion OR Conversion] LIMIT to Human AND English Language AND Last 15 Years

Search Outcome

A total of 82 articles were identified, of which 4 were relevant to the clinical question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Kriz R, Freynhofer MK, Weiss TW, Egger F, Gruber SC, Eisenburger P, Wojta J, Huber K, Koch J. 2016	236 patients presenting with <48h onset AFib receiving either ibutilide (n=107), vernakalant (n=68), or flecainide (n=59) for cardioversion.	Prospective observational study	Success of cardioversion in ibutilide, vernakalant, or flecainide group.	No statistically significant difference between the groups.	Observational study, not randomized, no blinding, single center, and relatively small sample size.
			Ischemic events, deaths, or other events in ibutilide, vernakalant, or flecainide group.	No statistically significant difference between the groups. One death from embolic stroke 24h after ibutilide.
Hirschl MM, Wollmann C, Globits S. 2011	376 patients presenting with <48h onset AFib given either ibutilide (n=50), amiodarone (n=44), or flecainide (n=44) for cardioversion.	Prospective observational study	Success of cardioversion in ibutilide, amiodarone, or flecainide group.	Flecainide was significantly more effective than ibutilide and amiodarone (95% vs. 76%, and 95% vs. 36%, respectively). Ibutilide was significantly more effective than amiodarone (76% vs. 36%).	Observational study, not randomized, no blinding, single center, relatively small sample size.
			Secondary outcomes of hypotension, polymorphic ventricular tachycardia, bradycardia, and ventricular tachycardia.	No statistically significant difference between the groups. No deaths reported in any groups.
Zhang N, Guo JH, Zhang HCh, Li XB, Zhang P, Xn Y. 2005	82 patients presenting with AFib onset of 2h-90d that were given either ibutilide (n=41) or propafenone (n=41) for cardioversion.	Single blinded randomized controlled trial	Success of cardioversion with ibutilide, or propafenone group.	Ibutilide was significantly more effective than propafenone (70.7% vs. 48.8%).	Single center, single blinding only, small sample size, and included patients with wide range of atrial fibrillation onset.
			Secondary outcomes of hypotension, aberrancy, QTc >500ms, prolonged PQ, bradycardia, ventricular pause, ventricular ectopics, ventricular tachycardia, and polymorphic ventricular tachycardia.	Propafenone had significantly less adverse events overall compared with ibutilide (34% vs. 54%). No deaths in either group.
Reisinger J, Gatterer E, Lang W, Vanicek T, Eisserer G, Bachleitner T, Niemeth C, Aicher F, Grander 2004	207 patients presenting with <48h onset AFib receiving either ibutilide (n=106) or flecainide (n=101) for cardioversion.	Single blinded randomized controlled trial	Success of cardioversion with ibutilide, or flecainide group.	No significant differences between the groups (50.0% vs. 56.4%).	Single center, only single blinded, and relatively small sample size.
			Secondary outcomes of chest pain, dizziness, hypotension, acute congestive heart failure, atrial flutter, bradycardia, bifasicular block, ventricular tachycardia, and polymorphic ventricular tachycardia.	No statistically significant differences between the groups. No deaths in either group.

Comment(s)

While there are no large, multi-center, randomized controlled trials comparing ibutilide’s efficacy and safety in cardioverting patients in atrial fibrillation to other anti-arrhythmic drugs, the small randomized controlled trials and observational studies shown herein seem to suggest that ibutilide is more effective than some antiarrhythmic drugs. Although the fear of prolonged QTc leading to Torsades de Pointes often prohibits Emergency Medicine physicians from using the agent, it seems that this risk is rarely of any clinical significance to the patient based on these studies as there were no major differences in side effects in patient. The only death seen with ibutilide in these studies was from an embolic stroke, which is a known adverse event after any form of cardioversion due to risk of atrial thrombus formation after NSR is established.

Clinical Bottom Line

In comparison with other anti-arrhythmics in safely and successfully cardioverting patients in atrial fibrillation to normal sinus rhythm, ibutilide seems to be at least as effective as some anti-arrhythmics and better than others with similar odds of adverse events, most of which are transient and benign. With adequate surveillance, ibutilide is an effective anti-arrhythmic in patients who cannot tolerate synchronized electrical cardioversion and/or who have previously failed pharmacologic cardioversion with other antiarrhythmic medications.

References

1. Kriz R, Freynhofer MK, Weiss TW, Egger F, Gruber SC, Eisenburger P, Wojta J, Huber K, Koch J. Safety and efficacy of pharmacological cardioversion of recent-onset atrial fibrillation: a single-center experience The American Journal of Emergency Medicine 2016; 34(8):1486-1490
2. Hirschl MM, Wollmann C, Globits S. A 2-year survey of treatment of acute atrial fibrillation in an ED The American Journal of Emergency Medicine 2011; 29(5): 534-540
3. Zhang N, Guo JH, Zhang HCh, Li XB, Zhang P, Xn Y. Comparison of intravenous ibutilide vs. propafenone for rapid termination of recent onset atrial fibrillation International Journal of Clinical Practice 2005; 59(12): 1395-1400
4. Reisinger J, Gatterer E, Lang W, Vanicek T, Eisserer G, Bachleitner T, Niemeth C, Aicher F, Grander Flecainide versus ibutilide for immediate cardioversion of atrial fibrillation of recent onset European Heart Journal 2004; 25(15): 1318-1324