OBJECTIVE: To conduct a randomised, open label comparison of the effectiveness and safety of intravenous vernakalant and intravenous procainamide for the management of acute atrial fibrillation in the emergency department.
DESIGN: Randomised clinical trial (RAFF4 trial).
SETTING: 12 tertiary care emergency departments in Canada.
PARTICIPANTS: Patients with acute atrial fibrillation for whom acute rhythm control was a safe option.
INTERVENTIONS: Patients were randomised (1:1) to an intravenous infusion of vernakalant or procainamide; when rapid conversion did not occur, patients were offered electrical cardioversion.
MAIN OUTCOMES AND MEASURES: The primary outcome was conversion to sinus rhythm within 30 minutes of drug infusion completion. Secondary outcomes included time to conversion to sinus rhythm and whether the patient required electrical cardioversion.
RESULTS: Of the 350 enrolled eligible patients, baseline characteristics were similar in the procainamide (n=172) and vernakalant (n=178) groups. For the primary outcome of conversion success, vernakalant was more effective (62.4% v 48.3%; adjusted absolute difference 15.0%, 95% confidence interval 4.6% to 25.0%, P=0.005; adjusted odds ratio 1.87, 95% confidence interval 1.2 to 2.9, P=0.006). With vernakalant, time to conversion was faster (21.8 v 44.7 minutes; mean difference -22.9, 95% confidence interval -29.9 to -16.0, P<0.001), and fewer patients underwent attempted electrical cardioversion (33.7% v 44.2%; odds ratio 0.62, 95% confidence interval 0.39 to 0.96, P=0.033). Adverse events were similar in both groups, were generally mild and brief, and most patients were discharged home. Subgroup analysis strongly favoured vernakalant for conversion in patients younger than 70 years (73.3% v 47.2%; adjusted odds ratio 3.1, 95% confidence interval 1.7 to 5.5, P=0.001, interaction P=0.005).
CONCLUSIONS: In this head-to-head comparison, vernakalant was superior to procainamide for patients with higher conversion rates and faster times to conversion. Therefore, vernakalant is a safe and highly effective intravenous alternative for the rapid cardioversion and discharge home of patients with acute atrial fibrillation.
TRIAL REGISTRATION: ClinicalTrials.gov NCT04485195.
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Cardiology |  |
From a cardiology perspective, this is a highly relevant and interesting study that provides valuable comparative data on two pharmacologic cardioversion strategies. However, its direct applicability for someone practicing in the in the United States is limited, as procainamide is not commonly used for rapid AF management and vernakalant is not FDA-approved. From a hospitalist practice standpoint, the findings remain very meaningful given the high frequency of acute AF encounters and the ongoing need for effective and efficient cardioversion options in daily clinical care.
This large multi-centre study shows impressive benefits of vernakalant over procainamide for the ED conversion of atrial fibrillation. When will it be available to me?
This is a randomized, open-label trial (so non-blinded) of intravenous vernakalant vs procainamide for acute atrial fibrillation (AF) in 12 Canadian emergency departments, where it is normally routine for physicians to attempt cardioversion to sinus rhythm, either with drugs or electrically. In intention-to-treat analysis for the primary outcome of conversion success, vernakalant was more effective than procainamide (number needed to treat [NNT]: 7, 95% confidence interval [CI]: 4,22), with a faster time to cardioversion - faster by 23 minutes (95% CI: 16,30) and fewer patients undergoing attempted electrical cardioversion (NNT: 10, 95% CI: 5, 318). Rates of adverse events were less in the vernakalant group (difference not statistically significant, p =0.11), were mild and brief, and 97% of all patients were discharged home. Using vernakalant could prevent the need for procedural sedation for electrical cardioversion in two-thirds of AF patients.