Efficacy and Safety of Ibutilide for the Cardioversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Review Article

Austin Surg Case Rep. 2021; 6(1): 1041.

Efficacy and Safety of Ibutilide for the Cardioversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Gong CC¹, Tang Y², Huang Y² and Liu X²*

¹Zhejiang University School of Medicine Children’s Hospital, China

²Department of Critical Care Medicine, the Affiliated Hospital of Guizhou Medical University, China

*Corresponding author: Liu X, Department of Critical Care Medicine, the Affiliated Hospital of Guizhou Medical University, China

Received: February 16, 2021; Accepted: March 17, 2021; Published: March 24, 2021


Background: Ibutilide has been approved for cardioversion of Atrial Fibrillation (AF), but its side-effects include a high risk of torsade de pointes, besides, one recent meta-analysis showed ibutilide was inferior to vernakalant for conversion (AF<7 days). Hence, the aim of this study is to evaluate the efficacy and safety of ibutilide for the cardioversion of AF within 90 days.

Methods: The Embase, PubMed, Web of Science, Cochrane Central databases and clinical trials.gov were comprehensively searched for relevant studies from January 1991 to May 2020 using the keywords “ibutilide” and “atrial fibrillation”. Only Randomized Controlled Trials (RCTs) comparing ibutilide with placebo or other Anti-Arrhythmic Drugs (AADs) for the termination of AF (duration of AF ≤90 days) were included. The primary outcome was successful cardioversion in response to ibutilide versus placebo or other AADs within 4h. Related adverse events were defined as secondary outcomes.

Results: A total of 1712 patients in 13 RCTs met the eligibility criteria. Four trials compared ibutilide to placebo; nine trials compared ibutilide to other active drugs. The results revealed that ibutilide had a higher success rate for the termination of recent-onset atrial fibrillation compared to placebo within 4h [Risk Ratio (RR), 4.64; 95% Confidence Interval (CI), 1.30-16.56, P=0.006]; and ibutilide also showed superiority to DL-sotalol, Propafenone, Procainamide for successful termination of recent-onset AF within 4h. As compared to other active drugs, Ibutilide was associated with a lower risk of hypotension (RR 0.23, 95% CI 0.09-0.57, P=0.002); but significantly increased the incidence of Polymorphic ventricular tachycardia (RR 3.78, 95% CI 1.08-13.23, P=0.04).

Conclusion: Intravenous ibutilide could be an accessible choice for the cardioversion of recent-onset AF patients without contraindications, but under strict monitored condition is needed for at least 6 hours.

Keywords: Atrial fibrillation; Cardioversion; Ibutilide; Meta-analysis


AF: Atrial Fibrillation; AADS: Anti-Arrhythmic Drugs; RR: Risk Ratio; CI: Confidence Interval; RCTs: Randomized Controlled Trials


Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia, occurring in 1-2 % of the general population. Patients with AF have an increased risk of death, hospitalizations, and a lower quality of life [1]. Sinus restoration can relieve rhythm-related symptoms and attenuate functional impairment [2-4]. As such, early chemical or electrical conversion is the preferred choice for the treatment of AF, but electro cardioversion requires sedation or anesthesia [5], which limits its use. Pharmacological treatment is therefore more appealing for the conversion of recent-onset AF.

Ibutilide is a class III intravenous anti-arrhythmic agent that blocks the rapid component of the cardiac delayed rectifier potassium current and activates a late inward sodium current [6]. Ibutilide has been approved for the termination of recent-onset atrial fibrillation and atrial flutter [7]. However, given the limited sample size in previous trials [8-10], the superiority of ibutilide over other Anti- Arrhythmic Drugs (AADs) remains undefined. The aim of this review was to investigate the effectiveness and safety of ibutilide for the conversion of recent-onset AF compared with placebo and other AADs.


This meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions [11] and presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PRISMA Guidelines) [12].

Search strategy

Two researchers (Gong C, and Tang Y) independently performed a comprehensive literature search. Trials comparing ibutilide with placebo or other AADs for the termination of recent-onset AF (duration of AF ≤90 days) were retrieved from PubMed, Embase, Web of Science, the Cochrane Library and Clinical Trials.gov until May, 2020. A basic search was carried out using the key words as follows: (“atrial fibrilation” or “atrial arrhythmia”) and (“ibutilide” or “ibutilide fumarate”). No language limitation was applied for the selection of articles.

Eligibility criteria

Trials were selected based on the following inclusion criteria: (1) Adult patients; (2) Ibutilide versus placebo or other AADs for treatment of recent-onset AF (duration of AF =90 days); (3) Randomized controlled trials.

Quality assessment

The methodological quality for the included studies was evaluated separately by two researchers(Gong C and Tang Y) using the Cochrane risk of bias criteria [11] and each quality item was graded as low risk, high risk, or unclear risk. We defined other bias as trials in which baseline characteristics were significant variation between different treatment groups. The included trials were graded as low quality, high quality or moderate quality based on the criteria in the following: (1) trials were evaluated as low quality if either randomization or allocation concealment was assessed as a high risk of bias, without taking the risk of other items into consideration; (2) trials were considered as high quality when both randomization and allocation concealment were assessed as a low risk, along with all other items assessed as low or unclear risk of bias in a trial; (3) trials were considered as moderate quality if they did not meet criteria for high or low quality [13].

Data extraction

The following information from each trial was extracted independently by two researchers (Fang H and Huang Y): first author, year of publication, country of origin, sample size, treatment strategies, the duration of AF, the time point for evaluating conversion efficacy, the length of follow-up and patient population. Disagreements on data extraction and quality assessment between the 2 reviewers were resolved by consensus (Liu X).


The primary outcome was the success conversion rate of AF within 4h, secondary outcomes were as follows: the incidence of Polymorphic ventricular tachycardia and hypotension.

Statistical analysis

Risk Ratio (RR) with 95% Confidence Interval (CI) were calculated for dichotomous data. Analyses were performed using Review Manager 5.3 (Revman: The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). We assessed the heterogeneity among studies using Cochran’s Q-test (P<0.05 for statistical significance) and the I2 index (I2>50% for substantial heterogeneity). The random-effect model was chosen to pool the data.


Selection of studies

Following the database search, a total of 1386 studies were identified. After the removal of duplications, 961 studies were screened according to titles and abstracts. Then, full texts of 26 potentially eligible trials were assessed based on predefined eligibility criteria. A total of 13 eligible trials were finally included in the metaanalysis (Figure1).