Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.

BACKGROUND: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. METHODS: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. RESULTS: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. CONCLUSION: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

Pharmacological Cardioversion in Patients with Recent-Onset Atrial Fibrillation and Chronic Kidney Disease Subanalysis of the CANT II Study.

Pharmacological cardioversion (PCV) is commonly a primary option for termination of recent-onset atrial fibrillation (AF) in emergency departments (ED). This is a subanalysis of the CANT II study, evaluating the effectiveness and safety of antazoline in patients (n = 777) at three stages of chronic kidney disease (CKD): Group I > 60 mL/min (n = 531), Group II 45−59 mL/min (n = 149), and Group III < 45 mL/min (n = 97). Patients in Group III were older and with a higher prevalence of co-morbidities; however, we did not find statistically significant differences in the overall effectiveness of PCV in comparison with the other groups. In patients receiving amiodarone, the PCV success rate was similar in all the studied groups, but along with a renal function decline, it decreased in patients receiving antazoline (79.1 vs. 35%; p < 0.001), and it increased almost significantly in patients receiving propafenone (69.9 vs. 100%; p = 0.067). In patients in Group I, antazoline restored a sinus rhythm as effectively as propafenone and amiodarone; however, in patients in Group III, both antazoline and amiodarone became less effective in restoring a sinus rhythm than propafenone (p = 0.002 and p = 0.034, respectively). The rate of safety endpoint was the highest in patients in Group III (eGFR < 45 mL/min), and it was significantly higher than in patients in Groups I and II (p = 0.008 and p = 0.036, respectively). We did not observe antazoline-related adverse events in any of the studied groups of patients. This real-world registry analysis revealed a different influence of CKD on the effectiveness of individual drugs, and while propafenone and amiodarone maintained their AF termination efficacy, antazoline became significantly less effective in restoring sinus rhythm.

Efficacy and safety of antazoline for cardioversion of atrial fibrillation: propensity score matching analysis of a multicenter registry (CANT II Study).

INTRODUCTION: Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of antazoline, a first­generation antihistamine, for cardioversion of recent­onset AF in the setting of an emergency department. PATIENTS AND METHODS: This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with new­onset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment. RESULTS: Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P <0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the post­PSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P <0.001), and the risk of adverse events was comparable (P = 0.2). CONCLUSIONS: Antazoline appears to be an efficacious agent for termination of AF in real­world setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.