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.

Rapid pharmacological cardioversion of recent-onset atrial fibrillation using antazoline in elderly patients.

INTRODUCTION: There is insufficient evidence on the efficacy and safety of pharmacological cardioversion of recent­onset atrial fibrillation (AF) in elderly patients. Antazoline has been shown to be effective and safe in various patient populations. OBJECTIVES: We aimed to compare the clinical efficacy and safety of intravenous antazoline for pharmacological cardioversion of recent­onset AF between patients aged 75 years or older and those younger than 75 years. PATIENTS AND METHODS: This retrospective analysis was conducted using data derived from emergency room medical records of patients referred for pharmacological cardioversion due to symptomatic AF lasting less than 48 hours. The threshold for old age was set at 75 years. Conversion to sinus rhythm was considered the primary efficacy outcome. The primary safety outcome was defined as any adverse event requiring hospitalization. RESULTS: The study included 334 participants, of whom 110 patients were aged 75 years or older (study group) and 224 patients were younger than 75 years (controls). Successful cardioversion was achieved using lower mean (SD) antazoline doses in the study group than in controls: 151 (59) mg vs 168 (58) mg (P = 0.039). Study and control groups showed a similar efficacy and safety of antazoline (78.2% and 68.3%, respectively; odds ratio [OR], 1.66; 95% CI, 0.98-1.31; P = 0.06) as well as hospitalization rates (0.9% and 4.0%, respectively; OR, 0.22; 95% CI, 0.03-1.75; P = 0.17). CONCLUSIONS: Intravenous antazoline seems to be effective and safe for pharmacological cardioversion of recent­onset AF in elderly patients in the emergency setting.

Exposure to antazoline-naphazoline eye drops during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study.

PURPOSE: To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans. METHODS: All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring. RESULTS: We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05). CONCLUSION: Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.

Clinical effectiveness and safety of antazoline-based therapy in patients with stable coronary artery disease undergoing pharmacological cardioversion of short-duration atrial fibrillation in the emergency department.

INTRODUCTION: Options for a pharmacological cardioversion (CV) of short-duration atrial fibrillation (AF) in patients with a stable coronary artery disease (CAD) are limited to amiodarone or vernakalant. Antazoline has been reported to achieve high rates of AF conversion to sinus rhythm, but data on its effectiveness and, more importantly, safety in stable CAD patients, have been sparse. AIMS: To assess the effectiveness and safety of antazoline-based therapy in patients with a stable CAD undergoing pharmacological CV of short-duration AF in the emergency department (ED). RESULTS: A retrospective case-control study. We conducted an analysis of medical records of patients with a stable CAD undergoing CV of short duration (≤48 hours) AF in the ED using intravenous antazoline. The main endpoints of the study were successful cardioversion of AF and hospitalization due to the adverse effects (AE) of the treatment. Between 2008 and 2012, out of 548 CVs, antazoline was administered 334 times: 138 in CAD and 196 in the control group. Patients in the CAD group were older and had more comorbidities than controls; 65 patients had had a history of myocardial infarction (MI). In CAD group, the effectiveness was higher (82.6% vs 63.8%, RB: 1.30 [95% CI: 1.14-1.48], P = 0.0002) and the hospitalization rate due to AE was similar (1.4% vs 4.1%, RR: 0.36 [95% CI: 0.08-1.65], P = 0.2054) to the control group. Among patients with CAD, a history of MI did not influence the effectiveness or safety of the CV (P = 0.2252 and P = 1.0000, respectively). CONCLUSIONS: In selected patients with a stable CAD, even with a history of MI, antazoline-based CV of short-duration AF may be an effective and safe therapeutic option.

Efficacy and safety of antazoline in the rapid cardioversion of paroxysmal atrial fibrillation (the AnPAF Study).

AIMS: The aim of the study was to assess the clinical efficacy of antazoline, a first-generation anti-histaminic agent, in the rapid conversion of paroxysmal non-valvular atrial fibrillation (AF) to sinus rhythm in patients without heart failure. METHODS AND RESULTS: This study was a single center, randomized, double blind, placebo-controlled, superiority clinical trial. We enrolled patients with an AF episode lasting less than 43 h, in stable cardiopulmonary condition. Subjects who fulfilled the selection criteria were randomly assigned to receive intravenously either a placebo or up to 250 mg of antazoline. The primary end point was the conversion of AF to sinus rhythm confirmed in electrocardiogram (ECG). We enrolled 74 patients: 36 (48.6%) in the antazoline group and 38 (51.4%) in the control group. The mean age was 68 ± 12 years (range 31-90 years), 39 (53.3%) patients were male. The successful conversion of AF to sinus rhythm during the observation period was achieved in 26 (72.2%) patients treated with antazoline and 4 (10.5%) in the control group: RR 6.86 (95% CI: 2.66-17.72, P < 0.0001). Median time to conversion was 16.0 min in antazoline and 72.5 min in the control group (P = 0.0246). There were no cases of atrial tachycardia/flutter in the antazoline group. CONCLUSION: Intravenous antazoline was effective and safe in the rapid conversion of non-valvular paroxysmal atrial fibrillation to sinus rhythm in patients without heart failure. Clinical Trial Registration number: NCT01527279.

Comparative effectiveness and safety of antazoline­based and propafenone­based strategies for pharmacological cardioversion of short­duration atrial fibrillation in the emergency department.

INTRODUCTION    Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short­duration atrial fibrillation (AF). However, there are no data on the comparison of antazoline and antiarrhythmic drugs listed in clinical guidelines. OBJECTIVES    The aim of the study was to assess the comparative effectiveness and safety of antazoline­based and propafenone­based strategies in pharmacological cardioversion of short­duration AF performed in our emergency department. PATIENTS AND METHODS    We conducted a retrospective case­control study based on the analysis of medical records of patients undergoing pharmacological cardioversion of short­duration AF with intravenous antazoline or propafenone at our department in the years 2008-2012. The primary endpoint was the successful cardioversion of AF. The primary safety endpoint was hospitalization due to the adverse effects of the treatment. RESULTS    We analyzed 432 cases of cardioversion. The mean age of patients was 68.9 ±9.8 years; 65% of the patients were male; 90% of the patients had a history of AF. Antazoline was administered 334 times and propafenone-98 times. The mean dose of antazoline was 172 ±65 mg, while all patients in the propafenone group received the drug at a fixed dose of 70 mg (1 vial). Cardioversion with antazoline was successful in 239 cases (71.6%) and with propafenone-in 54 patients (55.1%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.07-1.57). The rate of hospitalization due to the adverse effects of the treatment were low and similar between the study groups: 10 (3.0%) for antazoline and 4 (4.1%) for propafenone (RR, 0.73; 95% CI, 0.23-2.27). CONCLUSIONS    The antazoline­based strategy was more effective and safer in comparison with propafenone­based strategy in the pharmacological cardioversion of short­duration AF in our emergency department.

Clinical efficacy of antazoline in rapid cardioversion of paroxysmal atrial fibrillation--a protocol of a single center, randomized, double-blind, placebo-controlled study (the AnPAF Study).

BACKGROUND: Rapid conversion of atrial fibrillation (AF) to sinus rhythm may be achieved by the administration of class IA, IC and III antiarrhythmic drugs or vernakalant hydrochloride. However, that treatment may be related to potential pro-arrhythmia, lack of efficacy or the exceptionally high cost of a compound used. Antazoline is a first generation antihistaminic agent with chinidin-like properties. When administered intravenously, antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia, especially on AF, facilitating rapid conversion to sinus rhythm. Despite a relative lack of published data antazoline has been marketed in Poland and widely used in cardiology wards and emergency rooms for many years due to its efficacy, safety and rapid onset of action within minutes of administration. METHODS/DESIGN: A randomized, double blind, placebo-controlled, superiority clinical trial was designed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm. Eligible patients will present AF lasting less than 43 hours, will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease. Long-term antiarrhythmic therapy is not considered an exclusion criterion. Subjects who fulfill selection criteria will be randomly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v. bolus. Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram (ECG) during the observation period. Secondary end points will be comprised of time to conversion and return of AF during the observation period. Special consideration will be given to the observation of any adverse events. A sample size of 80 patients was calculated based on the following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of antazoline 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to the presumed lack of statistical power, the secondary end points and safety endpoints will be considered exploratory. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov, NCT01527279.

[Antazoline/tetryzoline eyedrops in comparison with levocabastine eyedrops in acute allergic conjunctivitis]. / Antazolin/Tetryzolinhaltige Augentropfen im Vergleich zu Levocabastinhaltigen Augentropfen bei akuter allergischer Konjunktivitis.

BACKGROUND: Allergic conjunctivitis is one of the most frequent allergic diseases of the anterior eye segment. METHODS: This multicentre, clinical trial was an investigation to compare the antiallergic efficacy, local tolerance and safety of Antazolin/Tetryzolin eye drops and Levocabastine eye drops. 69 patients were treated over a 2 weeks course of therapy. The subjective and objective ocular symptoms were documented over the treatment period. RESULTS: Both eye drops reduced subjective and objective ocular symptoms effective. The difference between the treatments (p = 0.0395) was the faster onset of action of Antazolin/Tetryzolin 30 minutes after administration of the first drop of trial medication. CONCLUSION: A fast and effective onset of action is of high clinical relevance. Therefore the benefits of using Antazolin/Tetryzolin eye drops was clearly outweigh.

[Nitrosamine formation via non-prescription drugs?]. / Nitrosamindannende håndkøbspraeparater?

Both carcinogenic and non-carcinogenic nitrosamines can be formed under physiological conditions in the human body as a reaction between nitrite and a secondary or tertiary amine. A major part of the population is exposed daily through drinking water to high levels of nitrate, which can be reduced to nitrite. Moreover, nitrate and nitrite are both present in vegetables and nitrite is used in food preservation. Dietary exposure to amines is normally well below 100 mg per day, whereas paracetamol and antazoline, both secondary amines, are used therapeutically at much higher doses. Knowledge about the possible interactions between these widely used drugs and the background exposure to nitrite is presently not available. Therefore, an evaluation of the carcinogenic hazard related to this combination is needed.

Otrivine-antistin-pupil, corneal and conjunctival responses to topical administration.

The ocular effects of Otrivine-Antistin eyedrops have been measured in a placebo controlled single-blind study in sixteen healthy volunteers. The drops produced mild sympathomimetic responses in the eye but had no effect on corneal sensitivity or on intraocular pressure. The evidence indicates that use of Otrivine-Antistin imposes no risk to the subject.

Immune thrombocytopenia due to antazoline (Antistina).

Antazoline (Antistina)-induced thrombocytopenic purpura occurring on three occasions in a 21-year-old woman is reported. After withdrawal of the drug ther recovered promptly. In vitro investigation demonstrated the presence of an antibody in serum, which in association with antazoline caused complement fixation when added to test platelets. Also platelet agglutinins could be detected in the patient's serum when antazoline was added. The reactions were drug specific and they could still be demonstrated 9 months after the last exposure to the drug.

Antazoline-induced immune hemolytic anemia, hemoglobinuria, and acute renal failure.

A case of repeated antazoline-induced immune hemolytic anemia, thrombocytopenia, hemoglobinuria, and acute renal failure is reported. The first episode of renal failure occurred after an i.v. pyelography causing an anaphylactic shock, and the two later episodes were preceded by allergic reaction to drugs. Antazoline was given among other remedies, but this drug was the only one used for treatment on every occasion. The clinical picture and the immunological tests, including an antazoline-dependent Coombs' test, indicate that the blood disorders might have been caused by a type 2 allergic reaction and renal lesion by a type 3 reaction, at least on the second and third occasions.

Antazoline therapy of recurrent refractory supraventricular arrhythmias--a preliminary report.

Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled ventricular response could not be achieved with quinidine, procainamide, digitalis or propranolol. Sinus rhythm was established by either intravenous administration of antazoline or direct-current countershock, and has been maintained in all for 4 to 16 months by oral administration of antazoline. Side effects were minor. Antazoline is a sufficiently promising antiarrhythmic agent to warrant large-scale controlled studies.