Efficacy and safety of antazoline vs propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm: a randomized, double-blind study (AnProAF).

INTRODUCTION: Antazoline is a frequently used antiarrhythmic drug (AAD); however, to date, no randomized controlled trial has evaluated its efficacy and safety for cardioversion of recent­onset atrial fibrillation (AF) in comparison with other approved AADs. OBJECTIVES: This study aimed to compare clinical efficacy and safety of antazoline and propafenone for a rapid conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure. PATIENTS AND METHODS: This was a single­center, randomized, double­blind study. It included patients with AF (lasting <48 hours) who were in a stable cardiopulmonary condition and eligible for cardioversion. The individuals who fulfilled the inclusion criteria were randomly assigned to receive either antazoline (up to 300 mg) or propafenone (up to 140 mg) intravenously. The primary end point was conversion of AF to sinus rhythm confirmed on electrocardiography. RESULTS: Overall, 94 participants (46 [48.9%] in the antazoline group and 48 [51.1%] in the propafenone group) were included. The mean (SD) age was 67.5 (14) years, and 40 participants (42.5%) were men. Successful AF conversion was observed in 29 patients (63%) from the antazoline group and 25 individuals (52.1%) from the propafenone group (P = 0.39). The median time to conversion was 10 minutes in the antazoline group and 30 minutes in the propafenone group (P = 0.03). Severe adverse events were observed in 5 patients (10.8%) treated with antazoline and 5 individuals (10.4%) who received propafenone. CONCLUSIONS: Intravenous antazoline demonstrated efficacy and safety comparable to those of intravenous propafenone for acute conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure.

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.

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.

Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion.

Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration (FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC50 of 4.321 µmol/L and 2.910 µmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells, with an EC50 of 2.349 µmol/L. These findings provide new ideas for screening and research related to HBV agents.

Pharmacological Cardioversion With Antazoline in Atrial Fibrillation: The Results of the CANT Study.

Background Antazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in comparison to other medications is insufficient. The study aimed to evaluate the success rate and safety of pharmacological cardioversion of atrial fibrillation with intravenous antazoline ( CANT [Cardioversion With Antazoline Mesylate] study) in the setting of the emergency department. Methods and Results After reviewing 1984 medical records, 450 eligible patients (22.7%) with short-duration atrial fibrillation subject to pharmacological cardioversion were enrolled in a retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of the attending physician. The primary end point was successful cardioversion in the emergency department. The safety end point comprised bradycardia <45 bpm, hypotension, syncope, or death. The study population (mean age, 65.5±11.9 years; 52.9% females) was characterized by a median atrial fibrillation episode duration of 10 hours. Antazoline, alone or in combination, was administered in 24.2% (n=109) and 40% (n=180), respectively; amiodarone was administered in 46.7% and propafenone in 9.3%, while ≥2 antiarrhythmic drugs were administered in 19.8% of patients. Antazoline had the highest success rate of pharmacological cardioversion among all drugs (85.3%), which was comparable with propafenone (78.6%; relative risk, 1.09, 95% confidence interval, 0.91-1.30; P=0.317) and higher than amiodarone treatment (66.7%; relative risk, 1.28, 95% confidence interval, 1.13-1.45; P<0.001; number needed to treat, 5.4). The rate of cardioversion with antazoline alone was higher than combined amiodarone and/or propafenone (68.1%; relative risk, 1.25; 95% confidence interval, 1.12-1.40, P=0.0001). No safety end points were reported in the antazoline group, while 5 incidents occurred in the non-antazoline cohort ( P=0.075). Conclusions Antazoline represents an efficacious and safe method of pharmacological cardioversion in a real-life setting.

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.

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.

Antazoline for termination of atrial fibrillation during the procedure of pulmonary veins isolation.

PURPOSE: Pulmonary vein isolation is a well established method of definite treatment of atrial fibrillation (AF). Periprocedural onset of AF usually terminates spontaneously within minutes, but not in all cases. Antazoline is an antihistaminic agent with antiarrhythmic properties. The aim of our retrospective study was to evaluate the efficacy of antazoline in termination of AF in patients undergoing pulmonary vein isolation. MATERIALS AND METHODS: Consecutive 141 patients who received antazoline to terminate AF during pulmonary vein isolation were analyzed. The antazoline was administered at the rate of 30-50mg/min (max. 500mg) after the circumferential ablation in the ostia of pulmonary veins and before confirmation of isolation. Success was defined as restoration of sinus rhythm within 20min after antazoline infusion. RESULTS: The efficacy of antazoline was 83.6% in paroxysmal and 31.1% in persistent AF patients. Clinical variables that were independently predictive of antazoline ineffectiveness were female (odds ratio [OR]: 4.35; 95% confidence interval [CI]: 1.26-14.3; p=0.018) and AF at the beginning of procedure (OR 28.4; 95% CI 3.89-208.0; p=0.001). Due to antazoline related side effects infusion was discontinued in 7 patients (5%). CONCLUSIONS: Antazoline seems to be safe agent in termination of AF in patients undergoing pulmonary vein isolation. We also observed satisfying efficacy, which needs to be proved in a randomized clinical trial.

Neuroprotective activity of antazoline against neuronal damage induced by limbic status epilepticus.

Imidazoline drugs exert neuroprotective effects in cerebral ischaemia models. They also have effects against mouse cerebellar and striatal neuronal death induced by N-methyl-D-aspartate (NMDA) through the blockade of NMDA currents. Here, we investigated the effects of antazoline on NMDA toxicity and current in rat hippocampal neuronal cultures, and on an in vivo model of status epilepticus. In hippocampal cultures, antazoline (30 microM) decreased NMDA-mediated neurotoxicity and also blocked the NMDA current with voltage-dependent and fast-reversible action (inhibition by 85+/-3% at -60 mV). Status epilepticus was induced by injecting pilocarpine (200 nmol) directly into the right pyriform cortex of male adult rats. The rats then received immediately three consecutive i.p. injections at 30-min intervals of either PBS (control group) or antazoline at 10 mg/kg (low-dose group) or at 45 mg/kg (high-dose group). During the 6-h recording, status epilepticus lasted more than 200 min in all groups. In the high-dose group only, seizures completely ceased 1 h after the third injection of antazoline, then started again 1 h later. Rats were killed 1 week later, and Cresyl Violet-stained sections of their brain were analysed for damage quantification. On the ipsilateral side to the pilocarpine injection, pyriform cortex and hippocampal CA1 and CA3 areas were significantly protected in both antazoline-treated groups, whilst prepyriform and entorhinal cortices were only in the high-dose group. On the contralateral side to the pilocarpine injection, only the hippocampal CA3 area was significantly protected in the low-dose group, but all investigated structures were in the high-dose group. In conclusion, antazoline is a potent neuroprotective drug in different models of neuronal primary culture, as previously shown in striatal and cerebellar granule neurons [Neuropharmacology 39 (2000) 2244], and here in hippocampal neurons. Antazoline is also neuroprotective in vivo in the intra-pyriform pilocarpine-induced status epilepticus model.

Effects of Vasocon-A in the allergen challenge model of acute allergic conjunctivitis.

The ophthalmic combination product of 0.05% naphazoline hydrochloride and 0.5% antazoline phosphate (Vasocon-A) was evaluated as an antiallergic agent in 100 subjects with a known allergic history to cat dander, ragweed, or bluegrass pollen. Three independent study sites were used. The allergen challenge model of acute allergic conjunctivitis was selected to assess the agent as it provided a standardized and precise way to measure drug effectiveness for this indication. In a double-masked randomized fashion, the subjects were assigned to one of three groups that received one drop of Vasocon-A in one eye and one drop of either 0.05% naphazoline (group 1), 0.5% antazoline (group 2), or placebo (group 3) in the contralateral eye. After 10 minutes, the dose of allergen shown to elicit a 2+ redness and itching reaction was instilled bilaterally. Signs and symptoms of allergic conjunctivitis were evaluated after 3, 5, and 10 minutes. Subjects were then rechallenged 2 hours after drug administration to assess the duration of action of the agents. Vasocon-A was found to significantly inhibit all five major signs and symptoms of allergic conjunctivitis: itching, redness, chemosis, lid swelling, and tearing, for more than 85% of the comparisons when compared over time with placebo, naphazoline alone, or antazoline alone. The results of this study indicate that the combination of naphazoline and antazoline was more effective in inhibiting redness than naphazoline and more effective in inhibiting itching than antazoline. These findings support the use of such a combination for the treatment of allergic conjunctivitis.

Effects of topically applied occular decongestant and antihistamine.

In two independent studies including 25 subjects each, naphazoline caused significant whitening (but did not prevent itching) in the histamine-induced red, itchy eye. Antazoline inhibited itching (but not redness) to a significant degree in the same model. The combination of naphazoline and antazoline produced significant whitening and inhibition of itching in all eyes challenged by histamine. The combination of the two drugs was more effective than either component alone in preventing redness. The antihistamine and combination of antihistamine/vasoconstrictor were equally effective in arresting itching.

Influence of antazoline and ketotifen on the anticonvulsant activity of conventional antiepileptics against maximal electroshock in mice.

Experimental studies have indicated that the central histaminergic system plays an important role in the inhibition of seizures through the stimulation of histamine H1 receptors. H1 receptor antagonists, including classical antiallergic drugs, occasionally may induce convulsions in healthy children and patients with epilepsy. The purpose of this study was to investigate the effects of antazoline and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of antiepileptic drugs against maximal electroshock (MES)-induced convulsions in mice. The following antiepileptic drugs were used: valproate, carbamazepine, diphenylhydantoin and phenobarbital. In addition, the effects of antiepileptic drugs alone or in combination with antazoline or ketotifen were studied on long-term memory (tested in the passive avoidance task) and motor performance (evaluated in the chimney test), acutely and after 7-day treatment with these H1 receptor antagonists. The influence of antazoline and ketotifen on the free plasma and brain levels of the antiepileptics was also evaluated. Antazoline (at 0.5 mg/kg), given acutely and after 7-day treatment, significantly diminished the electroconvulsive threshold. Similarly, ketotifen, after acute and chronic doses of 8 mg/kg markedly reduced the threshold for electroconvulsions. In both cases, antazoline and ketotifen were without effect upon this parameter at lower doses. Antazoline (0.25 mg/kg) significantly raised the ED50 value of carbamazepine against MES (both, acutely and after 7-day treatment). Furthermore antazoline (0.25 mg/kg) also reduced the anticonvulsant activity of diphenylhydantoin, but only after repeated administration, without modifying the brain and free plasma level of this drug. Moreover, valproate and phenobarbital did not change their protective activity when combined with antazoline. Ketotifen (4 mg/kg) possessed a biphasic action, acutely it enhanced the anticonvulsant action of carbamazepine and phenobarbital while, following 7-day treatment, reduced the antiseizure activity of carbamazepine. Ketotifen did not affect the free plasma or brain levels of antiepileptics tested. Only acute antazoline (0.25 mg/kg) applied with valproate impaired the performance of mice evaluated in the chimney test. Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs impaired motor coordination in mice treated with valproate, phenobarbital or diphenylhydantoin. Acute and chronic antazoline (0.25 mg/kg) alone or in combination with antiepileptic drugs did not disturb long-term memory, tested in the passive avoidance task. Similarly, ketotifen (4 mg/kg) did not impair long-term memory, acutely and after 7-day treatment. However, valproate alone or in combination with chronic ketotifen (4 mg/kg) worsened long-term memory. The results of this study indicate that H1 receptor antagonists, crossing the blood brain barrier, should be used with caution in epileptic patients. This is because antazoline reduced the protective potential of diphenylhydantoin and carbamazepine. Also, ketotifen reduced the protection offered by carbamazepine and elevated the adverse activity of diphenylhydantoin, phenobarbital and valproate.

Clinical trial with 2% sodium cromoglycate (Opticrom) in vernal keratoconjunctivitis.

An open assessment study was carried out during the summer of 1972 in which 2% sodium cromoglycate eyedrops were evaluated in the treatment of patients with vernal keratoconjunctivitis. A highly significant number of patients found the eyedrops effective, while a marked improvement was recorded in mild and moderate cases; in severe cases or in acute exacerbations additional steroid therapy was recommended. Sodium cromoglycate eyedrops were found to be as effective as Decadron and superior to Antistin-Privine. Furthermore SCG eyedrops could replace or reduce local steroid therapy in vernal keratoconjuntivitis and so avert the possible rise in ocular tension caused by steroids.

[A case of allergic reaction to the sting by the bee]. / Przypadek reakcji alergicznej na ukaszenie przez ose.

The authors described a case of an insect sting allergy, of a 19 year old patient. They discuss the treatment and prevention in such cases and situations.

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.