[A randomized double-blind trial comparing cibenzoline and disopyramide in the prevention of recurrences of atrial tachyarrhythmia]. / Etude randomisée en double aveugle comparant la cibenzoline et le disopyramide dans la prévention de récidives de tachyarythmies atriales.

The aim of this multicenter, randomised, double-blind trial was to compare the efficacy and tolerance of oral disopyramide (D: 250 mg slow release twice daily) compared with cibenzoline (C: 130 mg twice daily) in the prevention of recurrences of atrial arrhythmias over a 6 month period. Sixty patients (mean age: 62 +/- 14 years; 37 men, 23 women; cardiac disease in 60% of cases) were randomised to two groups: C (N = 31) and D (N = 29). The commonest arrhythmia was atrial fibrillation (83%). The arrhythmia was recent (< 3 months) in 41% of patients and present for more than one year in 38% of patients. Sixteen patients of Group C (52%) and 11 of Group D (38%) had recurrences after an average of 79 +/- 58 days for Group C and 58 +/- 40 days for Group D (p = NS). The probability of absence of recurrence at 6 months was 36 +/- 11% in Group C and 55 +/- 10% in Group D (p = NS). Four patients in Group C (13%) and 13 patients in Group D (45%) had at least one unwanted side-effect (p = 0.009). Treatment was stopped because of side-effects in 2 patients in group C (6%) and 6 patients in Group D (21%). These results show that cibenzoline has a comparable efficacy for the prevention of recurrence of atrial tachyarrhythmia and is significantly better tolerated than disopyramide. This differences is mainly related to the marked anticholinergic effects of disopyramide.

[Comparison between effects of morning and evening administration of effervescent calcium carbasalate (equivalent of 160 mg aspirin) on the gastroduodenal mucosa in healthy volunteers]. / Comparaison de l'effet de la prise matinale et vespérale du carbasalate calcique effervescent (equivalent a 160 mg d'aspirine) sur la muqueuse gastroduodénale chez le volontaire sain.

The aim of this randomised, cross-over trial was to compare the gastroduodenal tolerability and anti-aggregating effect of effervescent calcium carbasalate (ECC equivalent to 160 mg aspirin) given once daily either in the morning or in the evening. Twelve healthy volunteers received calcium carbasalate for 2 periods of 5 days (21 days of wash-out between the 2 periods). The principal criterion was the gastroduodenal tolerability assessed by the total number of lesions at upper gastro-intestinal endoscopy. The same treatment-blinded endoscopist performed all evaluations. Efficacy was evaluated by thromboxane B2 measurement and collagen-induced platelet aggregation tests. No difference was observed between morning and evening administration of ECC on gastroduodenal tolerability and platelet agregation. ECC was very well tolerated as assessed by upper gastrointestinal endoscopy and almost totally inhibited platelet aggregation.

[Comparative study of cibenzoline and flecainide by oral route for preventing recurrence of paroxysmal atrial tachyarrhythmias]. / Etude comparative de la cibenzoline et du flécaïnide administrés par voie orale dans la prévention de récidive des tachyarythmies auriculaires paroxystiques.

Although paroxysmal atrial arrhythmias are the commonest form of arrhythmia, their therapeutic management still remains controversial. Seventy one patients were included in a multicentre, randomized double-blind, double-placebo study, in parallel groups (37 in group C and 34 in group F) to compare the efficacy of cibenzoline (C) and flecainide (F), administered orally, in the prevention of recurrent atrial arrhythmia. The arrhythmia usually consisted of atrial fibrillation (n = 65), while 6 patients presented with paroxysmal atrial flutter. The mean daily dosages were 221 +/- 60 mg (C) and 165 +/- 49 mg (F). The mean age was 63 +/- 12 years in group C and 63 +/- 16 years in group F. In this trial, atrial arrhythmia was idiopathic in almost two-thirds of cases. The duration of follow-up of this study was 6 months, during which recurrences of arrhythmia were evaluated in terms of the symptoms experienced and in terms of ECG and Holter examinations repeated at the 3rd and 6th months. Supplementary ECG and Holter examinations were also performed in the presence of a clinical suspicion of recurrent symptoms. Comparison of the percentages of patients not developing a documented recurrence and who tolerated treatment, by Kaplan-Meler curves, showed a significant difference between cibenzoline (58%) and flecainide (56%). In the not-responders, the mean time to recurrence was 75 +/- 48 days in group C and 75 +/- 62 days in group F(NS). Six patients dropped out of the trial because of adverse events, including 3 cardiac adverse events (2 case of ventricular proarrhythmic activity). Four extracardiac adverse events led to discontinuation of treatment in group C. In conclusion, the efficacy of cibenzoline and flecainlde in the secondary prevention of atrial arrhythmia was found to be comparable, with 58% and 58% of patients in sinus rhythm, respectively, with a follow-up of 6 months.

[Gastroprotective effect of an antacid coating agent in rats. Role of endogenous prostaglandins, capsaicin-sensitive afferents neurons and nitric oxide]. / Etude de l'effect gastroprotecteur d'un pansement antiacide chez le rat. Rôle des prostaglandines endogènes, des neurones afférents sensibles à la capsaïcine et du monoxyde d'azote.

UNLABELLED: The aims of this study were: a) to demonstrate the gastroprotective effect of the antacid and mucosal coating agent Gastralgine (aluminium hydroxide and glycinate, magnesium trisilicate and simeticone) against ethanol- and indomethacin-induced gastric injury in the rat; b) to investigate whether gastroprotection elicited by this agent involves stimulation of capsaicin sensitive afferent neurons and activation of the nitric oxide system. METHODS: Rats received intragastrically 2 mL of the antacid or distilled water followed 1 hr later by 2 mL of 100% ethanol ig or 30 mg of indomethacin sc. The surface of ethanol-induced lesions and the length of indomethacin-induced lesions were measured. The role of afferent neurons and endogenous nitric oxide in the prevention of ethanol-induced gastric damage was determined using respectively capsaicin and the inhibitor of nitric oxide biosynthesis, NG-nitro-L-arginine. RESULTS: The antacid and mucosal coating agent significantly reduced the area of macroscopic lesions induced by ethanol and the length of lesions induced by indomethacin. Both functional ablation of afferent nerves and inhibition of nitric oxide synthesis significantly increased ethanol-induced gastric injury but failed to reverse the gastroprotective effect of the antacid against 100% ethanol. CONCLUSIONS: The antacid and mucosal coating agent Gastralgine has a gastroprotective effect against ethanol- and indomethacin-induced injury in the rat. This property does not involve stimulation of capsaicin sensitive afferent neurons or synthesis of endogenous nitric oxide.

[Cibenzoline versus propafenone by the oral route for preventing recurrence of atrial arrhythmia: multicenter, randomized, double-blind study]. / Cibenzoline versus propafénone par voie orale dans la prévention de la récidive des arythmies auriculaires: étude multicentrique randomisée réalisée en double aveugle.

This multicentre, randomized, double-blind study, conducted in parallel groups, was designed to compare the efficacy and safety of cibenzoline (C) and oral propafenone (P) in the prevention of recurrent atrial arrhythmias (M) over a 6-month period. Patients of either sex with reduced atrial fibrillation or flutter and predominantly in sinus rhythm (> 50%), with a left ventricular shortening fraction greater than or equal to 20% and not receiving any antiarrhythmic treatment were included. Patients presenting severe conduction disorders, severe heart failure (NYHA class III or IV), marked hypotension or recent myocardial infarction were not included. Treatments were administered at the dosage of one tablet twice a day, i.e. 260 mg/day of cibenzoline or 600 mg/day of propafenone. This dosage was reduced by one half in elderly patients (> 70 years). Patients were seen on inclusion (Dzero), and at the third and sixth months or in the case of recurrence of symptoms. Recurrent arrhythmias were assessed by ECG and 24-hour Holter monitoring and according to the symptoms experienced by the patients. Sixty-five patients, 36 men and 29 women, between the ages of 34 to 86 years and presenting an atrial arrhythmia-atrial fibrillation (80%) or atrial flutter (20%)-were included in the trial: 34 patients received cibenzoline and 31 received propafenone. The arrhythmia had already been treated in 78% of cases. Its aetiology was related to hypertensive heart disease (32%), valvular heart disease (8%), other (17%) or idiopathic (43%). The arrhythmia was symptomatic in 91% of patients on inclusion. The ultrasonographic left ventricular shortening fraction was 32.8 +/- 8.1% in group C and 32.6 +/- 6.4% in group P. The two groups were comparable before treatment. The efficacy of the two treatments was comparable: no significant difference in the number of recurrences was demonstrated: 11 patients treated with C and 12 patients treated with P; cumulative percentages of patients without recurrence with good tolerance of treatment (Kaplan-Meier acturial curves) at 6 months were 55.9% with C and 48.4% with P(NS); probability of no recurrence at 6 months (0.63 +/- 0.09 in group C and 0.57 +/- 0.09 in group P); mean time to recurrence (53.4 +/- 44.3 days in group C and 61.6 +/- 35.3 days in group P). Adverse events leading to discontinuation of treatment occurred in 4 patients from each group, and one proarrhythmic effect at 6 months in a patient in group P. The treatments were well tolerated in the majority of cases: there was no significant difference in the number of patients presenting at least one adverse event: 9(26.5%) in group C, 11(35.5%) in group P. Most events were considered to be mild or moderate. The effects of the two treatments on the course of blood pressure, heart rate, PR interval and QT interval calculated at 3 and 6 months compared to DO were not statistically different. The QRS interval increased to a significantly greater extent in group C that in group P (p = 0.02 at 3 months; p = 0.0005 at 6 months). No significant difference was observed between the two groups for the course of laboratory parameters at 3 and 6 months compared to DO in the patients present at these three visits. Cibenzoline can therefore constitute a good alternative to propafenone in the prevention of symptomatic recurrences of atrial tachyarrhythmias. The preferential use of one or other treatment can be guided by individual factors, including tolerance.

[Antiaggregant effect and tolerance of calcium carbasalate administrated immediately after aorto-coronary bypass. Results of a double-blind versus placebo study]. / Efficacité Antiagrégante et tolérance du carbasalate calcique administré dans les suites immédiates des pontages aorto-coronaires. Résultats d'une étude réalisée en double aveugle versus placebo.

The patency of aorto-coronary bypasses is greatly influenced by platelet aggregability, and there is an associated risk of thrombosis which may occur very early during surgery. It is in this context that aspirin has been the subject of successful clinical studies. When administering aspirin, it is preferable to choose formulations that are well tolerated by the gastro-intestinal tract. This was the reason for carrying out the present randomised single-centre double-blind parallel-group study aimed at confirming the platelet anti-aggregant effect and tolerability of calcium carbasalate administered during the immediate postoperative period. The dose prescribed was equivalent to aspirin 325 mg daily, and was given as a single dose 6 hours after the end of the operation and repeated for 7 days, versus placebo, in 56 patients undergoing aorto-coronary bypass grafts. A clinical assessment, ECG, platelet count and measurements of CPK and CPK-MB were carried out daily for the 7 days of the study. Tests of platelet aggregation (to arachidonic acid, ADP and collagen), assays of serum thromboxane B2, MDA and PDF, and urinary assays for beta-thromboglobulin and 6-keto-PGF-1 were carried out before treatment, then 1 and 7 days after the start of treatment. Fifty males (89%) and 6 females, mean age 58.3 years, received treatment with either calcium carbasalate (group C, n = 28) or placebo (group P, n = 28). The atheromatous lesions present in most cases represented triple-vessel disease (37 cases), and most operations were triple bypasses (23 cases) or double bypasses (20 cases). A significant reduction in platelet aggregation to arachidonic acid and collagen on D1 (p = 0.05) and D7 (p < 0.001), and to ADP on D7 (p < 0.01) was observed in group C as compared with group P. Group C also showed significant reductions as compared with group P in respect of serum thromboxane B2 levels on D1 (p < 0.01) and D7 (p < 0.001) and MDA levels on D1 and D7 (p < 0.001). No significant difference was demonstrated between the two groups in respect of urinary 6-keto-PFG-1 excretion. The number of patients showing a rise in CPK was lower in group C but this difference did not reach statistical significance. ST segments change were comparable in the two groups, and no patient complained of anginal pain during the study. These results show that calcium carbasalate administered at a dose equivalent to 325 mg aspirin daily caused very early inhibition of platelet aggregation, specifically inhibiting platelet production of thromboxane B2 without altering prostacyclin levels. In addition, calcium carbasalate was found to be well tolerated. This study confirms the value of early administration of aspirin at a dose of 325 mg daily during the hours immediately following aorto-coronary bypass graft surgery.

Comparison of effects of calcium carbasalate and aspirin on gastroduodenal mucosal damage in human volunteers.

Calcium carbasalate is a therapeutically active salicylate which seems to cause less gastroduodenal mucosal damage than aspirin in laboratory animals. This endoscopist-blinded, randomised, cross over trial aimed to compare acute gastric mucosal damage in 20 healthy volunteers treated with acetyl salicylic acid (ASA) (650 mg three times daily) and effervescent calcium carbasalate (ECC) (826.8 mg three times daily) bioequivalent to 650 mg ASA over a five day period. Endoscopy was performed immediately before treatment and on day 5 of each treatment. Serum salicylate, thromboxane B2, and gastric mucosal prostaglandin E2 (PGE2) concentrations were measured after endoscopy. ECC caused fewer gastric mucosal erosions than ASA. The total number of gastric erosions was 23.8 (16.1) in the ASA treated subjects compared with 9.1 (8.7) in ECC treated subjects (p = 0.004). Differences between ASA and ECC were significant for both the gastric antrum and body, and for both haemorrhagic and non-haemorrhagic erosions. The mean gastric body Lanza score for mucosal damage was lower after ECC than ASA (p = 0.003). The visual analogue score for gastric body damage was lower for ECC (16.9 mm (15.9)) than for ASA (32.7 mm (20.8)), p = 0.008. Serum salicylate concentrations were similar after both preparations (ASA: 66 (23) mg/l, versus ECC: 58 (17) mg/l, NS). Serum thromboxane B2 was similarly reduced using both preparations-97.2 (3.5)% inhibition with ASA, 95.2 (5.5)% inhibition with calcium carbasalate (NS). Suppression of gastric mucosal PGE2 synthesis was similar with both preparations (ASA: 83.4 (17.1)%; ECC 84.3 (12.9)%; NS). It is concluded that ECC causes significantly less gastroduodenal mucosal damage than ASA administered at bioequivalent doses as judged by serum salicylate, serum thromboxane, and mucosal PGE2 values. ECC may therefore be a less harmful alternative treatment to plain ASA.

[Comparative effects of cibenzoline and hydroquinidine in the prevention of auricular fibrillation. A randomized double-blind study]. / Effets comparés de la cibenzoline et de l'hydroquinidine dans la prévention de la fibrillation auriculaire. Une étude randomisée en double aveugle.

The objective of this study was to compare the efficacy and safety of cibenzoline (130 mg twice a day) and sustained-release hydroquinidine (300 mg twice a day) in the prevention of recurrent atrial fibrillation (AF). This randomized double-blind study was conducted in 87 patients, with a mean age of 62 years, presenting with a history of AF for 72 hours to a maximum of 3 years. After restoration of sinus rhythm, in order for the subjects to be included in the study, echocardiography had to reveal a left ventricular shortening fraction of more than 20%. Patients were followed for one year by clinical examination, ECG and 24-hour Holter monitoring performed 7 days after inclusion, then after 3, 6, 9 and 12 months. The two groups, treated with either cibenzoline (n = 40) or hydroquinidine (n = 44), were comparable. The AF recurrence rates with cibenzoline or hydroquinidine were 34.9% had 36.4% at 6 months, and 41.9% and 43.2% at 12 months, respectively (NS). Most recurrences occurred during the first month. Adverse effects were reported in 10 patients (23.3%) with cibenzoline and 12 patients (27.3%) with hydroquinidine. They led to discontinuation of treatment in 6 patients (14%) treated with cibenzoline and 5 patients (11.4%) treated with hydroquinidine. Serious adverse events included one death from hypoglycaemic coma and one case of persistent ventricular tachycardia with hydroquinidine. In conclusion, oral cibenzoline demonstrated the same antiarrhythmic activity as hydroquinidine in the long-term prevention of recurrent atrial fibrillation, with a similar degree of safety. This drug can therefore constitute an alternative to conventional antiarrhythmics in this context.

[Calcium carbasalate-metoclopramide combination versus dihydroergotamine in the treatment of migraine attacks]. / Association carbasalate calcique-métoclopramide versus di-hydroergotamine dans le traitement de la crise de migraine.

In this randomised, double-blind, cross-over study the association of calcium carbasalate+metoclopramide was compared with oral dihydroergotamine mesilate in the treatment of migraine attacks. 155 patients suffering from migraine, with or without aura were analysed; the main efficacy criteria being the evolution of the headache intensity: disappearance of headache 2 hours after administration or incomplete improvement (severe to moderate headache reduced to slight headache). There was a significantly greater reduction in headache intensity following administration of CSC-METO (p < 0.001), the percentage of patients showing recovery or improvement two hours after administration being 64.5% with CSC-METO compared to 43.5% with DHE. A significantly more marked improvement following administration of CSC-METO was also observed for nausea, photophobia, phonophobia, use of analgesic treatment, impact on normal activities and overall assessment by the patient and physician. The frequency of undesirable events was weak and identical for both treatments.

Cibenzoline versus flecainide in the prevention of paroxysmal atrial arrhythmias: a double-blind randomized study.

In a randomized, double-blind, parallel clinical trial, the authors tested and compared flecainide and cibenzoline, a new antiarrhythmic drug, on atrial arrhythmias. Sixty-eight patients (36 men, 32 women, mean age 62.5 +/- 1.6 years) with documented symptomatic paroxysmal atrial arrhythmias (fibrillation in 56, flutter in 12) were recruited and received either cibenzoline 260 mg/day (n = 33) or flecainide 200 mg/day (n = 35). Patients were assessed with physical examination, resting ECG, 24-hour ambulatory ECG recording, two-dimensional echocardiography, and standard biologic titrations before the inclusion day, and 3 months and 6 months after the randomization day. Sixteen patients were withdrawn (7 were lost to follow-up, 7 had side effects, 2 had another medical event). Seventeen patients had documented recurrence of atrial arrhythmia (9 in the cibenzoline group, 8 in the flecainide group) during the study. The efficacy of cibenzoline and flecainide for preventing recurrence of atrial arrhythmias was not significantly different (62.5% versus 71.4%). Eleven patients complained of one or more side effects (cibenzoline, n = 6; flecainide, n = 5), justifying leaving the trial in 6 cases (cibenzoline, n = 3; flecainide, n = 3). Two ventricular proarrhythmic effects were observed. No atrial proarrhythmic effects were reported. The efficacy of cibenzoline and flecainide for preventing atrial arrhythmia is good and similar during a follow-up period of 6 months. In view of these results, cibenzoline may be administered first to prevent atrial arrhythmia.

[Comparative study of the efficacy and tolerability of 2 modalities of intravenous cibenzoline administration in the reduction of recent spontaneous atrial arrhythmia]. / Etude comparative de l'efficacité et de la tolérance de deux modalités d'administration de la cibenzoline intraveineuse dans la réduction des arythmies auriculaires spontanées et récentes.

This multicentre, single blind, parallel group study compared the efficacy and clinical and electrocardiographic tolerance of a 2 minute intravenous administration of cibenzoline at a dose of 1.2 mg.kg-1 with that of a 10 minute 1.75 mg.kg-1 infusion in patients presenting with spontaneous atrial fibrillation (AF) for less than 6 weeks. Sixty-two patients (40 men and 22 women) with an average age of 62 years and presenting with sustained AF for at least 30 minutes with a ventricular rate greater than or equal to 80 bpm were randomly assigned to groups and received via the intravenous route either one of the two treatments. Efficacy (return to sinus rhythm) was assessed by an ECG recording every 5 minutes and at 45 and 60 minutes thereafter. Sixty-one of the 62 randomised patients were assessed for efficacy. Cibenzoline, administered in the form of a bolus or infusion, proved effective within one hour in 4 patients in each group (13%) and arrhythmia persisted with ventricular rate of less than 80 bpm in 10 (33%) and 5 (16%) of the patients respectively. In patients in whom sinus rhythm was not restored, ventricular rate was significantly reduced by cibenzoline. The patients in whom normal rhythm was restored under one of these treatment regimens were significantly younger. Patients in whom rhythm returned to normal following the administration of the bolus had AF of significantly more recent onset than that of the patients in whom abnormal rhythm persisted, whilst the history of the AF did not differ significantly between these two types of response after the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Single infusion of intravenous cibenzoline in the treatment of supraventricular tachyarrhythmias following heart surgery. A double-blind placebo-controlled parallel study.

The efficacy and safety of a single infusion of cibenzoline, a class I antiarrhythmic drug, were assessed in 86 patients presenting with a supraventricular tachyarrhythmia following heart surgery in a placebo-controlled double-blind parallel study. Cibenzoline was effective in 13 patients (30%) vs three patients (6.9%) with placebo (P < 0.05). In the non-converted patients, ventricular rate was significantly slowed by cibenzoline (P < 0.05), which also significantly increased the duration of QRS and QT intervals. Transient adverse events were seen in nine patients receiving cibenzoline: moderate hypotension, sweating, right bundle branch block. One patient with decreased left ventricular function had an increased ventricular rate and QRS duration associated with hypotension. There were no severe adverse events. These results suggest that cibenzoline is effective for the treatment of postoperative supraventricular tachyarrhythmias in patients without impairment of ventricular function.

[Injectable and oral cibenzoline in the treatment of supraventricular tachycardia related to intranodal reentry or accessory atrioventricular conduction pathway]. / Etude de la cibenzoline injectable et orale dans le traitement des tachycardies supraventriculaires liées à une rentrée intranodale ou à une voie de conduction auriculo-ventriculaire accessoire.

Cibenzoline, a Vaughan-Williams Class I antiarrhythmic agent, was studied in 26 patients with orthodromic supraventricular tachycardia (SVT) by nodal reentry (n = 10) or an accessory pathway (AP) (n = 16). IV cibenzoline accelerated sinus rhythm, prolonged PR, AH, HV and QT, widened QRS and depressed or blocked anterograde and retrograde conduction in the accessory pathway, significantly, without significantly modifying conduction capacity in the AV node, nor atrial, nodal or ventricular refractory periods. It converted 6/10 of nodal reentries and 9/16 of reentries due to an AP, by a mean dose of 1 mg/kg, in 2 to 3 minutes, in 12 cases out of 16 by blocking retrograde conduction in the reentry circuit. It prevented reinduction of 12 of the 26 cases of SVT, significantly slowing the cycle of induced SVT in other patients. Oral cibenzoline (260 to 390 mg/day) prevented induced SVT in 11 cases out of 25 and spontaneous SVT in 14 cases out of 26, with a follow-up of 11 +/- 4 months (6 to 16), and this regardless of the reentry mechanisms. Intravenous cibenzoline was not associated with any clinical or hemodynamic intolerance but there was facilitation of episodes of SVT in one patient. Oral administration caused only one case of digestive intolerance, leading to lowering of the dose. Plasma levels showed no significant differences between successes and failures, for both the injection and oral formulations of cibenzoline, whether in terms of the conversion or prevention of episodes. Electrophysiological investigations had a 60% positive and 50% negative predictive value, a sensitivity of 64% and a specificity of 50%. Cibenzoline thus appears to be useful for the conversion and prevention of episodes, SVT, regardless of the reentry circuit, and seems justified, in view of its good safety/acceptability, as first line treatment in this diagnostic indication, measurement of plasma levels and electrophysiological investigations being of little apparent value in terms of guiding treatment and predicting its results.

[Value of cibenzoline in the preventive treatment of recurrent atrial arrhythmia]. / Intérêt de la cibenzoline dans le traitement préventif des arythmies auriculaires récidivantes.

Cibenzoline is a Vaughan-Williams class I anti-arrhythmic with properties intermediate between subclasses IA and IC which limit the incidence of proarrhythmic effects. These specific properties of the drug facilitate the prescription of cibenzoline in cardiology, particularly for the prevention of recurrent atrial arrhythmia: fibrillation, flutter, atrial tachycardia. This study demonstrates that cibenzoline is effective in these indications, since only 23% of the patients had relapsed after 6 months. This efficacy, combined with the good tolerance of the treatment, makes it possible to recommend the prescription of cibenzoline as a first-line treatment for the prevention of atrial arrhythmia. It represents an effective and safe option.

[Study of the efficacy and tolerability of oral administration of cibenzoline in the prevention of recurrence of symptomatic atrial fibrillation]. / Etude de l'efficacité et de la tolérance de la cibenzoline administrée par voie orale dans la prévention des récidives de fibrillation auriculaire symptomatique.

The efficacy and safety of oral cibenzoline were evaluated in 42 patients aged 67 +/- 7 (55-80) and with recurrent symptomatic atrial fibrillation for at least a year and for which at least one previous anti-arrhythmic agent had been stopped for inefficacy or intolerance. Cibenzoline was administered for 6 months at the dose of 260 to 390 mg per day in patients aged under 70, with the possibility of reducing this dose in those aged over 70. Clinical, electrocardiographic and 24-hour Holter evaluation took place at inclusion and after 3 and 6 months' treatment or at the time of trial termination for documented recurrence (atrial arrhythmia persisting for 60 seconds or more). The mean duration of atrial fibrillation was 5.6 +/- 5 years (1-26). It was related to ischemic (22%), valvular (17%), hypertensive (17%), hypertrophic (7%) or dilated (7%) heart disease. No etiology was found in 45% of cases. All patients had taken at least one anti-arrhythmic agent in the past (mean of 2 drugs, range 1 to 6). All patients were symptomatic, the commonest symptoms being palpitations (82%), chest pain (28%), feelings of vertigo (11%) or episodes of acute dyspnea (9%). Thirteen patients (31%) had a documented recurrence (> 60 seconds) during the six months of the trial. Recurrence occurred during the first months of treatment in the majority of patients (11 out of 13). The number of symptomatic patients decreased considerably during treatment with cibenzoline, with the disappearance of palpitations in 83% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Combination of oral administration of cibenzoline and digoxin in patients with supraventricular arrhythmia]. / Association de la cibenzoline et de la digoxine administrées par voie orale chez des patients ayant une arythmie supraventriculaire.

Chronic co-administration of digoxin and several antiarrhythmic drugs increases digoxin plasma levels. To determine the effects of the administration of oral cibenzoline on digoxin plasma levels and its effects on clinical and electrocardiographic parameters, we conducted a prospective multicenter study in 22 cardiac patients with a mean age of 66 +/- 12 years (39-85), who were on long term digoxin therapy (0.25 mg once daily for at least 2 weeks) and who required oral cibenzoline therapy in the prevention of recurrence of symptomatic atrial tachyarrhythmias. Cibenzoline was given for 4 weeks at a dose of 130 mg twice daily in patients aged less than 70 years (group I, n = 15) and this dosage was reduced by half in patients over 70 years of age (group II, n = 7). Evaluation of the effects of this combination on clinical and electrocardiographic tolerability as well as the drawing of blood samples for assay of cibenzoline and digoxin took place before and after 4 weeks treatment with cibenzoline. The digoxin plasma levels were (mean +/- sem) 0.96 +/- 0.1 ng.ml-1 before cibenzoline administration and remained unchanged after 4 weeks of combination therapy (1.0 +/- 0.1 ng.ml-1), p > 0.05. Digoxin plasma levels in group I varied from respectively 0.8 +/- 0.1 ng.ml-1 (0.5-1.7) to 0.8 +/- 0.1 ng.ml-1 (0.4-1.5) and in group II from 1.2 +/- 0.2 ng.ml-1 (0.6-2) to 1.4 +/- 0.3 ng.ml-1 (0.7-2.5). This therapy was well tolerated in 16 patients out of 21 evaluable patients (76%) and there was no significant change in vital signs during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of the efficacy/tolerability ratio of cibenzoline and propafenone in the treatment of ventricular arrhythmia]. / Comparaison du rapport efficacité/tolérance de la cibenzoline et de la propafénone dans le traitement des arythmies ventriculaires.

Cibenzoline (C) was compared with propafenone (P) in 18 adult patients (7 women and 11 men) aged 50 +/- 7 in double-blind, placebo-controlled crossover trial. After a therapeutic wash-out period corresponding to 5 times the half-life of previous anti-arrhythmic drugs, patients with more than 100 premature ventricular contractions (PVC) per hour in two 24 hour Holter records obtained at an interval of 7 days were treated in succession and after randomised by C (390 mg/day in 3 divided doses) and P (900 mg/day in 3 divided doses) for a period of two weeks, each active sequence being followed by a two week wash-out period. Efficacy (based upon the decrease in PVC/hour in a 24 hour Holter) and tolerability were evaluated at the end of each sequence, with samples drawn at the same times for assay of the study drugs. Three patients dropped out of the trial, 1 with each active drug (for epigastric pain) and 1 with dummy. No significant difference was seen between the two drugs regarding the decrease in the total number of PVC/hour in the 15 patients completing the cross-over protocol. A reduction in PVC/hour of more than 70 per cent was seen in 7 patients with C and in 9 patients with P. C was better tolerated than P on the basis of both clinical and electrocardiographic parameters. One patient developed troublesome adverse reactions with C as compared with 4 patients in the case of P. A more than 20 per cent increase in QRS was seen in 7 patients with C and in 10 patients with P, the figures for PR being 2 and 6 patients respectively. One patient showed a proarrhythmic effect with P. Plasma levels of C were significantly higher in responders (328 +/- 149 ng/ml) than in non-responders (137 +/- 41 ng/ml, p less than 0.05). No significant difference was found concerning plasma levels of P (578 +/- 477 ng/ml compared with 646 +/- 457 ng/ml, p greater than 0.05). In conclusion, the efficacy/tolerability ratio in this population with a low risk of serious rhythm events appeared to be better with C than with P.