Efficacy of Disopyramide Phosphate in the Treatment of Refractory Ventricular Tachycardia

Vismara, Louis A.; Vera, Zakauddin; Miller, Richard R.; Mason, Dean T.

doi:10.1016/s0002-9149(77)80218-x

Cited by 67 publications

(12 citation statements)

References 15 publications

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“…The majority of published studies reporting the antiarrhythmic efficacy of disopyramide have used an average dose of 150 mg four times daily,20 23 although some have used lower doses of 100 mg four times daily.24 Although a higher dose of disopyramide could have been chosen for this study, the dose chosen led to unacceptable side effects in 30% of patients that may have increased further had a higher dose range been chosen.…”

Section: Discussionmentioning

confidence: 99%

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

Pratt¹,

Young²,

Francis³

et al. 1984

Circulation

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This placebo-controlled, double-blind, longitudinal crossover study compares the efficacy of disopyramide and ethmozine, a new investigational drug, in suppressing frequent (40 or more per hour) ventricular premature depolarizations (VPDs) in 27 patients completing a 37 day protocol. Although both drugs significantly reduced VPDs relative to placebo, ethmozine was a superior antiarrhythmic drug in achieving near-total abolition of VPDs (30% of patients), which was never observed during disopyramide dosing (p < .05). At the 80% VPD reduction level, ethmozine was effective in 56% of all patients compared with an effectiveness in only 22% of patients during disopyramide therapy (p < .05). The mean peak plasma level of ethmozine was 0.66 + 0.8 gg/ml, which significantly fell to a trough level of 0.1 + 0.08 gg/ml (p < .001). Mean peak and trough plasma levels of disopyramide exhibited less fluctuation (2.6 + 0.9 ,ug/ml vs 2.2 0.9 gg/ml). Ethmozine had no effect on the QTC interval, whereas disopyramide prolonged it significantly. Importantly, while disopyramide produced serious side effects in 30% of patients, ethmozine was well tolerated with no statistically significant side effects compared with placebo. Circulation 69, No. 2, 288-297, 1984. EPIDEMIOLOGIC STUDIES in which 12-lead electrocardiograms have been used have documented an increased risk of sudden cardiac death in patients with coronary heart disease who have ventricular premature depolarizations (VPDs). 1-3 Ambulatory electrocardiographic recording has allowed a more systematic and complete quantification of these ventricular arrhythmias that are predictive of sudden cardiac death, especially in patients surviving myocardial infarction.±7The currently available antiarrhythmic drugs include the /3-blockers, some of which have well-defined efficacy for suppressing VPDs.8'9 A number of multi- 288center clinical trials using /3-blockers for patients in the late-hospitalization phase of acute myocardial infarction have shown an overall reduction of sudden cardiac death. I"2 None of these multicenter trials were designed specifically to define the mechanism of this reduction in sudden cardiac death that presumably was a result of preventing sustained ventricular tachycardia and ventricular fibrillation. MethodsProtocol. This randomized, placebo-controlled, doubleblind, crossover study was performed in 33 patients. The occurrence of .40 VPD/hr on at least two consecutive 24 hr ambulatory electrocardiographic recordings (screening) made up the entry criteria. Of the 33 patients randomized, 27 patients (18 men and nine women, ranging in age from 36 to 72 years) completed the protocol and the data from these patients form the basis of this report. Six patients were dropped from the study. Three of these patients, although having the qualifying arrhythmia during screening (_40 VPD/hr), failed to qualify on placebo monitoring. One patient had chronic heart failure that worsened during placebo and ethmozine dosing and was dropped from the study; invasiv...

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Section: Discussionmentioning

confidence: 99%

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

Pratt¹,

Young²,

Francis³

et al. 1984

Circulation

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“…The effectiveness of intravenous disopyramide in the termination rather than the prophylaxis of ventricular tachycardia (Orning, 1976;Vismara, Vera, Miller & Mason, 1977) has not been widely investigated. When it is clear that disopyramide has been given during tachycardia the success rate of termination has been up to 100% in some series (Mizgala & Huvelle, 1976).…”

Section: Discussionmentioning

confidence: 99%

The effect of intravenous disopyramide phosphate on recurrent paroxysmal tachycardias.

Camm¹,

Ward²,

Spurrell³

1979

Brit J Clinical Pharma

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1 Recurrent paroxysmal atrial, atrioventricular and ventricular tachycardias in 50 patients without acute coronary insufficiency, heart failure or metabolic abnormality were treated with disopyramide phosphate in a dose of 2 mg/kg body weight infused over 5 min. 2 Conversion to sinus rhythm within 10 min of the completed infusion occurred in 10 of 14 (7 1%) patients with paroxysmal 'lone' atrial fibrillation, 3 of 7 (43%) patients with paroxysmal atrial flutter, 6 of 9 (67%) patients with paroxysmal atrial tachycardia, 5 of 9 (56%) patients with paroxysmal atrioventricular tachycardia associated with the Wolff-Parkinson-White syndrome and 8 of 11 (73%) patients with paroxysmal ventricular tachycardia. 3 Side effects: significant systemic hypotension in 3, high grade AV block in 1, an increased ventricular response producing symptoms in 4, post conversion asystole in 1 and sinus bradycardia in 2. 4 The anti-arrhythmic effect and arrhythmogenic side effects may be related to both the direct membrane stabilizing effect and the anticholinergic effect of disopyramide.

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“…maintenance therapy. The rapid initial injection of 2 mg/kg in approximately 5 min was designed to produce a dramatic response in refractory ventricular tachycardia (Vismara et al, 1977) where some risk of toxicity can be accepted. It ought not to be recommended for routine use as a loading dose.…”

Section: Discussionmentioning

confidence: 99%

“…over 10 min may cause hypotension and bradycardia (Ashford, Carmichael and Kidner, 1979). As a compromise between the rapid attainment of consistent effective plasma concentrations and the avoidance of acute toxicity the authors suggest a loading dose of 2 mg/kg, given over 15 min, although the data suggest (Vismara et al, 1977) that even with a simultaneous infusion (0 4 mg/kg/hr) effective plasma concentrations may be lost after 2 hr; and a further smaller bolus dose (1 mg/kg) may be needed to maintain an effective plasma concentration.…”

Section: Discussionmentioning

confidence: 99%

Some cardiovascular problems with disopyramide

Warrington

Hamer

1980

Postgraduate Medical Journal

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Efficacy of Disopyramide Phosphate in the Treatment of Refractory Ventricular Tachycardia

Cited by 67 publications

References 15 publications

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

The effect of intravenous disopyramide phosphate on recurrent paroxysmal tachycardias.

Some cardiovascular problems with disopyramide

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