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Control of ventricular ectopic beats with intravenous lorcainide maintained by oral doses
383
Control of ventricular ectopic beats with intravenous lorcainide maintained by oral doses R. Terryn ’
Roeselare.
‘, U.W.B.M.
Keulen 2 and W. Amery 3 *
Belgium; -’ Tilburg. The Netherlands;
-’ Beerse. Belgium
We have investigated the feasibility of using oral lorcainide as maintenance therapy for patients with ventricular ectopic beats responsive to initial intravenous injections of lorcainide. Lorcainide is a new antiarrhythmic drug whose actions are thought to be mediated by a specific impairment of fast sodium conductance across myocardial cell membranes [l]. Pharmacological studies have shown activity against reentry phenomena and ectopic pacemaker activity especially in the ventricles [ 11. In the treatment of ventricular premature beats the same high response rate ( f 85%) has been observed with long-term orally administered lorcainide as with single intravenous doses or short-term infusions [2]. We studied 23 patients with a ventricular ectopic beat frequency of at least 15 beats per 5 minutes. Eighteen of them had a history of myocardial infarction. Initially, each patient received two 40-mg intravenous injections of lorcainide separated by a 2-minute interval. This was followed by further 20-mg injections every 2 minutes until the ventricular ectopic beats disappeared, until adverse reactions occurred or to a maximum dose of 180 mg. The doses administered thus ranged from 100 mg to 180 mg with a median of 160 mg. Two subjects failed to respond fully to intravenous lorcainide and were excluded from the subsequent 4-week double-blind study. The remaining 21 patients were randomly allocated to oral treatment with either 100 mg lorcainide twice daily (n = 10) or matching placebo (n= 11). All patients in the lorcainide group completed the 4-week double-blind study period, but 5 of the placebo group were withdrawn after 2 weeks of the study, 3 because of lack of clinical efficacy and 2 because of adverse reactions. At the end of the study, ventricular ectopic beats had almost or completely disappeared in respectively 1 and 9 out of the 10 lorcainide-treated patients. Ventricular ectopic beat suppression in the placebo group was clearly less marked (Fig.). The median ventricular ectopic beat frequency was reduced from 20 beats/5 min (in both groups) to 0 (extremes: O-2) after the lorcainide and 6 (O-20) after the control treatment. The difference between the two groups is significant both regarding the reduction in number of ventricular ectopic beats/5 min (P = 0.02; Mann-Whitney U-test. 2-tailed P) and the percentage reduction in arrhythmic activity (P < 0.0001). No marked changes in systolic or diastolic blood pressure were observed during oral lorcainide or placebo treatment. Adverse reactions were reported by 5 patients in the lorcainide group (gastric pain in 2 cases and sleep disturbances, tremor and anorexia in one case each) and by 6 patients in the placebo group (severe headaches and supraventricular tachycardia with right bundle branch block, causing withdrawal from the treatment of one patient each, and further lethargy (2 patients), sleep disturbances (1) and headache (1)). In conclusion, the present study has clearly demonstrated the efficacy of oral lorcainide (100 mg twice daily) as a successful maintenance therapy for subjects with ventricular ectopic beats responsive to initial treatment with intravenous lorcainide.
* Correspondence Beerse, Belgium.
to: W. Amery,
M.D., Ph.D.. Janssen
International Journal of Cardiology. 3 (1983) 383-384 0 Elsevier Science Publishers B.V.
Pharmaceutics
N.V., Turnhoutseweg,
30, B-2340
tt L1 :
-L
5
1
1
L
P
0%
L
P
L
l-49%
P
L
50-&l%
P
a5 -99 v.
L
P’
lcQ% ,
”
% suppression * L = lorcainide;
Fig. Percentage
suppression
P=
of VEB
placebo
of ventricular
ectopic
beats after oral treatment
with lorcainide
or placebo.
Acknowledgement The authors wish to thank Dr. J. Stillaert (Ieper), Dr. H. Robijns (Sint-Truiden), for their valuable contribution to this cooperaand Dr. G. Verstreken (Bonheiden) tive trial.
References 1 Carmeliet E, Janssen PAJ, Marsboom R, Van Nueten J, Xhonneux R. Antiarrhythmic, electrophysiologic and haemodynamic effects of lorcainide. Arch Int Pharmacodyn Ther 1978:23 1: 104- 130. 2 Amery WK. Heykants JJP, Xhonneux R, Towse G, Oettel P, Gough DA, Janssen PAJ. Lorcainide (R 15 889) a first review. Acta Cardiol 1981;36:207-234.
Control of ventricular ectopic beats with intravenous lorcainide maintained by oral doses R. Terryn ’
Roeselare.
‘, U.W.B.M.
Keulen 2 and W. Amery 3 *
Belgium; -’ Tilburg. The Netherlands;
-’ Beerse. Belgium
We have investigated the feasibility of using oral lorcainide as maintenance therapy for patients with ventricular ectopic beats responsive to initial intravenous injections of lorcainide. Lorcainide is a new antiarrhythmic drug whose actions are thought to be mediated by a specific impairment of fast sodium conductance across myocardial cell membranes [l]. Pharmacological studies have shown activity against reentry phenomena and ectopic pacemaker activity especially in the ventricles [ 11. In the treatment of ventricular premature beats the same high response rate ( f 85%) has been observed with long-term orally administered lorcainide as with single intravenous doses or short-term infusions [2]. We studied 23 patients with a ventricular ectopic beat frequency of at least 15 beats per 5 minutes. Eighteen of them had a history of myocardial infarction. Initially, each patient received two 40-mg intravenous injections of lorcainide separated by a 2-minute interval. This was followed by further 20-mg injections every 2 minutes until the ventricular ectopic beats disappeared, until adverse reactions occurred or to a maximum dose of 180 mg. The doses administered thus ranged from 100 mg to 180 mg with a median of 160 mg. Two subjects failed to respond fully to intravenous lorcainide and were excluded from the subsequent 4-week double-blind study. The remaining 21 patients were randomly allocated to oral treatment with either 100 mg lorcainide twice daily (n = 10) or matching placebo (n= 11). All patients in the lorcainide group completed the 4-week double-blind study period, but 5 of the placebo group were withdrawn after 2 weeks of the study, 3 because of lack of clinical efficacy and 2 because of adverse reactions. At the end of the study, ventricular ectopic beats had almost or completely disappeared in respectively 1 and 9 out of the 10 lorcainide-treated patients. Ventricular ectopic beat suppression in the placebo group was clearly less marked (Fig.). The median ventricular ectopic beat frequency was reduced from 20 beats/5 min (in both groups) to 0 (extremes: O-2) after the lorcainide and 6 (O-20) after the control treatment. The difference between the two groups is significant both regarding the reduction in number of ventricular ectopic beats/5 min (P = 0.02; Mann-Whitney U-test. 2-tailed P) and the percentage reduction in arrhythmic activity (P < 0.0001). No marked changes in systolic or diastolic blood pressure were observed during oral lorcainide or placebo treatment. Adverse reactions were reported by 5 patients in the lorcainide group (gastric pain in 2 cases and sleep disturbances, tremor and anorexia in one case each) and by 6 patients in the placebo group (severe headaches and supraventricular tachycardia with right bundle branch block, causing withdrawal from the treatment of one patient each, and further lethargy (2 patients), sleep disturbances (1) and headache (1)). In conclusion, the present study has clearly demonstrated the efficacy of oral lorcainide (100 mg twice daily) as a successful maintenance therapy for subjects with ventricular ectopic beats responsive to initial treatment with intravenous lorcainide.
* Correspondence Beerse, Belgium.
to: W. Amery,
M.D., Ph.D.. Janssen
International Journal of Cardiology. 3 (1983) 383-384 0 Elsevier Science Publishers B.V.
Pharmaceutics
N.V., Turnhoutseweg,
30, B-2340
tt L1 :
-L
5
1
1
L
P
0%
L
P
L
l-49%
P
L
50-&l%
P
a5 -99 v.
L
P’
lcQ% ,
”
% suppression * L = lorcainide;
Fig. Percentage
suppression
P=
of VEB
placebo
of ventricular
ectopic
beats after oral treatment
with lorcainide
or placebo.
Acknowledgement The authors wish to thank Dr. J. Stillaert (Ieper), Dr. H. Robijns (Sint-Truiden), for their valuable contribution to this cooperaand Dr. G. Verstreken (Bonheiden) tive trial.
References 1 Carmeliet E, Janssen PAJ, Marsboom R, Van Nueten J, Xhonneux R. Antiarrhythmic, electrophysiologic and haemodynamic effects of lorcainide. Arch Int Pharmacodyn Ther 1978:23 1: 104- 130. 2 Amery WK. Heykants JJP, Xhonneux R, Towse G, Oettel P, Gough DA, Janssen PAJ. Lorcainide (R 15 889) a first review. Acta Cardiol 1981;36:207-234.