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ORIGINAL ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 1  |  Page : 11-13

Clinical results of combined amiodarone and mexiletine therapy in refractory ventricular tachycardias


Rajaie Cardiovascular Medical and Research Center; Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Date of Web Publication23-Apr-2019

Correspondence Address:
Dr. Majid Haghjoo
Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Vali-e-Asr St., Ayatollah Hashemi-Rafsanjani Blvd, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_4_19

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  Abstract 


Background: Refractory recurrent ventricular tachycardia is a difficult therapeutic problem. There are implantable cardioverter-defibrillator (ICD) patients with amiodarone-refractory of ventricular arrhythmia (VA) who are not eligible for catheter ablation. The aim of this cohort study was to assess the efficacy of mexiletine in combination with amiodarone in the reduction of VA in this group of patients. Methods: This was a retrospective study of all consecutive ICD patients who were treated by adding mexiletine to amiodarone in refractory electrical storm or frequent VA episodes. The enrolled patients were ineligible for catheter ablation. Results: Thirty-seven patients (32 males; mean age, 57 ± 14 years; range, 26–81 years) were studied. Adding mexiletine to amiodarone had no significant effect on QRS width, QTc interval, and PR interval (all P > 0.05). We observed a significant decrease in the number of total ICD shock and significant increase in appropriate antitachycardia pacing during follow-up after initiating mexiletine. Mexiletine therapy also significantly reduced the amiodarone dose during the follow-up. No mortality was observed in the present cohort during the study period. Conclusions: Mexiletine, when added in case of amiodarone failure, reduces VA episodes and appropriate therapies in patients with an implantable cardioverter defibrillator.

Keywords: Implantable defibrillator, mexiletine, ventricular fibrillation, ventricular tachycardia


How to cite this article:
Madadi S, Nemati M, Fazelifar A, Kamali F, Haghjoo M. Clinical results of combined amiodarone and mexiletine therapy in refractory ventricular tachycardias. Res Cardiovasc Med 2019;8:11-3

How to cite this URL:
Madadi S, Nemati M, Fazelifar A, Kamali F, Haghjoo M. Clinical results of combined amiodarone and mexiletine therapy in refractory ventricular tachycardias. Res Cardiovasc Med [serial online] 2019 [cited 2019 Nov 14];8:11-3. Available from: http://www.rcvmonline.com/text.asp?2019/8/1/11/256881




  Introduction Top


Therapy with implantable cardioverter-defibrillators (ICDs) could improve survival among patients who are at risk of sudden cardiac death.[1] An increasing number of ICD implantation have resulted in an increasing number of surviving years after the episodes of ventricular arrhythmia (VA). The underlying arrhythmia substrate deteriorates over time despite the protection of ICD; electrical storm (ES) is one of them.[2] Refractory recurrent ventricular tachycardia is a difficult therapeutic problem. ES, defined by three or more episodes of ICD shock during 24-h, is an acute arrhythmia emergency problem and is reported to occur in 10%–20% of ICD patients. ES increases total and cardiac mortality.[3],[4],[5]

Antiarrhythmic drugs (AADs) are the initial treatment for these patients. Catheter ablation therapy may not be readily available or may be ineffective and is recommended in the case of the failure of the AADs for ES. Combination of AADs is commonly used in such patients. Amiodarone is the most effective agent, but may be ineffective in some patients.[6],[7],[8] The most effective and safest combination is not known.

The aim of this cohort study was to assess the efficacy of mexiletine in combination with amiodarone in the reduction of VA episodes and appropriate ICD shocks.


  Methods Top


Between October 2009 and October 2015, we retrospectively included all consecutive ICD patients who were treated by mexiletine for amiodarone-refractory VAs for at least 6 months. The enrolled patients were ineligible for catheter ablation. VA refractory to amiodarone was defined as ES (≥3 episode of VAs during 24-h requiring ICD therapy) or recurrent episodes of VAs in a few days. Exclusion criteria were mexiletine intolerance or initiating mexiletine before reaching the maximum dose of amiodarone. Our local Ethical Committee approved this study, and all patients provided written informed consent.

Implantable cardioverter-defibrillator programming

Typical ICD setting for primary and secondary prevention due to VF was as follows: detection criterion for slow VT was 167 bpm and for fast VT and VF zones was 181 bpm and 200 bpm, respectively. For the VT zone, the therapy was set to three times antitachycardia pacing (ATP) followed by four maximum energy shocks. For the VF zone, it was one ATP during charging followed by four maximum energy shocks. These settings were changeable according to the clinical situation with the concern of the electrophysiologist.

Intervention and follow-up

The dose of amiodarone after venous loading was initiated with 200 mg daily, and it was increased gradually up to 400 mg four times a day. In the absence of control VT/VF at the maximum dose of amiodarone, mexiletine was started with 100 mg twice a day and was increased to 200 mg three times a day. Patients were followed up for a mean of 1 year. Heart rate, heart rhythm, blood pressure, QRS morphology, VT morphology, the QT/QTc interval, and heart failure symptoms were checked and recorded in every ICD clinic visit.

The primary endpoint of the study was the total number of episodes of VT/VF requiring ICD therapy during follow-up. The secondary endpoints of the study included mortality, the total number of shocks, the number of appropriate shock, appropriate ATP, ES, and drug discontinuation.

Statistical analysis

Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS) version 21.0 (SPSS, an IBM company). The categorical variables were compared by the Chi-square test or Fisher's exact test. The quantitative variables were presented by the mean ± standard deviation and compared with Student's t-test (paired and unpaired) or with Wilcoxon rank-sum test. P < 0.05 was considered statistically significant. The variables showing a statistically significant difference in the univariate analysis were used to create multivariate binary logistic regression model (stepwise).


  Results Top


Thirty-seven patients (32 males; mean age, 57 ± 14 years; range, 26–81 years) were studied. The demographic characteristics of all patients are summarized in [Table 1]. Adding mexiletine to amiodarone had no significant effect on QRS width, QTc interval, and PR interval (all P > 0.05) [Table 2]. We observed a significant decrease in the number of total ICD shock and significant increase in appropriate ATP during follow-up after initiating mexiletine [Table 3].
Table 1: Baseline patient characteristics

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Table 2: Comparison of electrocardiographic features, renal function, and amiodarone dose before and after initiating mexiletine

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Table 3: Efficacy of mexiletine treatment in controlling ventricular arrhythmias

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To evaluate renal function after prescribing mexiletine, renal function was assessed in all patients. There were no significant change in renal function tests (all P > 0.05) 6 months after initiating mexiletine [Table 2]. However, mexiletine therapy significantly reduced the amiodarone dose during the follow-up. No mortality was observed in the present cohort during the study period.


  Discussion Top


Clustered episodes of VAs are clinically important and difficult to treat. Data on AAD use in patients with an ICD who develop frequent VA events or ES are very limited. Intravenous followed by oral amiodarone together with beta-blocker therapy has been shown to be successful as a short-term management of ES and possibly results in long-term outcomes similar to those in patients not experiencing VA episodes.[9],[10],[11],[12]

A previous report on the combination of mexiletine and amiodarone reported a reduction in VT/VF events, but the two drugs were initiated simultaneously with no control group.[12] A single case of adding mexiletine to amiodarone to terminate an ES was reported, but this is the first study to look at the benefits and safety of mexiletine in a cohort of ICD patients with frequent VA episodes.[11]

This study was a retrospective cohort study for evaluation of the efficacy and safety of adding mexiletine to amiodarone in the reduction of ICD shocks in patients suffering from ES. Most of the previous studies on the efficacy of AADs in patients with an ICD mainly focused on patients who have not yet had therapy from their ICD or just had a few VT/VF events while being treated with an ICD.[6]

In the total cohort of 37 patients, adding mexiletine to Class III and/or other Class I AADs was effective in reducing the number of VT/VF episodes and ICD therapies. In a similar study that was conducted by Gao et al., mexiletine was shown to be effective as an adjutant therapy to amiodarone in reducing the total and appropriate ICD shocks and ES episodes.[9]

OPTIC study (therapy in cardiovascular defibrillator patients) showed that amiodarone was more effective than beta-blockers or sotalol in reducing ICD shock episodes.[7],[12] In CASCADE study (conventional vs. amiodarone drug evaluation), amiodarone was superior to Class I AADs such as procainamide and quinidine in reducing ICD shocks.[13]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Poole JE, Johnson GW, Hellkamp AS, Anderson J, Callans DJ, Raitt MH, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008;359:1009-17.  Back to cited text no. 1
    
2.
Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576-83.  Back to cited text no. 2
    
3.
Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study (CIDS): A randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297-302.  Back to cited text no. 3
    
4.
Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter automatic defibrillator implantation trial investigators. N Engl J Med 1996;335:1933-40.  Back to cited text no. 4
    
5.
Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G, et al. Arandomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter unsustained tachycardia trial investigators. N Engl J Med 1999;341:1882-90.  Back to cited text no. 5
    
6.
Gatzoulis KA, Andrikopoulos GK, Apostolopoulos T, Sotiropoulos E, Zervopoulos G, Antoniou J, et al. Electrical storm is an independent predictor of adverse long-term outcome in the era of implantable defibrillator therapy. Europace 2005;7:184-92.  Back to cited text no. 6
    
7.
Gao D, Van Herendael H, Alshengeiti L, Dorian P, Mangat I, Korley V, et al. Mexiletine as an adjunctive therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia events in patients with an implantable defibrillator. J Cardiovasc Pharmacol 2013;62:199-204.  Back to cited text no. 7
    
8.
Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES, et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: The OPTIC study: A randomized trial. JAMA 2006;295:165-71.  Back to cited text no. 8
    
9.
Dorian P, Newman D, Berman N, Hardy J, Mitchell J. Sotalol and type IA drugs in combination prevent recurrence of sustained ventricular tachycardia. J Am Coll Cardiol 1993;22:106-13.  Back to cited text no. 9
    
10.
Ferreira-González I, Dos-Subirá L, Guyatt GH. Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators: A systematic review. Eur Heart J 2007;28:469-77.  Back to cited text no. 10
    
11.
Manolis AG, Katsivas AG, Vassilopoulos C, Tsatiris CG. Electrical storms in an ICD-recipient with 429 delivered appropriate shocks: Therapeutic management with antiarrhythmic drug combination. J Interv Card Electrophysiol 2002;6:91-4.  Back to cited text no. 11
    
12.
Murata H, Miyauchi Y, Hayashi M, Iwasaki YK, Yodogawa K, Ueno A, et al. Clinical and electrocardiographic characteristics of electrical storms due to monomorphic ventricular tachycardia refractory to intravenous amiodarone. Circ J 2015;79:2130-7.  Back to cited text no. 12
    
13.
Waleffe A, Mary-Rabine L, Legrand V, Demoulin JC, Kulbertus HE. Combined mexiletine and amiodarone treatment of refractory recurrent ventricular tachycardia. Am Heart J 1980;100:788-93.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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