Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?

Jorge E. Romero, Samuel H. Baldinger, David Goodman-Meza, Krysthel Engstrom, Carolina R. Valencia, Anjani Golive, Francisco Medrano, Sabarivinoth Rangasamy, Mohammed Makkiya, John Devens Fisher, Jay N. Gross, Andrew K. Krumerman, Soo G. Kim, Mario J. Garcia, Luigi Di Biase, Kevin J. Ferrick

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. Methods: Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. Results: We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3 %) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7 %, p <0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3 %, respectively). However, the agents most commonly associated with TdP were furosemide (39.3 %), methadone (27 %), SSRIs (19.1 %), amiodarone (18 %), and dofetilide (9 %). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95 % confidence interval [CI] 5.4–524, p <0.001), dofetilide (OR = 25, CI 6.47–103.16, p <0.001), voriconazole (OR = 21.40, CI 3.24–124.25, p <0.001), verapamil (OR = 10.98, CI 2.62–44.96, p <0.001), sotalol (OR = 12.72, 1.95–82.81, p = 0.008), methadone (OR = 9.89, CI 4.05–24.15, p <0.001), and SSRI (OR = 2.26, CI 1.10–5.96, p <0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. Conclusion: Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalJournal of Interventional Cardiac Electrophysiology
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2016

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Therapeutic Equipoise
Torsades de Pointes
Urban Population
Methadone
Vulnerable Populations
Pharmaceutical Preparations
Odds Ratio
Confidence Intervals
Amiodarone
Serotonin Uptake Inhibitors
Multivariate Analysis
Furosemide
HIV Infections
Sotalol
Precipitating Factors
Azithromycin

Keywords

  • Methadone
  • Prolonged QT
  • Torsades de pointes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Drug-induced torsades de pointes in an underserved urban population. Methadone : is there therapeutic equipoise? / Romero, Jorge E.; Baldinger, Samuel H.; Goodman-Meza, David; Engstrom, Krysthel; Valencia, Carolina R.; Golive, Anjani; Medrano, Francisco; Rangasamy, Sabarivinoth; Makkiya, Mohammed; Fisher, John Devens; Gross, Jay N.; Krumerman, Andrew K.; Kim, Soo G.; Garcia, Mario J.; Di Biase, Luigi; Ferrick, Kevin J.

In: Journal of Interventional Cardiac Electrophysiology, Vol. 45, No. 1, 01.01.2016, p. 37-45.

Research output: Contribution to journalArticle

Romero, Jorge E. ; Baldinger, Samuel H. ; Goodman-Meza, David ; Engstrom, Krysthel ; Valencia, Carolina R. ; Golive, Anjani ; Medrano, Francisco ; Rangasamy, Sabarivinoth ; Makkiya, Mohammed ; Fisher, John Devens ; Gross, Jay N. ; Krumerman, Andrew K. ; Kim, Soo G. ; Garcia, Mario J. ; Di Biase, Luigi ; Ferrick, Kevin J. / Drug-induced torsades de pointes in an underserved urban population. Methadone : is there therapeutic equipoise?. In: Journal of Interventional Cardiac Electrophysiology. 2016 ; Vol. 45, No. 1. pp. 37-45.
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title = "Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?",
abstract = "Background: Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. Methods: Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. Results: We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3 {\%}) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7 {\%}, p <0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3 {\%}, respectively). However, the agents most commonly associated with TdP were furosemide (39.3 {\%}), methadone (27 {\%}), SSRIs (19.1 {\%}), amiodarone (18 {\%}), and dofetilide (9 {\%}). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95 {\%} confidence interval [CI] 5.4–524, p <0.001), dofetilide (OR = 25, CI 6.47–103.16, p <0.001), voriconazole (OR = 21.40, CI 3.24–124.25, p <0.001), verapamil (OR = 10.98, CI 2.62–44.96, p <0.001), sotalol (OR = 12.72, 1.95–82.81, p = 0.008), methadone (OR = 9.89, CI 4.05–24.15, p <0.001), and SSRI (OR = 2.26, CI 1.10–5.96, p <0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. Conclusion: Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.",
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author = "Romero, {Jorge E.} and Baldinger, {Samuel H.} and David Goodman-Meza and Krysthel Engstrom and Valencia, {Carolina R.} and Anjani Golive and Francisco Medrano and Sabarivinoth Rangasamy and Mohammed Makkiya and Fisher, {John Devens} and Gross, {Jay N.} and Krumerman, {Andrew K.} and Kim, {Soo G.} and Garcia, {Mario J.} and {Di Biase}, Luigi and Ferrick, {Kevin J.}",
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TY - JOUR

T1 - Drug-induced torsades de pointes in an underserved urban population. Methadone

T2 - is there therapeutic equipoise?

AU - Romero, Jorge E.

AU - Baldinger, Samuel H.

AU - Goodman-Meza, David

AU - Engstrom, Krysthel

AU - Valencia, Carolina R.

AU - Golive, Anjani

AU - Medrano, Francisco

AU - Rangasamy, Sabarivinoth

AU - Makkiya, Mohammed

AU - Fisher, John Devens

AU - Gross, Jay N.

AU - Krumerman, Andrew K.

AU - Kim, Soo G.

AU - Garcia, Mario J.

AU - Di Biase, Luigi

AU - Ferrick, Kevin J.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. Methods: Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. Results: We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3 %) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7 %, p <0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3 %, respectively). However, the agents most commonly associated with TdP were furosemide (39.3 %), methadone (27 %), SSRIs (19.1 %), amiodarone (18 %), and dofetilide (9 %). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95 % confidence interval [CI] 5.4–524, p <0.001), dofetilide (OR = 25, CI 6.47–103.16, p <0.001), voriconazole (OR = 21.40, CI 3.24–124.25, p <0.001), verapamil (OR = 10.98, CI 2.62–44.96, p <0.001), sotalol (OR = 12.72, 1.95–82.81, p = 0.008), methadone (OR = 9.89, CI 4.05–24.15, p <0.001), and SSRI (OR = 2.26, CI 1.10–5.96, p <0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. Conclusion: Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.

AB - Background: Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. Methods: Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. Results: We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3 %) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7 %, p <0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3 %, respectively). However, the agents most commonly associated with TdP were furosemide (39.3 %), methadone (27 %), SSRIs (19.1 %), amiodarone (18 %), and dofetilide (9 %). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95 % confidence interval [CI] 5.4–524, p <0.001), dofetilide (OR = 25, CI 6.47–103.16, p <0.001), voriconazole (OR = 21.40, CI 3.24–124.25, p <0.001), verapamil (OR = 10.98, CI 2.62–44.96, p <0.001), sotalol (OR = 12.72, 1.95–82.81, p = 0.008), methadone (OR = 9.89, CI 4.05–24.15, p <0.001), and SSRI (OR = 2.26, CI 1.10–5.96, p <0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. Conclusion: Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.

KW - Methadone

KW - Prolonged QT

KW - Torsades de pointes

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