Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C

Recently, several cases of symptomatic, sometimes fatal bradycardia during the first days of direct‐acting antiviral (DAA) (eg, sofosbuvir [SOF]) administration have been reported. We analyzed in detail electrocardiographic (ECG) changes during SOF‐ or non‐SOF‐based chronic hepatitis C (CHC) treatme...

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Veröffentlicht in:Journal of clinical pharmacology 2017-07, Vol.57 (7), p.924-930
Hauptverfasser: Durante‐Mangoni, Emanuele, Parrella, Antonio, Vitrone, Martina, Rago, Anna, Pafundi, Pia Clara, Nigro, Gerardo, Utili, Riccardo, Russo, Vincenzo
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container_end_page 930
container_issue 7
container_start_page 924
container_title Journal of clinical pharmacology
container_volume 57
creator Durante‐Mangoni, Emanuele
Parrella, Antonio
Vitrone, Martina
Rago, Anna
Pafundi, Pia Clara
Nigro, Gerardo
Utili, Riccardo
Russo, Vincenzo
description Recently, several cases of symptomatic, sometimes fatal bradycardia during the first days of direct‐acting antiviral (DAA) (eg, sofosbuvir [SOF]) administration have been reported. We analyzed in detail electrocardiographic (ECG) changes during SOF‐ or non‐SOF‐based chronic hepatitis C (CHC) treatment, specifically focusing on bradyarrhythmias. All 39 consecutive patients treated at our center with any interferon‐free regimen between June and December 2015 were included in this study (26 SOF‐based therapy vs 13 no‐SOF interferon‐free regimens). ECG tracings were obtained from all patients the first day of treatment and after 7, 14, and 28 days. ECG parameters (P‐wave, QRS, QT interval, JT interval, Tapex‐Tend interval duration) were compared between the 2 groups at baseline and at the 3 different time points during antiviral therapy. There were no cases of symptomatic bradycardia/syncope. In the SOF group, QTc duration rose after 1 week (from 424.3 to 431.2 milliseconds; P = .013) and returned to baseline during therapy. QT dispersion dropped since week 1 (from 85.6 to 67.2 milliseconds) and remained significantly reduced until the end of the observation period (72.9 msec) (P = .003). JT dispersion reduced up to week 2 (P = .010) and returned to baseline at week 4; in the no‐SOF group, QRS dispersion transiently reduced (from 41 to 34.5 milliseconds, day 7). No other significant changes were observed in the remaining parameters. In CHC patients treated with SOF and other DAAs, ECG parameter changes were mild and/or transient and did not translate into clinically significant electrophysiological effects in the absence of amiodarone coadministration.
doi_str_mv 10.1002/jcph.872
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We analyzed in detail electrocardiographic (ECG) changes during SOF‐ or non‐SOF‐based chronic hepatitis C (CHC) treatment, specifically focusing on bradyarrhythmias. All 39 consecutive patients treated at our center with any interferon‐free regimen between June and December 2015 were included in this study (26 SOF‐based therapy vs 13 no‐SOF interferon‐free regimens). ECG tracings were obtained from all patients the first day of treatment and after 7, 14, and 28 days. ECG parameters (P‐wave, QRS, QT interval, JT interval, Tapex‐Tend interval duration) were compared between the 2 groups at baseline and at the 3 different time points during antiviral therapy. There were no cases of symptomatic bradycardia/syncope. In the SOF group, QTc duration rose after 1 week (from 424.3 to 431.2 milliseconds; P = .013) and returned to baseline during therapy. QT dispersion dropped since week 1 (from 85.6 to 67.2 milliseconds) and remained significantly reduced until the end of the observation period (72.9 msec) (P = .003). JT dispersion reduced up to week 2 (P = .010) and returned to baseline at week 4; in the no‐SOF group, QRS dispersion transiently reduced (from 41 to 34.5 milliseconds, day 7). No other significant changes were observed in the remaining parameters. 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subjects Aged
Antiviral agents
Antiviral Agents - pharmacology
Antiviral drugs
arrhythmia
Bradycardia
Bradycardia - chemically induced
Cardiac arrhythmia
Cohort Studies
direct antiviral agents
Electrocardiography
Female
Hepatitis
Hepatitis C
Hepatitis C, Chronic - drug therapy
Humans
Interferon
Male
Middle Aged
Risk Factors
sofosbuvir
Sofosbuvir - adverse effects
Sofosbuvir - therapeutic use
Syncope
title Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C
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