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 |
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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. |
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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. 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.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.872</identifier><identifier>PMID: 28117887</identifier><language>eng</language><publisher>England: American College of Clinical Pharmacology</publisher><subject>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</subject><ispartof>Journal of clinical pharmacology, 2017-07, Vol.57 (7), p.924-930</ispartof><rights>2017, The American College of Clinical Pharmacology</rights><rights>2017 American College of Clinical Pharmacology</rights><rights>2017, The American College of Clinical Pharmacology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-b8822c71c6e3eba53ab5bed307198ed052cccf41069bdc246e0095c78c6f1e73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcph.872$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcph.872$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28117887$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Durante‐Mangoni, Emanuele</creatorcontrib><creatorcontrib>Parrella, Antonio</creatorcontrib><creatorcontrib>Vitrone, Martina</creatorcontrib><creatorcontrib>Rago, Anna</creatorcontrib><creatorcontrib>Pafundi, Pia Clara</creatorcontrib><creatorcontrib>Nigro, Gerardo</creatorcontrib><creatorcontrib>Utili, Riccardo</creatorcontrib><creatorcontrib>Russo, Vincenzo</creatorcontrib><title>Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><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.</description><subject>Aged</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral drugs</subject><subject>arrhythmia</subject><subject>Bradycardia</subject><subject>Bradycardia - chemically induced</subject><subject>Cardiac arrhythmia</subject><subject>Cohort Studies</subject><subject>direct antiviral agents</subject><subject>Electrocardiography</subject><subject>Female</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Humans</subject><subject>Interferon</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Risk Factors</subject><subject>sofosbuvir</subject><subject>Sofosbuvir - adverse effects</subject><subject>Sofosbuvir - therapeutic use</subject><subject>Syncope</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0cFq3DAQBmBRWpptUugTFEEvPdSJRrZl-bg4225DoDkEehS2PI611VquJCfs20dLtj3kpEH6GEbzE_IJ2CUwxq92eh4vZcXfkBWUJc8KwYq3ZMVYDRmvGDsjH0LYMQaiKOE9OeMSoJKyWhHcWNTRu3k8BOOsezC6tXTdP6IPSDfDkF4DdQO9Nj6VdK2jmR7oeorm0fjWBmometdGg1Nyv00caTN6NxlNtzin-2gCbS7IuyFZ_Hg6z8n99819s81uf_342axvM52XOc86KTnXFWiBOXZtmbdd2WGfswpqiT0rudZ6KICJuus1LwSmH5a6kloMgFV-Tr6-tJ29-7tgiGpvgkZr2wndEhRIAQJkASLRL6_ozi1-SsMpqFnNC8ZkntTnk1q6PfZq9mbf-oP6t78Evr2AJ2djWtkfuzyhVyO2No4KmDrGo47xqBRP4tmJG4uH_-1eO3XT3G2P_hkECY7F</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Durante‐Mangoni, Emanuele</creator><creator>Parrella, Antonio</creator><creator>Vitrone, Martina</creator><creator>Rago, Anna</creator><creator>Pafundi, Pia Clara</creator><creator>Nigro, Gerardo</creator><creator>Utili, Riccardo</creator><creator>Russo, Vincenzo</creator><general>American College of Clinical Pharmacology</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201707</creationdate><title>Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C</title><author>Durante‐Mangoni, Emanuele ; 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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. 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.</abstract><cop>England</cop><pub>American College of Clinical Pharmacology</pub><pmid>28117887</pmid><doi>10.1002/jcph.872</doi><tpages>7</tpages></addata></record> |
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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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