Drug-related hepatotoxicity risk in elderly patients with atrial fibrillation: insights from the nationwide Italian START registry

Atrial fibrillation (AF) patients frequently require polypharmacy, increasing the risk of drug-drug interactions and hepatotoxicity. We analyzed the use of drugs potentially associated with liver injury in anticoagulated AF patients. We applied the LiverTox classification to AF patients from the START registry, categorizing them based on the use of LiverTox A drugs (high risk of liver toxicity). Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95%CIs) for factors associated with the use of these drugs and their impact on liver function tests (LFTs). Median age was 81 years with 46% of women. 8,215 AF patients were taking 40,355 distinct molecules at enrolment, with a median of 5 drugs per patient (IQR 3-7). Overall, 3,416 (41.6%) received at least one LiverTox A drug. These patients were more often male, overweight, smokers, hypertensive, diabetic, with cardiovascular or cerebrovascular history, and on polypharmacy. The most commonly prescribed LiverTox A drugs were statins, amiodarone, and allopurinol, both in the overall population and within subgroups stratified by major cardiovascular conditions. In multivariable logistic regression, among LiverTox A drugs, amiodarone (OR 1.61, 95%CI 1.29-2.00) and methimazole (OR 1.83, 95%CI 1.04-3.03) were associated with elevated LFTs. Among frequently prescribed drugs, warfarin, furosemide, ramipril, lansoprazole, and canrenone were also associated with increased LFTs. Direct oral anticoagulants, compared to warfarin, showed a lower risk of increased LFTs after adjustment for confounders. In conclusion, many AF patients are treated with drugs at high risk of hepatotoxicity.

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Journal
Scientific Reports
Published
2025-12-31
DOI
https://doi.org/10.1038/s41598-025-28502-8
Citations
1
Primary Topic
Atrial Fibrillation Management and Outcomes
Type
article
Field-Weighted Citation Impact
1.39
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article

Drug-related hepatotoxicity risk in elderly patients with atrial fibrillation: insights from the nationwide Italian START registry

Raimondo De Cristofaro, Rita Santoro, Claudio Vasselli, Erica De Candia et al.
1 citations
Scientific Reports
Atrial Fibrillation Management and Outcomes
1.39
article

Drug-related hepatotoxicity risk in elderly patients with atrial fibrillation: insights from the nationwide Italian START registry

Raimondo De Cristofaro, Rita Santoro, Claudio Vasselli, Erica De Candia, Carmine Spataro, Margherita Reduzzi, Simona Pedrini, Alessandra Poz, Francesco Cibecchini, Marcello Di Nisio, Arianna Pani, Anna Falanga, Teresa Lerede, Giovanni Nante, Serena Rupoli, Danilo Menichelli, Antonio Ciampa, Chiara Ambaglio, Vincenzo Oriana, Giovanni Barillari, L. Crippa, Marco Marzolo, Ettore Porreca, Carmelo Paparo, Gianluca Gazzaniga, Marco Cattaneo, Paolo Chiarugi, Elena Lotti, Antonio Insana, Salvatore Bradamante, Valeria Micheli, Vincenza Rossi, Giuliana Martini, L. Ruocco, Catello Mangione, Oriana Paoletti, Walter Ageno, Martina Berteotti, Giacomo Lucarelli, Domenico Lione, Paola Casasco, Podda Gianmarco, Paolo Pedico, Antonietta Piana, Domizio Serra, Dr Alessandra Serrao, Giuseppe Malcangi, Igor Diemberger, Pasquale Pignatelli, Gualtiero Palareti, Monica Vastola, R Lombardi, Maddalena L. Zighetti, Nicola Lucio Liberato, Prof. Daniele Pastori, Benilde Cosmi, Eugenio Bucherini, Giuseppe Boriani, Elvira Grandone, Rossella Marcucci, Vittorio Pengo, Andrea Toma, Simona Pezzella, Luca Bucherini, START2 Registry, Vincenzo Toschi, Sophie Testa, Antonio Chistolini, Giovanna Colombo, Donatella Colaizzo, LiverTox in atrial fibrillation, Emilia Antonucci, Daniela Poli, Doris Barcellona
article en
1 citations

Abstract

Atrial fibrillation (AF) patients frequently require polypharmacy, increasing the risk of drug-drug interactions and hepatotoxicity. We analyzed the use of drugs potentially associated with liver injury in anticoagulated AF patients. We applied the LiverTox classification to AF patients from the START registry, categorizing them based on the use of LiverTox A drugs (high risk of liver toxicity). Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95%CIs) for factors associated with the use of these drugs and their impact on liver function tests (LFTs). Median age was 81 years with 46% of women. 8,215 AF patients were taking 40,355 distinct molecules at enrolment, with a median of 5 drugs per patient (IQR 3-7). Overall, 3,416 (41.6%) received at least one LiverTox A drug. These patients were more often male, overweight, smokers, hypertensive, diabetic, with cardiovascular or cerebrovascular history, and on polypharmacy. The most commonly prescribed LiverTox A drugs were statins, amiodarone, and allopurinol, both in the overall population and within subgroups stratified by major cardiovascular conditions. In multivariable logistic regression, among LiverTox A drugs, amiodarone (OR 1.61, 95%CI 1.29-2.00) and methimazole (OR 1.83, 95%CI 1.04-3.03) were associated with elevated LFTs. Among frequently prescribed drugs, warfarin, furosemide, ramipril, lansoprazole, and canrenone were also associated with increased LFTs. Direct oral anticoagulants, compared to warfarin, showed a lower risk of increased LFTs after adjustment for confounders. In conclusion, many AF patients are treated with drugs at high risk of hepatotoxicity.

Scientific ReportsVol. 15(1)
AOL (United States) (US), University of Padua (IT), University of Cagliari (IT), University of Milan (IT), University of Pavia (IT), Casa Sollievo della Sofferenza (IT), Ospedale di Circolo e Fondazione Macchi (IT), Agostino Gemelli University Polyclinic (IT), Istituto Neurologico Mediterraneo (IT), University of Chieti-Pescara (IT), Ospedale San Paolo (IT), Danubius International University (RO), IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT), Azienda Ospedaliera di Cosenza (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale A. Perrino (IT), Ospedale Papa Giovanni XXIII (IT), Ospedali Riuniti di Ancona (IT), Azienda Unità Sanitaria Locale Della Romagna (IT), Azienda Ospedaliera S.Giuseppe Moscati (IT), Ospedale San Paolo (IT), Alessandro Manzoni Hospital (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Regione Puglia (IT), Presidio Ospedaliero (IT), Ospedale Santa Maria della Misericordia di Udine (IT), A. O. Ordine Mauriziano di Torino (IT), IRCCS Ospedale San Raffaele (IT), Azienda Ospedaliera Universitaria Senese (IT), Ospedale di Parma (IT), Ospedale Regina Margherita (IT), Ospedale Generale Regionale Francesco Miulli (IT), Policlinico Casilino (IT), Azienda Ospedale - Università Padova (IT), Fondazione Poliambulanza Istituto Ospedaliero (IT), Ospedale Santa Maria della Misericordia di Rovigo (IT), Azienda Ospedaliera Pugliese Ciaccio (IT), Ospedale SS. Annunziata (IT), Istituto Nazionale di Fisica Nucleare, Sezione di Roma I (IT), Ospedale Maggiore di Chieri (IT), Azienda Ospedaliera Treviglio (IT), Azienda Ospedaliera Universitaria Pisana (IT), Istituti Ospitalieri di Cremona (IT), University of Bari Aldo Moro (IT), Sapienza University of Rome (IT)
Good health and well-being
Openalex Percentile: Top 12%
Atrial Fibrillation Management and Outcomes
1.39
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