Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France

Authors

  • Mariam Molokhia,

    1. Non-Communicable Disease Epidemiology UnitLondon School of Hygiene & Tropical MedicineKeppel Street, WC1E 7HT London, UK
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  • Atul Pathak,

    1. Service de Pharmacologie Clinique du CHU de ToulouseCentre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, EA 3696 Pharmacoepidemiology unit, Université Paul Sabatier37 allées Jules Guesde, Toulouse, France
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  • Maryse Lapeyre-Mestre,

    1. Service de Pharmacologie Clinique du CHU de ToulouseCentre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, EA 3696 Pharmacoepidemiology unit, Université Paul Sabatier37 allées Jules Guesde, Toulouse, France
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  • Laetitia Caturla,

    1. Service de Pharmacologie Clinique du CHU de ToulouseCentre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, EA 3696 Pharmacoepidemiology unit, Université Paul Sabatier37 allées Jules Guesde, Toulouse, France
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  • Jean Louis Montastruc,

    1. Service de Pharmacologie Clinique du CHU de ToulouseCentre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, EA 3696 Pharmacoepidemiology unit, Université Paul Sabatier37 allées Jules Guesde, Toulouse, France
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  • L'Association Française des Centres Régionaux de Pharmacovigilance (CRPV),

    1. Non-Communicable Disease Epidemiology UnitLondon School of Hygiene & Tropical MedicineKeppel Street, WC1E 7HT London, UK
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  • Paul McKeigue

    1. Public Health Sciences, The University of Edinburgh Medical School, Teviot Place Edinburgh EH8 9AG
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Dr Mariam Molokhia, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Tel: +44 0 207 927 2633
Fax: +44 0 207 580 6897
E-mail: mariam.molokhia@lshtm.ac.uk

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Drug-induced long-QT syndrome (LQTS) is a potentially fatal condition that has led to a number of postmarketing withdrawals in recent years.

• However, many cases may not survive long enough to reach hospital, and only a small proportion are reported to pharmacovigilance agencies.

• The extent to which genetic determinants of susceptibility to LQTS are specific to particular drugs, or common to several classes of drug, remains to be determined.

WHAT THIS STUDY ADDS

• We estimated population prevalence of drug-induced LQTS in the Midi-Pyrenees region, southwest France, using five different institutions and assessed feasibility of tracing potential cases (in addition to pharmacovigilance data), using hospital data and rigorous case definition.

• These methods can be adapted to a wider region, used to augment pharmacovigilance reporting, and offer researchers the opportunity to study genetic susceptibility to drug-induced LQTS.

AIMS

The aim of this study was to investigate the incidence and reporting rate of drug-induced long-QT syndrome (LQTS) in France [defined by evidence of torsades de pointes (TdP), QT prolongation and exposure to a relevant drug] and to assess feasibility of case collection for drug-induced LQTS.

METHODS

A retrospective population-based study was carried out in Southwest France in five institutions: three main hospitals, one private clinic and one cardiac emergency unit, searched from 1 January 1999 to 1 January 2005 (population coverage of 614 000). The study population consisted of 861 cases with International Classification of Diseases-10 diagnostic codes for ventricular tachycardia (I147.2), ventricular fibrillation (I149.0) and sudden cardiac death (I146.1) from hospital discharge summaries, supplemented by cases reported to national or regional pharmacovigilance systems, and voluntary reporting by physicians, validated according to internationally defined criteria for drug-induced LQTS.

RESULTS

Of 861 patients coded with arrhythmias or sudden cardiac death, there were 40 confirmed surviving acquired cases of drug-induced LQTS. We estimated that the incidence of those who survive to reach hospital drug-induced LQTS is approximately 10.9 per million annually in France (95% confidence interval 7.8, 14.8).

CONCLUSIONS

Many cases of drug-induced LQTS may not survive before they reach hospital, as the reporting rate for drug-induced LQTS identified through the cardiology records and also reported to pharmacovigilance systems for the Midi-Pyrenees area is 3/40 (7.5%). Using the methods outlined it is possible to assemble cases to study genetic susceptibility to drug-induced LQTS and adapt these methods more widely.

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