Healthy Skepticism Library item: 2283

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Publication type: Journal Article

De Bruin ML, Pettersson M, Meyboom RH, Hoes AW, Leufkens HG.
Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.
Eur Heart J 2005 Mar; 26:(6):590-7
http://eurheartj.oxfordjournals.org/cgi/content/full/26/6/590

Abstract:

AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice.

METHODS AND RESULTS: All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89-1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database.

CONCLUSION: Anti-HERG activity is associated with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines.

Keywords:
MeSH Terms: Adverse Drug Reaction Reporting Systems Aged Anti-Arrhythmia Agents/therapeutic use Arrhythmia/chemically induced* Databases, Factual Death, Sudden/etiology* Female Gender Identity Heart Ventricles Humans Long QT Syndrome/chemically induced Male Middle Aged Odds Ratio Potassium Channel Blockers/adverse effects* Potassium Channel Blockers/blood Potassium Channel Blockers/therapeutic use Potassium Channels, Voltage-Gated/antagonists & inhibitors* Research Support, Non-U.S. Gov't Risk World Health Organization Substances: Anti-Arrhythmia Agents KCNH2 protein, human Potassium Channel Blockers Potassium Channels, Voltage-Gated