Sudden cardiac arrest risk of non-cardiac depolarization-blocking drugs

Introduction: Drugs may increase risk of ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac arrest (SCA) in susceptible individuals by blocking cardiac ion channels. This also applies to drugs prescribed for non-cardiac conditions (non-cardiac drugs) if these drugs possess such properties. A well-known example is non-cardiac drugs that block cardiac potassium channels and cardiac repolarization. These drugs may cause excessive QT-interval prolongation and VT/VF in individuals with reduced repolarization reserve (e.g., Long QT syndrome). Similarly, non-cardiac drugs that block cardiac sodium channels and cardiac depolarization increase VT/VF risk in individuals with reduced depolarization reserve (e.g., Brugada syndrome). We hypothesized that non-cardiac depolarization blocking drugs (DB-drugs) are associated with increased VT/VF risk in the general population. Methods and results: A community based case-control study was performed. Cases were out-of-hospital SCA victims with documented VT/VF included in the ARREST study in June 2005-December 2009. Controls were age/sex/SCA-date matched non-SCA individuals from the PHARMO database, which contains complete drug dispensing records from community pharmacies. Multivariate conditional regression analysis was used to assess the association between SCA and non-cardiac DB-drugs. We included 1787 SCA cases (mean age 66 years, 77% male) and matched them to 7666 non-SCA controls. Non-cardiac DB-drugs were used by 81 cases (4.5%) and 249 controls (3.2%), and were associated with a 41% increased SCA risk (ORadj: 1.41 [95% CI: 1.10-1.83] P