Out-of-hospital cardiac arrest: A pharmacoepidemiological approach

Out-of-hospital cardiac arrest (OHCA) is a major public health problem that accounts for 50% of all deaths from cardiovascular causes in Western societies. OHCA is usually caused by cardiac arrhythmias (ventricular tachycardia [VT], ventricular fibrillation [VF]). Numerous factors, often interacting, may increase the risk of cardiac arrhythmias ultimately leading to disruptions in cardiac electrophysiology. These factors include co-morbidities (coronary artery disease, congestive heart failure, diabetes mellitus), genetic factors and drug use. A mechanism by which drugs may cause such disruptions is by blocking cardiac ion channels. The observational studies included in this thesis present novel insights into the role of drugs in the occurrence of OHCA. Part 1 of this thesis presents studies aimed to study whether cardiac repolarization blocking drugs increase the risk OHCA. Our findings show that drugs causing QT-prolongation as off-target effect confer higher OHCA risk than drugs that prolong the QT interval by design. Part 2 presents studies aimed to determine whether depolarization blocking (DB) drugs increase the risk of OHCA. Our findings show that use of non-cardiac DB-drugs is associated with increased risk of OHCA compared with no use of any non-cardiac DB-drugs. Part 3 describes a study aimed to determine whether sulfonylurea drugs (SU-drugs) decreases the risk of OHCA. Our findings show that SU-drugs are associated with reduced OHCA risk compared to metformin monotherapy. Lastly, Part 3 presents a study aimed to investigate a possible association of beta-blockers with non-VT/VF during OHCA. Our findings show that non-selective beta-blocker use, but not β1 selective beta-blocker, are associated with non-shockable rhythm in OHCA.