Practice Update: Cardiology

EDITOR’S PICKS 4

Sudden cardiac death: pharmacotherapy and proarrhythmic drugs JACC: Clinical Electrophysiology Take-home message • The authors of this retrospective study examined death certificates and autopsy information for 1363 individuals in Denmark who experienced sudden cardiac death (SCD). The study objective was to determine if exposure to specific drug therapy increased risk for SCD. The cohort’s median age at death was 38 years, and 786 (58%) had been exposed to one or more drugs in the 90 days before death. Analgesic, antihypertensive, and antibiotic drugs were the most commonly used in the cohort. Importantly, a higher risk for sudden arrhythmic death syndrome (SADS) was identified with exposure to drugs classed as “brugadogenic” or drugs with QT-prolonging properties than with explained SCD (OR, 2.16 for brugadogenic and 2.91 for QT-prolonging). • The results of this study indicate that “brugadogenic” and QT-prolonging drugs are associated with an increased risk for SADS. The authors recommend better identification of individuals at risk for arrhythmias as a strategy for lowering rates of SCD.

Abstract OBJECTIVES This study sought to describe the use of pharmacotherapy in a nationwide cohort of young patients with sudden cardiac death (SCD). BACKGROUND Several drugs have been associ- ated with an increased risk of SCD and sudden arrhythmic death syndrome (SADS). It remains unclear how pharmacotherapy may contrib- ute to the overall burden of SCD in the general population. METHODS This was a nationwide study that included all deaths that occurred between 2000 and 2009 and between 2007 and 2009 in people age 1 to 35 years and 36 to 49 years, respectively. Two physicians identified all SCDs through review of death certificates. Autopsy reports were collected. Pharmacotherapy prescribed within 90 days before SCD was identified in the Danish Registry of Medicinal Product Statistics. RESULTS We identified 1,363 SCDs; median age was 38 years (interquartile range: 29 to 45 years), and 72% (n = 975) were men. Autopsy was per- formed in 55%. Overall, 58% of SCD cases (n = 786) received at least 1 drug within 90 days before death. The most common drugs were analgesic drugs (n = 239; 18%), antihypertensive drugs (n = 234; 17%), and antibiotic drugs (n = 218; 16%). After multivariable adjustment, prescription of “brugadogenic” drugs or >1 QT-prolonging drug was associated with an increased risk of SADS compared with explained SCD (odds ratio: 2.16 [95% confidence interval: 1.12 to 4.17] and 2.91 [95% confidence interval: 1.46 to 5.81], respectively). CONCLUSIONS Pharmacotherapy was identified in 58% of the SCD cases. After multivariable adjustment, there was a 2- and 3-fold increased risk of SADS compared with explained SCD in patients receiving brugadogenic drugs or >1 QT-prolonging drug, respectively. Identification of high-risk patients is warranted to lower the burden of SCD. Sudden cardiac death: pharmacotherapy and proarrhythmic drugs: a nationwide cohort study in Denmark. JACC Clin Electrophysiol 2017 May 05;[EPub Ahead of Print], B Risgaard, BGWinkel, R Jabbari, et al.

COMMENT By Raymond L. Woosley MD, PhD T he study by Risgaard, et al pro- vides reinforcing evidence for a strong connection between sudden cardiac death (SCD) in the general pop- ulation and the use of medicines known for their potential to induce arrhythmias. The fact that over 135 medications (www. CredibleMeds.org) in use today result in QT prolongation, a proven independent predictor of sudden cardiac death, has long suggested that such an association might exist. This study has demonstrated that use of these QT-prolonging drugs in a general population is associated with a threefold higher risk for SCD. Likewise, the more than 20 drugs known to induce arrhythmias in patients with Brugada syn- drome (www.brugadadrugs.org) were associated with a twofold higher risk for

SCD. It is remarkable that this risk, long associated with the elderly, is promi- nent in a relatively young population under age 50. The international trend of increasing use of prescription medicines comes with a need for greater aware- ness of their potential harm and the use of modern technology, such as risk factor surveillance and clinical decision-support systems, to reduce that harm.

Dr Woosley is founding President and Chairman of the Board for CredibleMeds Worldwide, a non-profit organization dedicated to safe use of

medications. He is Emeritus Professor of Medicine and Pharmacology at the University of Arizona College of Medicine.

PRACTICEUPDATE CARDIOLOGY