Long-term proarrhythmic pharmacotherapy among patients with congenital long QT syndrome and risk of arrhythmia and mortality

Abstract

Aims It is Class I recommendation that congenital long QT syndrome (cLQTS) patients should avoid drugs that can cause torsades de pointes (TdP). We determined use of TdP risk drugs after cLQTS diagnosis and associated risk of ventricular arrhythmia and all-cause mortality. Methods and results Congenital long QT syndrome patients (1995–2015) were identified from four inherited cardiac disease clinics in Denmark. Individual-level linkage of nation-wide registries was performed to determine TdP risk drugs usage (www.crediblemeds.org) and associated risk of ventricular arrhythmias and all-cause mortality. Risk analyses were performed using Cox-hazards analyses. During follow-up, 167/279 (60%) cLQTS patients were treated with a TdP risk drug after diagnosis. Most common TdP risk drugs were antibiotics (34.1%), proton-pump inhibitors (15.0%), antidepressants (12.0%), and antifungals (10.2%). Treatment with a TdP risk drug decreased 1 year after diagnosis compared with 1 year before (28.4% and 23.2%, respectively, P < 0.001). Five years after diagnosis, 33.5% were in treatment (P < 0.001). Risk factors for TdP risk drug treatment were age at diagnosis (5-year increment) [hazard ratio (HR) = 1.07, confidence interval (CI) 1.03–1.11] and previous TdP risk drug treatment (HR = 2.57, CI 1.83–3.61). During follow-up, nine patients were admitted with ventricular arrhythmia (three were in treatment with a TdP risk drug). Eight patients died (four were in treatment with a TdP risk drug). No significant association between TdP risk drug use and ventricular arrhythmias or all-cause mortality was found (P = 0.53 and P = 0.93, respectively), but events were few. Conclusion Torsades de pointes risk drug usage was common among cLQTS patients after time of diagnosis and increased over time. A critical need for more awareness in prescribing patterns for this high-risk patient group is needed.

When genetic burden reaches threshold

“…Non-genetic factors are known to influence disease risk amongst pathogenic variant carriers in several cardiac diseases, ranging from generic factors such as age and sex to disease-specific modulators (e.g. obesity in HCM 10 and QT prolonging drugs in LQTS 11 ). It is also increasingly recognized that additional genetic factors may act to modulate the phenotype in individuals with a primary pathogenic variant and underlie a substantial proportion of the variability in penetrance and disease severity.…”

QTc Interval-Prolonging Medications Among Patients With Lung Cancer: Implications for Clinical Trial Eligibility and Clinical Care

“…We obtained a list of QTc-prolonging medications from CredibleMeds®, an on-line resource developed and maintained by the Arizona Center for Education and Research on Therapeutics that is frequently cited for its database of QT prolonging drugs, stratified by risk of causing torsade de pointes (see Supplementary Table 1). 22,[29][30][31] Our principal analyses included those medications with known risk of causing Torsades de Pointes (TdP). As defined by CredibleMeds®, these include (1) medications that prolong the QTc interval and are clearly associated with a known risk of TdP, even when taken as recommended; and (2) medications with possible risk of TdP, defined as medications that prolong the QTc interval but currently lack evidence for a risk of TdP when taken as recommended.…”

Out‐of‐hospital cardiac arrest and differential risk of cardiac and non‐cardiac QT‐prolonging drugs in 37 000 cases

“…Unlike antiarrhythmic drugs which are generally prescribed by cardiologists who are aware of their OHCA-risk and have the means to take risk-mitigating precautions [14], non-cardiac QT-prolonging drugs are most often prescribed by noncardiologists who may be less aware of this risk and/or have fewer means to monitor it (e.g., serial ECG); moreover, some drugs are available without prescription [15][16]. A recent study demonstrated that this may even result in prescription of QT-prolonging drugs to patients with a known diagnosis of congenital Long QT syndrome (LQTS) who have a clearly increased risk of TdP and from whom prescription of these drugs should be withheld (Class I recommendation) [17].…”