Comorbidities and use of proarrhythmic drugs in patients with torsade de pointes arrhythmia

Abstract Introduction Drug-induced long QT interval syndrome (LQTS) is a risk factor for torsade de pointes (TdP) ventricular arrhythmia. Combining several QT-prolonging drugs can also increase risk. Clinical decision support systems (CDSS) can help prescribers assess the risk for TdP associated with drugs. Use of combination of drugs and prevalence of other risk factors is not fully known in TdP . Purpose To describe 1) comorbidities (risk-diagnoses) 2) dispensed prescription drugs and their risk for TdP (risk-drugs) using two different CDSS. The hypothesis was that individuals with TdP had risk-diagnoses and used risk-drugs. Personalized decision regarding risk stratification and medication is important to prevent TdP. Methods Patients with first episode of TdP (ICD-10 I472.C) in the National Patient Register (NPR) between 2006 and 2018 were included in this retrospective register-based cohort study. Comorbidities within 5 years prior to the hospital care episode and at the time of TdP diagnosis were retrieved. Mortality was analyzed (National Cause of Death Register). Medications dispensed within 90 days prior to TdP were retrieved (Swedish Prescribed Drug Register). Drugs were classified using 2 different CDSS (Credible Meds and Janusmed Risk Profile). Individual medication data linked with Janusmed Risk Profile gave a risk score of combination of drugs according to an algorithm. Results 762 patients with TdP were identified, most were elderly (72% ≥65 years old), 50% females. After TdP, 31 patients (4.1%) died within 7 days, 61 (8.0%) within 30 days, 87 (11%) within 90 days. Five years prior to TdP 338 patients (44%) had ≥1 risk-diagnosis (heart failure, cardiomyopathies, acute/ chronic coronary syndromes, renal failure,liver disease, LQTS, ventricular arrhythmia and/or cardiac arrest). More males vs. females had risk-diagnoses (28% vs. 22%, p<0.0015). A median of 6 drugs (IQR 2-9) were dispensed. Anti-depressants and antiarrhythmics were the most common risk-drugs. According to Credible Meds, 192 (25%) patients used ≥1 drug with known risk, 51 patients (6.7%) ≥1 drug with possible risk and 208 patients (27%) ≥1 drug with conditional risk only. 470 patients (62%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (known or possible risk). Another 88 patients had ≥1 risk-diagnosis and/or ≥1 risk-drug (conditional risk). Thus, 558 patients (73%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (Credible Meds). Analysis of combination of drugs showed that 290 patients (38 %) had drugs with increased risk, 547 patients (72%) had ≥1 risk-diagnosis and/or a combined drugs associated with increased risk (Janusmed Risk Profile). Conclusion Prior to TdP approximately a third of patients were dispensed prescription drugs with proarrhythmic risk according to two different CDSS. Almost 75% of patients were dispensed drugs associated with proarrhythmic risk and/or had other proarrhythmic risk factors. Vigilance should be undertaken to modify risk factors to prevent TdP.Baseline characteristicsRisk-drugs dispensed prior to TdP