QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

Abstract

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTcprolonging drugs. A statistically nonsignificant increased risk for arrhythmias (OR 1.2, 95% CI 0.8 to 1.9) was observed in patients who received QTc-prolonging drugs. A clearly increased risk of arrhythmias was, however, found in patients with a history of asthma (OR 9.9, 95% CI 1.0 to 100) and in patients using potassiumlowering drugs (OR 5.3, 95% CI 1.1 to. 25.9). Our data do not suggest that there is a strong overall association between the use of QTc-prolonging drugs and hospitalization for cardiac arrhythmias in the population at large. However, there appears to be clinically relevant associations of patients with a history of asthma and patients taking potassium-lowering drugs. The use of QTc-prolonging drugs should therefore be either avoided or monitored closely in these specific patients. ᮊ2003 by Excerpta Medica, Inc.(Am J Cardiol 2003;91:59 -62) C ardiac arrhythmias as an adverse effect of noncardiac drugs has been an issue of growing importance in medical science during the last few years, resulting in regulatory action concerning several drugs. 1 Because of the seriousness of this adverse effect, regulatory action has sometimes already been taken after a few case reports, before the actual risk has been quantified in large population-based studies.For only a few of all QTc-prolonging drugs, studies have unequivocally shown a causal relation between the use of the drugs and the occurrence of cardiac arrhythmias. The use of antihistamines has been associated with an increased risk for cardiac arrhythmias. 2 In contrast, no increased risk for serious rhythm disorders was observed in patients who took cisapride, 3 although its use has been linked to the occurrence of cardiac arrhythmias in several case reports. 4,5 In this population-based study, we evaluated the risk for serious cardiac arrhythmias and the use of several noncardiac QTc-prolonging drugs in day-to-day practice. Subsequently, we focused on several specific groups of patients who may be quite vulnerable to druginduced arrhythmias.

In‐hospital cardiac arrest is associated with use of non‐antiarrhythmic QTc‐prolonging drugs

“…A finding consistent with other studies on the association between QTc-prolonging drugs and cardiac arrhythmias is that there appears to be a positive doseresponse relationship [3,6,[16][17][18][19]. In accordance with Ray et al [20], we found that cytochrome P450 pharmacokinetic drug-drug interactions apparently play an important role.…”

“…A finding consistent with other studies on the association between QTc‐prolonging drugs and cardiac arrhythmias is that there appears to be a positive dose–response relationship [3, 6, 16–19]. In accordance with Ray et al.…”

QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors

“…Furthermore, most studies on drug‐induced QTc prolongation have focused on the risk of QTc prolongation and TdP when using only one QTc‐prolonging drug. It is not known whether combining two or more QTc‐prolonging drugs leads to a cumulative or perhaps even synergistic prolongation of the QTc interval .…”

Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a PotentIKurInhibitor

“…4 The most widely used antiarrhythmic drugs, for example, amiodarone/dronedarone 5 are efficacious but are nonselective and inhibit ion channels, which are expressed in the human atrium and ventricle. Agents that inhibit ion channels that prolong ventricular effective refractory period have the potentially life threatening arrhythmia torsades de pointe, 6 and therefore, administration of nonselective drugs is often limited to a hospital setting with monitoring. There is currently an unmet medical need for agents that effectively restore NSR and have an increased margin for safety for the treatment of AF.…”