Managing drug-induced QT prolongation in clinical practice

Abstract

Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a 'corrected QT' (QTc) value. Normal QTc intervals are typically <450 ms for men and <460 ms for women. For every 10 ms increase, there is a ~5% increase in the risk of arrhythmic events. When prescribing drugs associated with QT prolongation, three key factors should be considered: patient-related risk factors (eg, female sex, age >65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.

Keywords: Adverse events; Cardiology; Clinical pharmacology; Pacing & electrophysiology; Therapeutics.

Figure 1

Measurement of the QT interval.

Figure 2

Non-linear relationship in the estimated rate of patients being free of cardiac events at 40 years of age and QT interval corrected for heart rate (QTc). The study included 647 patients from families with long-QT syndrome divided into four quartiles based on QTc interval. ‘Cardiac events’ were defined as the occurrence of syncope, cardiac arrest or sudden death, and these increased non-linearly with increasing QTc. Data were extracted from a Kaplan–Meier survival graph presented in Priori et al (2003) using WebPlotDigitizer v3.9.

Figure 3

Management of QT prolongation in practice.