A study published in the Journal of the American College of Cardiology has found that prolonged QTc is associated with a significantly increased risk of stroke, indicating that drugs that prolong QTc may need to be investigated for a potential association with stroke.
Elsayed Soliman (Epidemiological Cardiology Research Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, USA) and others reported that, according to some data, 38% to 71% of patients with acute stroke have prolonged QTc. They added: “Autonomic dysregulation caused by overactivity of the sympathetic nervous system during acute stroke has been suggested as one of the potential mechanisms. Nevertheless, it is also possible that in some cases, prolonged QTc actually existed before the development of stroke and its presence during the acute phase reflects its common presence in individuals at risk; hence, it could be used as a marker for future stroke.” Therefore, using data from the REGARDS (Reasons for geographic and racial differences in stroke) study, Soliman et al examined the association between risk of stroke and presence of prolonged QTc. The REGARDS study is supported by the National Institute of Neurological Disorders and Stroke, National Institutes of Health.
Of a total study population of 27, 411 participants, 740 (2.7%) had prolonged QTc at the study baseline and 608 (2.2%) developed a stroke in the 8.2 years of follow-up. Soliman et al wrote: “The risk of stroke in study participants with prolonged QTc was almost three times the risk in those with normal QTc (p<0.0001).” They added that the risk of stroke remained significantly high even after adjusting for baseline demographics, traditional stroke risk factors, and QT-prolonging drugs.
Additionally for every one standard deviation increase in QTc, there was a 24% increase in the risk of incident stroke (p<0.0001). According to Soliman et al, the mechanism by which QTc is predictive of incident stroke is not entirely clear at this stage. It is possible that QTc represents a marker of silent undetected atherosclerotic vascular disease.
Soliman et al stated that their findings “add further concern regarding the consequences of QTc prolongation. In addition to increased cardiovascular morbidity and mortality, stroke seems to be another serious outcome.” In their view, the combination of their study’s results and the fact that the use of QTc prolonging drugs is increasing may mean that a study investigating the risk of stroke with QTc prolong drugs is necessary.
They explained that in the PALLAS study, which showed that patients with permanent atrial fibrillation receiving dronedarone (Multaq, Sanofi Aventis) to be at increased risk of stroke compared with those on placebo, there was a 8±40ms increase in QTC duration in the dronedarone group vs. 2±38ms increase in the placebo group (p<0.001) one month after treatment. However, they noted that it was not clear how many of the strokes in patients receiving dronedarone could be explained by the drug’s prolonging QTC effects. Notably, another study (ATHENA) showed dronedarone to be associated with a lower risk of stroke compared with placebo, as Soliman et al commented in their article. Soliman told Cardiac Rhythm News: “Whether the difference in outcomes between PALLAS and ATHENA was due to the type of atrial fibrillation studied (PALLAS reviewed permanent and ATHENA reviewed paroxysmal) or the differences in QTc prolongation need further investigation.”
He said: “Based on our results, QTc duration could be a useful addition to the components of the already existing stroke risk prediction models, which will be our next investigation. Nevertheless, with the increasing number of QTc prolonging drugs in the market, investigating the risk of stroke associated with these drugs seem to be a more urgent task”. Soliman added that in an additional analysis using REGARDS study data, there was 19% increase in the risk of stroke in patients taking QTc prolonging drugs compared with those not taking these drugs (p=0.059), but this needs to be investigated further in a study designed specifically to address this question.