JMIR Publications

ABSTRACT

Background:

Drug-induced prolongation of the corrected QT interval (QTc) increases the risk for Torsades de Pointes (TdP) and sudden cardiac death. Medication effects on the QTc have been studied in controlled settings, but may not be well evaluated in real world settings, where medication effects may be modulated by patient demographics and comorbidities as well as the usage of other concomitant medications.

Objective:

We demonstrate a new, high-throughput method leveraging the electronic health records (EHR) and Surescripts pharmacy database to monitor real-world medication QTc prolongation and potential interacting effects from demographics and comorbidities.

Methods:

We included all outpatient ECGs from 9/2008-12/2019 at a large academic medical system that were in sinus rhythm with a heart rate of 40-100 beats per minute, QRS < 120 milliseconds (ms), and QTc 300-700ms by Bazett’s formula. We used prescription information from the Surescripts pharmacy database and EHR medications lists to classify whether a patient was on a medication during an ECG. Negative control ECGs came from patients not currently on the medication but who had been or would be on that medication within 1 year. We calculated the difference in mean QTc between ECGs on and off a medication and made comparisons to known medication TdP risks per the CredibleMeds.org database. Using linear regression, we studied the interaction of patient-level demographics/comorbidities on medication QTc prolonging associations.

Results:

We analyzed the effects of 272 medications on 310,335 ECGs from 159,397 individuals. Medications associated with the greatest QTc prolongation were dofetilide (mean QTc difference 21.52ms 95% CI [10.58,32.70]), mexiletine (18.56 [7.70,29.27]), amiodarone (14.96 [13.52,16.33]), rifaximin (14.50 [12.12,17.13]), and sotalol (10.73 [7.09,14.37]). Several top QT prolonging medication such as rifaximin, lactulose, cinacalcet, and lenalidomide were not previously known but have plausible mechanistic explanations. Significant interactions were observed between demographics/comorbidities and the QTc prolongation of many medications such as coronary disease and amiodarone.

Conclusions:

We demonstrate a new, high-throughput technique for monitoring real-world medication QTc prolongation effects from readily accessible clinical data. Using this approach, we confirmed known medications with QTc prolongation and identified potential new associations and demographic/comorbidity interactions that could supplement findings in curated databases.