QTFactors.org: A companion database for use with QTdrugs.org

Issue: June 2018

ByKlaus Romero, MS, MD

ByTyler Gallo, PharmD

ByC. Will Heise, MD

ByRaymond L. Woosley, MD, PhD

ByR. David Woosley, MPH

The QT interval on the ECG is recognized as an independent predictor of cardiac mortality and a sensitive, but relatively nonspecific, predictor of drug-induced torsades de pointes. In recent years, numerous new drugs that have the potential to cause QT prolongation have reached the market. With the development of computerized alerts to inform prescribers when their patients are at risk of excessive QT prolongation, clinicians are becoming acutely aware of the importance of QT monitoring to inform patient care decisions.

The drug labels for more than 85 drugs now include some recommendation for screening or monitoring of QT intervals. In order to prescribe these medicines safely, clinicians are expected to be able to accurately measure and interpret the QT interval. Several studies have documented the need for improvement in physicians’ diagnostic and management skills with regard to QT prolongation. When clinicians encounter a patient with a prolonged QT, optimum management requires consideration of potential contributing factors including the patient’s genetics, electrolytes, clinical history, active medical problems, electrolytes, diet, supplements, hormones and medications.

Raymond L. Woosley, MD, PhD — Raymond L. Woosley

R. David Woosley, MPH — R. David Woosley

The federally funded CredibleMeds.org website was established to foster the safe use of medicines and specifically to curate a publicly available list of the medicines that prolong QT and/or increase the risk for torsades de pointes (TdP). The QTdrugs list, maintained at CredibleMeds.org, now includes more than 150 drugs that prolong QT and 103 that are associated with TdP. This is a 24% increase in the past 2 years. The list is available to more than 112,000 global registrants who access the lists approximately 22,000 times each month. More than 40,000 people have installed the free CredibleMeds smartphone app (iOS, Android or Windows) that allows rapid online access to the QTdrugs lists.

New QTFactors list

To further assist clinicians when interpreting QT intervals in their patients, the CredibleMeds.org website recently released to the public a curated list of the clinical factors that have been associated with QT prolongation or TdP.

Figure 1 is a screenshot for www.QTFactors.org, which can also be reached from the navigation bar at www.CredibleMeds.org. When launched on March 12, the list included 76 factors associated with QT prolongation. The Scientific Review Committee for CredibleMeds analyzes available evidence to identify the clinical and laboratory factors associated with QT prolongation or TdP in humans. A monthly search of PubMed using the search term “QT and Torsad*” is performed and all publications are reviewed for reports of factors associated with increased QT and/or TdP. Newly found factors are added to the database (QTFactors.org) and any evidence for factors already in the database is marked for review and analysis. The committee then grades the quality of evidence as high, moderate, low or very low using a modification of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process. For each factor, the committee determines the strength of the association and quality of the evidence separately for QT prolongation and TdP.

Visitors can search the list for specific terms and use filters to limit displayed factors to those that have evidence with a certain level of quality. The entire list, or a filtered list, can be printed or exported as a PDF or Excel file. For each factor, the website also includes a link that searches PubMed and displays all reports of QT prolongation or TdP associated with it.

Figure 1. Screenshot of www.QTFactors.org, which identifies factors for QT prolongation or torsades de pointes.

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Because the assessed strength of evidence is obviously subjective, based on evidence that is constantly changing and often of variable quality, the CredibleMeds Scientific Review Committee seeks feedback and advice if anyone is aware of additional evidence or disagrees with the committee’s assessment of the evidence. AZCERT is especially interested in learning of factors that might have been overlooked, or if any should be placed in a different subcategory. The webpage for the list includes a feedback button that activates a pop-up to send messages directly to CredibleMed’s Scientific Advisory Committee.

Clinical and research applications

Clinicians faced with a complex patient with prolonged QT may find it helpful to review the list of factors to see if any of the patient’s diagnoses or laboratory findings might be contributing to a prolonged QT. Limiting the search to yield only those factors that have the highest level of evidence can expedite the search. The list may help explain QT prolongation when drugs are not likely to be the cause. For example, QT prolongation in patients with infection or inflammation may be due to the illness and not the patient’s medicines.

For researchers who are developing clinical decision support tools that calculate a risk score to identify patients at risk for excessive QT prolongation or TdP, the QTFactors list provides a comprehensive list that can be used to screen health care databases for those factors that are associated with QT prolongation in a specific population. These factors can be weighted to compute patient-specific risk scores for QT prolongation as part of clinical decision support tools. Several clinical decision support tools that calculate a QT risk score are now in clinical practice and utilize the QTdrugs lists. The QTFactors list is expected to help researchers refine and focus these decision support tools by identifying candidate risk factors for possible inclusion in these QT risk scores.

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For more information:
Raymond L. Woosley, MD, PhD, is professor of medicine and co-director of the Clinical Data Analytics and Decision Support Division in the College of Medicine-Phoenix at the University of Arizona. He is president of AZCERT, the nonprofit sponsor of the CredibleMeds website. Woosley is also a member of the Practice Management and Quality Care section of the Cardiology Today Editorial Board. He can be reached at rwoosley@azcert.org.
Klaus Romero, MS, MD, is director of clinical pharmacology and quantitative medicine at the Critical Path Institute, Tucson, Arizona.
C. William Heise, MD, is assistant professor of medicine, College of Medicine-Phoenix, University of Arizona.
Tyler Gallo, PharmD, is a postdoctoral research associate, College of Medicine-Phoenix, University of Arizona.
R. David Woosley, MPH, is a research assistant at AZCERT.

Disclosure: The authors report no relevant financial disclosures.