Common Drugs Associated with Increased Risk for Cardiac Disease, Sudden Death in Elderly Patients

Study finds antibiotics, antidepressants, anti-platelets and other drugs contribute to adverse events and mortality.

Certain types of common antibiotic, antidepressant, anti-nausea and anti-platelet drugs are associated with an increased risk of cardiac arrhythmia and sudden death in older patients, according to a study of Medicare claims data compiled by researchers from the National Library of Medicine (NLM) and FDB (First Databank, Inc.).

The study, “Using Medicare Data to Assess the Proarrhythmic Risk of Non-Cardiac Treatment Drugs that Prolong the QT Interval in Older Adults: An Observational Cohort Study,” was published in the journal Drugs – Real-World Outcomes, which targets research involving the use of real-world data to evaluate health outcomes and inform healthcare decision-making, with a particular focus on healthcare-related big data.

Researchers found 14 of the 17 drugs studied were associated with a higher risk of adverse or fatal outcomes in elderly patients based on analysis of claims data from 1.2 million de-identified Medicare beneficiaries over 5 million patient-years of follow-up.

“Our study shows that there is a definite safety issue with these drugs when prescribed to higher-risk patients such as the elderly, who will likely also require closer monitoring if alternative safer therapies cannot be prescribed,” said Joan Kapusnik-Uner, PharmD, FCSHP, FASHP, vice president of clinical content for FDB. “These findings, based on a deep dive of a large cohort using Medicare claims data, conclude that medication decision support systems that leverage patient-specific risk factors and contextual clinical information could help clinicians identify patients that require therapy switches or closer monitoring to prevent adverse events and save lives.”

Driving Predictive Interventions

Researchers limited their study to non-cardiac drugs with a known risk of QT-prolongation and torsades des pointes (TdP), a type of tachycardia that can lead to cardiac arrest. It was found that although QT prolongation can be measured physiologically, it's an unreliable predictor of the likelihood of evolving into a serious ventricular arrhythmia. This means outcome studies including the measure of sudden death based on large clinical data sets are especially important to assess the risk of drug-induced arrhythmia.

Two types of drug therapies were studied.

The short-term use drugs studied included: three fluoroquinolone antibiotics (ciprofloxacin, levofloxacin, and moxifloxacin, analyzed individually); three macrolide antibiotics (azithromycin, clarithromycin, and erythromycin, analyzed individually); one antifungal (fluconazole); and one anti-emetic (ondansetron). Nine chronic usage drugs (also known as maintenance drugs) were also analyzed: two selective serotonin reuptake inhibitor (SSRI) antidepressants (citalopram and escitalopram); three antipsychotics (haloperidol, thioridazine, and chlorpromazine); two anti-platelet agents (cilostazol and anagrelide); one anti-rheumatic drug (hydroxychloroquine); and one anti-Alzheimer's disease drug (donepezil).

Of the short-term drugs, researchers found the antibiotics levofloxacin increased the risk of cardiac arrhythmia or sudden death by 51% compared to the amoxicillin control, while erythromycin had an increased risk of 63%. The anti-nausea drug ondansetron increased the risk of a cardiac adverse event by 205%, while the antifungal fluconazole increased the risk by 123%.

Drugs taken for chronic conditions also seemed to result in dangerous QT prolongation among older patients, according to the study. Current patients prescribed the antipsychotics showed an increased risk of arrhythmia or sudden death of 118% compared to patients who never received the drug. Similarly, for both of the anti-platelet drugs, current users had an increased risk of 156%, while hydroxychloroquine showed an increased risk of 68% when comparing patient controls. Current users of both SSRI antidepressants studied showed increased risks, except if the patient had been taking the medication for more than a year, which appeared to help mitigate the risk.

“What was notable for us is that these are common, everyday drugs that are widely prescribed and administered in both inpatient and outpatient settings,” Dr. Kapusnik-Uner said. “The results indicate that prescribers may want to reconsider therapies for their higher risk, older patients if they currently include these drugs, especially if they have relevant cardiac comorbidities or electrolyte disturbances. Regardless, considering this is one of the largest studies of its kind, we hope it leads to further study of meaningful changes in patient prescribing that incorporates more clinically relevant evidence combined with patient-specific QT prolongation risk factor information.”

Targeted Medication Warnings

Hospitals and health systems are deploying new medication decision support tools that can help them identify potential medication risks described in this QT prolongation research. FDB Targeted Medication Warnings leverage patient-specific information within the electronic health record to identify patients who have higher risk, so that the resulting clinical guidance is more selective, actionable and presented at the most appropriate time, such as in the prescribing workflow.

This is achieved by pre-screening or considering relevant patient information first—such as patient lab values, clinical risk scores, and others—with the most up-to-date FDB drug knowledge before generating alerts. This approach targets alerts and guidance in a selective and more meaningful way that is also integrated into clinical workflows.