September/October 2022

Medication Monitor: Risks of Common Drug Use
By Joan Kapusnik-Uner, PharmD, FCSHP, FASHP
Today’s Geriatric Medicine
Vol. 15 No. 5 P. 8

Study Highlights Need for Medication Decision Support for Older Adults

Geriatricians know how challenging it is to manage polypharmacy in their patients. Designing a tolerated regimen is an ongoing challenge that includes titrating different medications, eliminating redundant therapies, deprescribing, ensuring patient adherence, and starting drugs when new conditions emerge. This process is a time-consuming but essential part of the practice.

Given the fact that more than one-half of Medicare beneficiaries are taking 11 or more medications, according to a recent study, medication decision support at the point of care can play an important role in helping prescribers more efficiently maximize regimen efficacy and assess risk in order to avoid adverse reactions.

A recent study published in Drugs – Real World Outcomes highlights this fact while raising safety concerns for geriatric patients about some common short- and long-term noncardiac medications due to their association with a dangerous risk of QT prolongation and torsade de pointes (TdP), a type of tachycardia that can lead to cardiac arrest.

The study, authored by researchers from the National Library of Medicine and FDB (First Databank), is based on an analysis of 1.2 million Medicare claims and more than 5 million patient years of follow-up. The findings demonstrate that utilizing a continuously updated and curated medication decision support system not only is more efficient in helping geriatricians manage polypharmacy risks but also can help protect patient safety.

The QT Prolongation Challenge
QT-prolonging medications associated with TdP are well known, and many drugs have been pulled from the market or their labeling has been changed due to these adverse events. One such drug, hydroxychloroquine, however, received temporary emergency authorization from the FDA in early 2020, as it was hypothesized to be one of the few effective treatments against COVID-19. Once it was found to be largely ineffective to treat the virus and a contributor to TdP, the authorization was later revoked.

Our 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,” finds hydroxychloroquine is not the only noncardiac drug linked with an increased risk of QT prolongation and TdP. Nearly all—14 out of 17 common antibiotic, antidepressant, antinausea, and antiplatelet drugs and other drugs studied—were found to be associated with an increased risk of cardiac arrhythmia and sudden death in older patients.

During hospitalizations, it is easier to assess QT prolongation risks where physiologic monitoring devices, predominately ECGs, are used to survey for such adverse events. However, this is not always practical because the patient needs to be connected to the device during the arrhythmias, which are often transient. Moreover, identifying long QT syndrome based on an ECG is challenging given that, in one study, only 62% of arrhythmia experts and less than 25% of cardiologists and noncardiologists were correct in their diagnoses based on ECG reviews. Risk of QT-prolonging drugs is further increased for patients who are not in a hospital, which makes conducting medication reviews and utilizing medication decision support systems even more crucial within outpatient settings. If the system presents data about patient-specific risk factors as well as contextual clinical information at the point of care, this insight can help clinicians more easily identify older adults who require therapy switches or closer monitoring (eg, blood testing for electrolytes) to prevent adverse events and potentially save lives.

More Than 200% Greater Risk
Our study is the largest of its type that we could find, more than twice as large as a 2005 analysis of noncardiac QT-prolonging drugs. The more recent study eliminated from analysis medications that were pulled from the market due to high risk of drug-induced QT prolongation and TdP or because of low use.

In addition, this analysis of the large cohort of Medicare data included both short- and long-term therapy durations. The short-term (or short-course therapy) drugs were three fluoroquinolone antibiotics (ciprofloxacin, levofloxacin, and moxifloxacin, analyzed individually), three macrolide antibiotics (azithromycin, clarithromycin, and erythromycin, analyzed individually), one antifungal (fluconazole), and one antiemetic (ondansetron).

Nine long-term or chronic usage drugs (also known as maintenance drugs) were also analyzed. They were two selective serotonin reuptake inhibitor antidepressants (citalopram and escitalopram), three antipsychotics (haloperidol, thioridazine, and chlorpromazine), two antiplatelet agents (cilostazol and anagrelide), one antirheumatic drug (hydroxychloroquine), and one anti-Alzheimer’s disease drug (donepezil). Amoxicillin was the control drug. The most common short-term drug taken among the population studied was azithromycin (35%) and citalopram was the most common chronic condition medication (6%). The three most commonly observed proarrhythmic comorbidities among the older adults were ischemic heart disease (28.3%), hypothyroidism (20.7%), and chronic kidney disease (19.1%).

Significant increases in risks were found in both short- and long-term medication usage, and our paper showed some risk variation between current users and former users of many drugs. Most significantly, of the short-term drugs, ondansetron increased the risk of a cardiac adverse event by 205% compared with never users while fluconazole increased the risk by 123% also compared with patients who never used the drug. Older adults who used levofloxacin had a 51% increased risk of cardiac arrhythmia or sudden death compared with those who never used the drug, 63% compared with former users, and 51% of the amoxicillin control group. Erythromycin had an increased risk of 63% compared with never users and the control group and 95% compared with former users.

Although many of the short- and long-term drugs studied can be administered in a hospital setting where closer monitoring is feasible, they are also taken at home, which raises the risk of undetected QT prolongation and TdP. Given the high level of polypharmacy among older adults, it’s likely no surprise to the geriatricians that more than three-quarters (77%) of older adults with Medicare and Medicaid have multiple chronic conditions, as do nearly two-thirds (63%) with Medicare Advantage coverage and 59% of patients with Medicare only. This is important, as QT prolongation risk is known to be additive or cumulative across multiple drugs and other risk factors.

For the maintenance medications, current users of both antiplatelet drugs had a 156% increased risk of arrhythmia or sudden death compared with those who had never used the medications. Hydroxychloroquine showed an increased risk of 68% when compared with patients who never used the drug but no significant difference when compared with former users. Current users of both antidepressants studied showed increased risks, except if the patients had been taking the medication for more than a year. Older adults who were prescribed the antipsychotics studied had an increased risk of 118% compared with patients who never received the drug.

Sex, age, and race also seemed to influence the risk of ventricular arrhythmias and/or sudden death. For both short- and long-term drugs, female sex reduced risk by approximately 30% and younger patients also had a lower risk for both types of medications. Black patients had a 13% higher risk for short-term and 22% higher risk with the long-term drugs, while a lower income also increased risk for both sets of medications. Unsurprisingly, comorbidities, such as proarrhythmic conditions (except for hyperthyroidism for the short-term drugs), as well as hypertension, diabetes, and anemia were risk factors for short- and long-term drugs.

How Medication Decision Support Helps
With new evidence continuously generated about drug reactions, even the most diligent clinician can find it difficult to stay abreast of the latest guidelines. That’s why medication decision support systems are even more essential to help identify at-risk patients based on their histories and status. A tool is even more important given the industry shift to more telehealth and remote patient monitoring and less frequent hospitalizations.

Medication decision support tools can help lessen the burden for geriatricians practicing in hospitals and ambulatory settings in determining these patient safety risks. In addition to providing up-to-date drug evidence, these tools can also analyze patient-specific data within the EHR to identify patients who have a higher risk, eg, patients taking multiple noncardiac drugs with QT prolongation risk and those with congenital history of long QT syndrome, as well as comorbidities such as hypokalemia and cardiac conditions. Workflow integration, however, is key so these medication reviews can be easily performed and interpreted at the point of care in an office or the bedside.

Although medication decision support systems are helpful, they are no replacement for clinical judgment. In some cases, a potentially QT-prolonging medication may be the best therapy available given the patient’s status, comorbidities, current medication list, and other factors.

This study demonstrates that medication decision support systems can help clinicians make such case-by-case decisions and care plans with more complete, timely, and accurate information. If the patients are hospitalized, for example, that knowledge can ensure they receive appropriate monitoring, if applicable. If it is an ambulatory visit, insight from the decision support can drive patient education so they have a full understanding of their risks and benefits. Regardless, medication decision support can help geriatricians prescribe with confidence to protect the health and safety of their patients while addressing their specific care needs and achieving their goals.

— Joan Kapusnik-Uner, PharmD, FCSHP, FASHP, is vice president of clinical content for FDB, which provides drug and medical device knowledge that helps health care professionals make precise decisions. She’s one of the authors of “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.”