UF study finds excess use of loop diuretics following initiation of dihydropyridine calcium channel blockers

One in five adults in the United States take dihydropyridine calcium channel blockers to treat hypertension, which have long been viewed as safe and effective. However, one disadvantage of using this type of calcium channel blocker is the risk of leg swelling, or edema. To resolve the swelling, the suggested treatment includes reducing or stopping the calcium channel blocker.

A new study published in JAMA Network Open by University of Florida researchers found a substantial number of patients are being prescribed a loop diuretic for leg swelling induced by calcium channel blocker. Loop diuretics are commonly used to treat edema caused by heart disease. While loop diuretics are used to treat leg swelling from other causes such as calcium channel blocker, a more effective and safer remedy is discontinuation of the calcium channel blocker.

Scott M. Vouri, Ph.D., is the study’s lead author and a clinical assistant professor of pharmaceutical outcomes and policy in the UF College of Pharmacy.

“When I was a geriatric clinical pharmacist, I frequently identified unnecessary loop diuretic use among patients prescribed calcium channel blockers, and this led to preventable adverse events and impacted patients’ quality of life. Treating a drug side effect unnecessarily with another drug, is called prescribing cascade,” said Scott Martin Vouri, Pharm.D., Ph.D., BCGP, the study’s lead author and a clinical assistant professor of pharmaceutical outcomes and policy in the UF College of Pharmacy and the assistant director of pharmacy services with the University of Florida Health Physicians. “Unfortunately, this problematic prescribing is not well documented. Therefore, we planned to quantify the magnitude of this prescribing cascade using a pharmacovigilance approach called prescription sequence symmetry analysis.”

Analyzing data from more than 55,000 adults without heart failure who had a new loop diuretic prescription 360 days before or after calcium channel blocker initiation between 2007 and 2016, the researchers found the loop diuretic was initiated nearly twice as often after calcium blocker initiation than before. Importantly, the strongest signal for the prescribing cascade was men; patients initiating a specific type of calcium channel blocker called amlodipine; patients starting on a high-dose calcium channel blocker; and patients receiving one or fewer other antihypertensive classes.

In addition, researchers estimated that the incidence of the prescribing cascade was doubled in patients 65 or older. They attributed this high incidence to an increased presentation of swelling among older adults.

“We estimated nearly one in nine patients who developed swelling may have experienced this prescribing cascade. Given time restriction during clinic visits, especially in very medically complex patients, it may be difficult for clinicians to identify all cases of swelling that result from the calcium channel blocker,” Vouri said. “Clinicians need to be aware that in many cases, adverse events of medication may look like symptoms associated with aging. It’s important to make sure a patient’s existing medications are not causing the swelling, prior to starting any new medicines. Pharmacists can play a role in assisting clinicians with patient care in this type of scenario. Starting unnecessary medications can lead to financial burdens and subsequence adverse events for patients without instilling any benefit.”

Vouri added it is important for patients to be empowered and speak up when something doesn’t feel right. “Make sure patients communicate with doctors on any new symptoms that may arise following the initiation of a medication. I have talked to many patients who realized that their symptoms were caused by a drug and a new medicine was started for these symptoms. They often assume that is normal practice, which in most cases, it’s not.”

“The use of too many medications especially in elderly patients suffering from multiple chronic conditions is a well-recognized problem, but we oftentimes struggle to discern which medication is essential and which could be safely removed,” said Almut Winterstein, R.Ph., Ph.D., FISPE, a co-author of the study and a professor and the Dr. Robert and Barbara Crisafi Chair in Pharmaceutical Outcomes and Policy in the UF College of Pharmacy as well as director of the UF Center for Drug Evaluation and Safety. “Dr. Vouri’s work in devising methodological approaches that can flag for clinicians when inappropriate prescribing occur can make a substantial contribution to care for these most vulnerable patients.”

The study “Magnitude of and Characteristics Associated With the Treatment of Calcium Channel Blocker-Induced Lower-Extremity Edema With Loop Diuretics” can be found at: https://ja.ma/364Mxh8. Along with Vouri and Winterstein, the other authors included Xinyi Jiang, M.S.; Todd M. Manini, Ph.D.; Laurence M. Solberg, M.D.; Carl Pepine, M.D.; and Daniel C. Malone, Ph.D.

This story was authored by Xinyi Jiang, M.S., a graduate student in the UF College of Pharmacy.