Disclosures: Anderson, McCarthy, Savage and Steinman report no relevant financial disclosures.
February 24, 2020
3 min read

Potentially harmful ‘prescribing cascade’ common in older adults with hypertension

Disclosures: Anderson, McCarthy, Savage and Steinman report no relevant financial disclosures.
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Photo of Lisa McCarthy 
Lisa McCarthy
Photo of Rachel Savage 
Rachel D. Savage

Calcium channel blockers that are often prescribed to older adults with hypertension can cause peripheral edema, which many physicians misinterpret as a new medical condition and subsequently prescribe diuretics, according to research published in JAMA Internal Medicine.

“The risks and benefits of treating calcium channel blocker-related edema with diuretics need to be carefully considered by prescribers because diuretics can lead to downstream consequences, some of which are quite serious, like falls,” Lisa McCarthy, PharmD, MSc, a scientist at the Women’s College Research Institute and pharmacist at Women’s College Hospital, Toronto, Canada, told Healio Primary Care.

“Before prescribing a diuretic to manage calcium channel blocker-related edema, we would encourage clinicians to consider whether the calcium channel blocker is still necessary, whether it could be discontinued or the dose reduced, or whether the patient can be switched to another therapy,” she continued.

Adding diuretics to calcium channel blockers (CCBs) for patients experiencing CCB-related edema can increase their risk for overdiuresis and can lead to falls, urinary incontinence, acute kidney injuries and many other downstream consequences, according to researchers.

Reference: Savage RD, et al. JAMA Intern Med. 2020;doi:10.1001/jamainternmed.2019.7087.

McCarthy and colleagues used multiple health administrative databases in Ontario, Canada to conduct a population-based, retrospective cohort study examining diuretic use in adults aged 66 years and older who were newly prescribed CCBs.

Researchers compared the prevalence of diuretic dispensing in 41,086 adults newly prescribed CCBs with 66,494 adults who were newly dispensed other antihypertensive medications and 231,439 adults who were newly dispensed an unrelated medication.

McCarthy and colleagues found that older adults with hypertension who were newly dispensed CCBs had a higher cumulative incidence of being dispensed a loop diuretic at 90 days (1.4%) than those who received other antihypertensive medications (0.7%) or an unrelated medication (0.5%).

Results further showed that those newly dispensed CCBs had increased relative rates of being dispensed a loop diuretic compared with those given other hypertension medications within 30 days (HR = 1.68; 95% CI, 1 .38-2.05), from 31 days to 60 days (HR = 2.26; 95% CI, 1.76-2.92) and from 61 days to 90 days (HR = 2.4; 95% CI, 1.84-3.13).

Relative rates of being dispensed a loop diuretic were also higher among adults receiving CCBs compared with those prescribed unrelated medications at 30 days (HR = 2.51; 95% CI, 2.13-2.96), from 31 days to 60 days (HR = 2.99; 95% CI, 2.43-3.69) and from 61 days to 90 days (HR = 3.89; 95% CI, 3.11-4.87).


At 1 year, researchers determined that 3.5% of older adults given CCBs were dispensed a loop diuretic, compared with 1.8% of adults given other types of antihypertension medications and 1.4% of those given an unrelated medication.

When including the use of any diuretic at 1 year, researchers found that the prevalence rose to 9.5% in those taking CCBs, 7.3% in those taking other antihypertensive medications and 3% in those taking unrelated medications.

“Our findings are important because this prescribing cascade is quite widespread, placing many older adults at risk,” Rachel D. Savage, PhD, postdoctoral fellow at the Women’s College Research Institute at the Women’s College Hospital, Toronto, Canada, told Healio Primary Care. “In 2016, more than 14 million Americans received a prescription for amlodipine — the most commonly prescribed CCB.”

Therefore, the finding that 3.5% of those prescribed CCBs were then given a loop diuretic after 1 year “means approximately 500,000 to 1.3 million new potentially unnecessary diuretic prescriptions each year,” she said.

In a commentary published alongside the study, Timothy S. Anderson, MD, MAS, an instructor in medicine at Beth Israel Deaconess Medical Center and Michael A. Steinman, MD, professor of medicine in the school of medicine at the University of California, San Francisco, explained that the prescribing cascade described in the study could lead to adverse drug events, avoidable diagnostic testing and hospitalizations.

“Identifying prescribing cascades and their consequences is an important step to stem the tide of polypharmacy and inform deprescribing effort,” they wrote. “Ultimately curtailing polypharmacy will require clinicians to routinely assess for adverse drug events following all medication initiations so that when adverse drug events do occur, we can minimize their morbidity and avoid further contributing to prescribing cascades.” – by Erin Michael

Disclosures: Anderson, McCarthy, Savage and Steinman report no relevant financial disclosures.