By Martin Lipsky, MD

Chancellor, South Jordan Campus, Roseman University of Health Sciences, South Jordan, UT

Dr. Lipsky reports no financial relationships relevant to this field of study.

SYNOPSIS: Many older adults who are prescribed calcium channel blockers subsequently receive a loop diuretic. Awareness of this common cascade may reduce unnecessary prescribing and potential harm.

SOURCE: Savage RD, Visentin JD, Bronskill SE, et al. Evaluation of a common prescribing cascade of calcium channel blockers and diuretics in older adults with hypertension. JAMA Intern Med 2020; Feb 24. doi: 10.1001/jamainternmed.2019.7087. [Epub ahead of print].

Calcium channel blockers (CCBs) often are prescribed as first-line medications for treating hypertension.1 This occurs, in part, because of a perceived low incidence of adverse events and a limited need for routine lab monitoring.2

However, depending on the CCB type, dosage, and duration of therapy, the incidence of peripheral edema ranges from 2% to 25%. Using health administrative databases of community dwelling adults age 66 years and older, Savage et al compared the incidence of subsequent diuretic prescriptions in individuals newly prescribed CCBs to those newly dispensed an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) and individuals newly prescribed an unrelated medication.

The study cohort included 41,046 individuals (older than age 66 years) with hypertension who were newly prescribed a CCB, 66,494 newly prescribed another hypertensive medication, and 231,439 newly prescribed another medication. Individuals prescribed a CCB were more likely to receive a subsequent loop diuretic prescription (1.4%) vs. those prescribed an ACEI (0.7%) or ARB (0.5%). After adjustment, individuals who were newly dispensed a CCB were more likely to receive a loop diuretic vs. individuals who were newly dispensed an ACEI or ARB: hazard ratio (HR), 1.68; 95% confidence interval (CI), 1.38-2.05 in the first 30 days after index (days 1-30); HR, 2.26; 95% CI, 1.76-2.92 in the subsequent 30 days (days 31-60); and HR, 2.40; 95% CI, 1.84-3.13 in the third month of follow-up (days 61-90). For patients who were newly dispensed unrelated medications: HR, 2.51; 95% CI, 2.13-2.96 for days 1-30 after index; HR, 2.99; 95% CI, 2.43-3.69 for days 31-60 after index; and HR, 3.89; 95% CI, 3.11-4.87 for days 61-90 after index.

Considering how widely CCBs are prescribed, the authors noted clinicians should be aware of this common prescribing cascade to reduce the potential of prescribing an unnecessary medication that may cause harm.

COMMENTARY

A key concept when caring for older patients is to use the fewest and lowest doses of medications to achieve a desired result. Each additional medicine synergistically increases the risk of adverse events, highlighting the importance of avoiding the cascading use of medications. This study highlights an example of a cascade effect. Using CCBs increases the likelihood of receiving another prescription for a diuretic by more than 60% when compared to other hypertensive medications.3 Potential risks from reflexively adding a diuretic to a CCB for peripheral edema include increasing the number of falls, triggering incontinence, overdiuresis in euvolemic patients, and more diagnostic testing. While the percentages revealed in this study seem small, prescribing a diuretic to 3.5% of those taking a CCB represents as many as 500,000 to 1.3 million individuals potentially taking an unnecessary medication.

Typically, peripheral edema occurs more frequently in dihydropyridine CCBs compared with non-dihydropyridine CCBs (e.g., verapamil and diltiazem),2 Savage et al did not find this association in their study. One explanation might be related to the prescribing indication (e.g., atrial fibrillation rather than hypertension) or to differences in how the edema was managed.

In an accompanying editorial, Anderson and Steinman noted CCBs are not alone among antihypertensives for causing a pharmacologic cascade.4 Other examples include ACEIs and antitussives, diuretics and bladder antispasmodics for urinary frequency, and antihistamines for dizziness related to antihypertensive treatment. Also, they noted prescribing an antihypertensive may represent a cascade-induced effect from medications such as nonsteroidal anti-inflammatory drugs, which might elevate blood pressure.

CCBs remain an effective antihypertensive therapy, and still should be considered a part of a primary care clinician’s toolbox for treating high blood pressure. However, before prescribing a diuretic to treat CCB-related edema, options should include nonpharmacologic management such as elevation and support stockings, considering if the CCB can be cut off, or whether the patient can be switched to another therapy.

REFERENCES

  1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018;71:e13-e115.
  2. Nerenberg KA, Zarnke KB, Leung AA, et al. Hypertension Canada’s 2018 guidelines for diagnosis, risk assessment, and treatment of hypertension in adults and children. Can J Cardiol 2018;34:505-525.
  3. Makani H, Bangalore S, Romero J, et al. Peripheral edema associated with calcium channel blockers: Incidence and withdrawal rate — a meta-analysis of randomized trials. J Hypertens 2011;29:1270-1280.
  4. Anderson TS, Steinman MA. Antihypertensive prescribing cascades as high priority targets for deprescribing. JAMA Intern Med 2020; Feb 24. doi: 10.1001/jamainternmed.2019.7082. [Epub ahead of print].