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Evaluation of a common prescribing cascade of calcium channel blockers and diuretics in older adults with hypertension

Savage RD, Visentin JD, Bronskill SE, Wang X, Gruneir A, Giannakeas V, Guan J, Lam K, Luke MJ, Read SH, Stall NM, Wu W, Zhu L, Rochon PA, McCarthy LM. JAMA Intern Med. 2020; Feb 24 [Epub ahead of print]. DOI: https://doi.org/10.1001/jamainternmed.2019.7087


Importance — Calcium channel blockers (CCBs) are commonly prescribed agents for hypertension that can cause peripheral edema. A prescribing cascade occurs when the edema is misinterpreted as a new medical condition and a diuretic is subsequently prescribed to treat the edema. The extent to which this prescribing cascade occurs at a population level is not well understood.

Objective — To measure the association between being newly dispensed a CCB and subsequent dispensing of a loop diuretic in older adults with hypertension.

Design, Setting, and Participants — A population-based cohort study was performed using linked health administrative databases of community-dwelling adults 66 years or older with hypertension and new prescription drug claims from September 30, 2011, to September 30, 2016, in Ontario, Canada. The dates of analysis were September 1, 2018, to May 30, 2019.

Exposures — Individuals who were newly dispensed a CCB were compared with the following 2 groups: (1) individuals who were newly dispensed an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and (2) individuals who were newly dispensed an unrelated medication.

Main Outcomes and Measures — Hazard ratios (HRs) with 95% CIs were estimated for individuals who were dispensed a loop diuretic within 90 days of follow-up using Cox proportional hazards regression models.

Results — The cohort included 41 086 older adults (≥66 years) with hypertension who were newly dispensed a CCB, 66 494 individuals who were newly dispensed another antihypertensive medication, and 231 439 individuals who were newly dispensed an unrelated medication. At index (ie, the dispensing date), the mean (SD) age was 74.5 (6.9) years, and 191 685 (56.5%) were women. Individuals who were newly dispensed a CCB had a higher cumulative incidence at 90 days of being dispensed a loop diuretic than individuals in both control groups (1.4% vs 0.7% and 0.5%, P < .001). After adjustment, individuals who were newly dispensed a CCB had increased relative rates of being dispensed a loop diuretic compared with individuals who were newly dispensed an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (HR, 1.68; 95% CI, 1.38-2.05 in the first 30 days after index [days 1-30]; 2.26; 95% CI, 1.76-2.92 in the subsequent 30 days [days 31-60]; and 2.40; 95% CI, 1.84-3.13 in the third month of follow-up [days 61-90]) and individuals who were newly dispensed unrelated medications (HR, 2.51; 95% CI, 2.13-2.96 for 1-30 days after index; 2.99; 95% CI, 2.43-3.69 for 31-60 days after index; and 3.89; 95% CI, 3.11-4.87 for 61-90 days after index). This association persisted, although slightly attenuated, from 90 days to up to 1 year of follow-up and when restricted to a subgroup of individuals who were newly dispensed amlodipine.

Conclusions and Relevance — Many older adults with hypertension who are newly dispensed a CCB subsequently receive a loop diuretic. Given how widely CCBs are prescribed, interventions are needed to raise clinicians’ awareness of this common prescribing cascade to reduce the prescribing of potentially unnecessary medications that may cause harm.

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