Abstract
Calcium channel blockers, specifically dihydropyridine calcium channel blockers (DH CCBs, eg, amlodipine), may cause lower-extremity edema. Anecdotal reports suggest this may result in a prescribing cascade, where DH CCB-induced edema is treated with loop diuretics. To assess the magnitude and characteristics of the DH CCB prescribing cascade. This cohort study used a prescription sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of DH CCBs among patients aged 20 years or older without heart failure. Data from a private insurance claims database from 2005 to 2017 was analyzed. Use of loop diuretics associated with initiation of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other commonly used medications was used as negative controls. Data were analyzed from March 2019 through October 2019. Initiation of DH CCB or negative control medications. The temporality of loop diuretic initiation relative to DH CCB or negative control initiation. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs were calculated using data from 360 days before and after initiation of DH CCBs. Among 1 206 093 DH CCB initiators, 55 818 patients (4.6%) (33 100 [59.3%] aged <65 years; 32 916 [59.0%] women) had a new loop diuretic prescription 360 days before or after DH CCB initiation, resulting in an aSR of 1.87 (95% CI, 1.84-1.90). An estimated 1.44% of DH CCB initiators experienced the prescribing cascade. The aSR was disproportionately higher among DH CCB initiators who were prescribed high doses (aSR, 2.20; 95% CI, 2.13-2.27), initiated amlodipine (aSR, 1.89; 95% CI, 1.86-1.93), were men (aSR, 1.96; 95% CI, 1.91-2.01), and used fewer antihypertensive classes (aSR, 2.55; 95% CI, 2.47-2.64). The evaluation of ACE inhibitors or ARBs as negative controls suggested hypertension progression may have tempered the incidence of the prescribing cascade (aSR for ACE inhibitors and ARBs, 1.27; 95% CI, 1.24-1.29). This study found an excessive use of loop diuretics following initiation of DH CCBs that cannot be completely explained by secular trends or hypertension progression. The prescribing cascade was more pronounced among those initially prescribed a high dose of DH CCBs.
Highlights
Hypertension is the most common chronic condition in the United States, occurring in nearly half of all adults.[1]
The adjusted sequence ratios (aSRs) was disproportionately higher among Dihydropyridine calcium channel blockers (DH CCBs) initiators who were prescribed high doses, initiated amlodipine, were men, and used fewer antihypertensive classes
The evaluation of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) as negative controls suggested hypertension progression may have tempered the incidence of the prescribing cascade
Summary
Hypertension is the most common chronic condition in the United States, occurring in nearly half of all adults.[1]. A loop diuretic can be used to symptomatically treat DH CCB–induced edema.[14] Use of a loop diuretic for this purpose constitutes a prescribing cascade, in which a drug-induced adverse event prompts additional medication treatment rather than discontinuing or reducing the original prescription.[15] This prescribing cascade can be classified as problematic prescribing[16] because it results in the use of additional medications (eg, potassium supplements) and exacerbates polypharmacy[17] but can lead to preventable adverse events (eg, acute kidney injury, severe dehydration, increased urinary frequency or incontinence, hypotension, fall-related injuries, and electrolyte abnormalities that may result in arrhythmias).[18,19,20,21,22,23,24,25,26,27]
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