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- Title
Magnitude of and Characteristics Associated With the Treatment of Calcium Channel Blocker–Induced Lower-Extremity Edema With Loop Diuretics.
- Authors
Vouri, Scott Martin; Jiang, Xinyi; Manini, Todd M.; Solberg, Laurence M.; Pepine, Carl; Malone, Daniel C.; Winterstein, Almut G.
- Abstract
Key Points: Question: What is the risk of experiencing the prescribing cascade of treating dihydropyridine calcium channel blocker–induced lower-extremity edema with a loop diuretic? Findings: In this cohort study of 1.2 million patients who initiated a dihydropyridine calcium channel blocker, excessive use of loop diuretics was found, which cannot be fully explained by secular trends or hypertension progression. This was particularly pronounced among patients who received a high dose of dihydropyridine calcium channel blockers. Meaning: In this study, many patients received loop diuretics instead of a dose reduction or discontinuation of dihydropyridine calcium channel blockers, constituting a prescribing cascade. Future studies are needed to test strategies to mitigate or prevent prescribing cascades. This cohort study used prescription sequence symmetry analysis to assess the magnitude and characteristics of the prescribing cascade of treating dihydropyridine calcium channel blocker–induced lower-extremity edema with loop diuretics. Importance: 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. Objective: To assess the magnitude and characteristics of the DH CCB prescribing cascade. Design, Setting, and Participants: 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. Exposures: Initiation of DH CCB or negative control medications. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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.
- Subjects
CALCIUM antagonists; AMLODIPINE; ACE inhibitors; CONFIDENCE intervals; DIURETICS; EDEMA; LEG; STATISTICS; DATA analysis; STATISTICAL significance; POLYPHARMACY; DATA analysis software; DESCRIPTIVE statistics; INAPPROPRIATE prescribing (Medicine)
- Publication
JAMA Network Open, 2019, Vol 2, Issue 12, pe1918425
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2019.18425