Association of the Prescribing Cascade Between Calcium Channel Blockers and Loop Diuretics for Middle‐Aged Patients With Hypertension

Background Calcium channel blockers (CCBs) cause peripheral edema. CCB‐induced edema is considered diuretic resistant, but many CCB‐induced edema cases are treated with diuretics in clinical practice. Therefore, to prevent potentially inappropriate medication and mitigate possible polypharmacy, this study aimed to evaluate the incidence of the potential prescribing cascade and compare it with that of other hypertensive agents among middle‐aged patients with hypertension in Japan. Methods We conducted a retrospective cohort study using claims data provided by DeSC Healthcare, Inc. Patients prescribed CCBs or renin–angiotensin system (RAS) agents (angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers) between April 2015 and September 2020 were included. The primary outcome was the prescription of loop diuretics. Multivariable Cox proportional hazards regression models accounting for competing risks were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for loop diuretic use, adjusting for a set of covariates. Results From the extracted data, 45,861 and 33,338 patients were prescribed CCBs and RAS agents, respectively. The proportion of female patients was slightly lower among those prescribed RAS agents than among those prescribed CCBs (41.3% vs. 41.1%). After adjustment, patients prescribed CCBs had a higher risk of loop diuretic prescriptions than those prescribed RAS agents (HR [95% CI]: 1.307 [1.055–1.619]). Conclusions We demonstrated that among middle‐aged patients with hypertension, those newly started on CCBs had a 30% higher rate of being newly prescribed loop diuretics within a 1‐year period than those on RAS inhibitors.