(SLA-160) Magnitude and Patterns of Potential Diuretic Prescribing Cascades after Calcium Channel Blocker Initiation in Medicare Beneficiaries with and without Congestive Heart Failure

Background: Prescribing cascades (PCs) occur when a drug-induced adverse event prompts additional medication. Several studies have documented the risk of diuretic PCs after initiation of dihydropyridine calcium channel blockers (DH-CCBs). However, previous studies have excluded patients with congestive heart failure, assuming diuretics in this population are utilized for fluid overload compared to DH-CCB-induced edema. In practice, distinguishing between CHF-related and DH-CCB-induced edema is challenging, raising concerns that some CHF patients are prescribed diuretics unnecessarily. Determining whether diuretic PCs differ between CHF and non-CHF patients is critical for improving medication safety and preventing polypharmacy.

Objectives: To evaluate diuretic-involved PCs, stratified by CHF status in Medicare beneficiaries newly initiated on DH-CCB using sequence symmetry analysis.

Methods: Using claims data from 5% (2011-15) and 15% (2016-20) samples of Medicare fee-for-service beneficiaries, we identified new DH-CCB users aged ≥66 y with continuous enrollment ≥360 days pre- and ≥180 days post-DH-CCB initiation. Individuals were classified into CHF or non-CHF groups based on the presence of CHF diagnosis ≤360 days prior to DH-CCB initiation. We screened for the initiation of 20 diuretic classes (based on WHO Anatomical Therapeutic Classification level 4) within ±90 days of DH-CCB initiation. In both groups, adjusted SRs (aSRs), representing proportions of DH-CCB initiators starting diuretic class after vs. before DH-CCB, were calculated, with 95% CIs >1 considered significant.

Results: There were 53,596 DH-CCB initiators with CHF and 335,226 without CHF. Among 20 diuretic classes screened, six signals (aSR and 95% CI >1) were significant in the non-CHF group, including aldosterone antagonists (C03DA) (2.12; 95% CI [1.96–2.30]), other potassium-sparing agents (C03DB) (2.04; 95% CI [1.33–3.13]), high-ceiling sulfonamides (C03CA) (2.17; 95% CI [2.09–2.25]), low-ceiling sulfonamides (C03BA) (1.52; 95% CI [1.42–1.62]), low-ceiling diuretics and potassium-sparing agents (C03EA) (1.32 [1.22–1.43]), and thiazides (C03AA) (1.06; 95% CI [1.02–1.09]). However, in the CHF group, only low-ceiling sulfonamides (C03BA) (1.47; 95% CI [1.30–1.65]) was significant.

Conclusions: Potential diuretic PCs were more prevalent in non-CHF patients, likely reflecting a mix of true PCs and therapeutic progression of hypertension treatment. Conversely, CHF patients had less evidence of excess diuretic prescribing after DH-CCB initiation. Further research should investigate whether this reflects appropriate management, alternative edema treatment, or misclassification of DH-CCB-induced edema as CHF-related fluid overload.