Title: Prescription Trends of Hydrochlorothiazide vs. Chlorthalidone in the United States (2019-2024).

Abstract

Background: Hydrochlorothiazide and chlorthalidone have been cornerstones of hypertension management for decades. Given the historical debate about their comparative effectiveness and cardiovascular outcomes, as well as recent clinical trial evidence, we studied prescription trends to assess the association of prescribing patterns with evolving knowledge.

Methods: We analyzed prescriptions of hydrochlorothiazide and chlorthalidone from January 2019 to December 2024 using IQVIA's National Prescription Audit (NPA). Interrupted Time Series (ITS) analysis assessed inflections in prescribing practice around the December 2022 Diuretic Comparison Project (DCP) findings and the August 2020 hydrochlorothiazide US Food and Drug Administration (FDA) non-melanoma skin cancer warning.

Results: On average, 3,734,790 hydrochlorothiazide and 543,402 chlorthalidone prescriptions were dispensed, a 7:1 ratio. A drop of 503,367 hydrochlorothiazide prescriptions (14%; 95% CI: -673,109 to -333,624) was observed in the first month after the FDA's warning, and the pre-warning 43,913 (95% CI: 31,701 to 56,125) monthly increase reversed to a monthly decline of 13,546 (95% CI: -16,137 to -10,954) prescriptions post-warning. After the DCP report, a slowdown of 2,738 (95% CI: -4,472 to -1,004) monthly prescriptions for chlorthalidone was seen, reducing the rate of monthly increase from 3,602 (95% CI: 1916 to 5289) to 864 (95% CI: 431 to 1298). Monthly hydrochlorothiazide prescriptions declined to -20,124 (95% CI: -26285 to -13962) post DCP report.

Conclusion: The FDA warning and DCP report were associated with a decline in hydrochlorothiazide and chlorthalidone prescriptions, while the DCP report slowed chlorthalidone prescribing.