Thiazide Diuretic Utilization Within the VA
Background: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends chlorthalidone as the preferred thiazide diuretic. We aimed to better understand thiazide prescribing patterns within the US Department of Veterans Affairs (VA).
Methods: A retrospective analysis was conducted of patients with a prescription for hydrochlorothiazide (HCTZ), chlorthalidone, indapamide, or any combination products containing these from January 1, 2016, to January 21, 2022. The primary objective was to determine the utilization rates of each thiazide in the active cohort, assessed via χ2 test with Bonferroni correction. Secondary objectives included concomitant potassium or magnesium supplementation, blood pressure rates and control, and thiazide use from January 1, 2016, to December 31, 2021.
Results: Of 628,994 active thiazide prescriptions, utilization rates differed significantly between thiazide groups (P < .001). Rates for HCTZ, chlorthalidone, and indapamide were 84.6%, 14.9%, and 0.5%, respectively. HCTZ use decreased from 90.2% to 83.5% (P < .001) and chlorthalidone use increased from 9.3% to 16.0% (P < .001). Between thiazide groups, rates of blood pressure control were not significantly different (P = .58). Potassium or magnesium supplementation was significantly different between groups (P < .001). The highest concomitant supplementation was with indapamide followed by chlorthalidone and HCTZ with rates of 27.1%, 22.6%, and 12.4%, respectively.
Conclusions: Despite guideline recommendations for chlorthalidone, HCTZ is the most prescribed thiazide diuretic within the VA. However, there was a significant trend toward increased chlorthalidone prescribing from 2016 to 2021. Application of these data may guide further research to increase guideline-recommended therapy.
Limitations
This study was limited by its retrospective design, gaps in data, duplicate active prescription data, and the assessment of concomitant electrolyte supplementation. As with any retrospective study, there is a potential for confounding and a concern for information bias with missing information. This study relied on proper documentation of prescription and demographic information in the Veterans Health Information Systems and Technology Architecture (VistA), as the CDW compiles information from this electronic health record. Strengths of the VistA include ease in clinical functions, documentation, and the ability for records to be updated from any VA facility nationally. However, there is always the possibility of user error and information to be omitted.
In our study, the documentation of BP values and subsequent analysis of overall BP control were limited. For BP values to be included in this study, they had to be recorded after the active thiazide prescription was written and from an in-person encounter documented in VistA. The COVID-19 pandemic shifted the clinical landscape and many primary care appointments during the active cohort evaluation period were conducted virtually. Therefore, patients may not have had formal vitals recorded. There may also be an aspect of selection bias regarding the chlorthalidone group. Although rates of thiazide switching were not assessed, some patients may have been switched from HCTZ or indapamide to chlorthalidone to achieve additional BP control. Thus, patients receiving chlorthalidone may represent a more difficult-to-control hypertensive population, making a finding of similar BP control rates between HCTZ and chlorthalidone an actual positive finding regarding chlorthalidone. Finally, this study did not assess adherence to medications. As the intent of the study was to analyze prescribing patterns, it is impossible to know if the patient was actively taking the medication at the time of assessment. When considering the rates of BP control, there were limited BP values, a potential for selection bias, and neither adherence nor patient self-reported home BP values were assessed. Therefore, the interpretation of overall BP control must be done with caution.
Additionally, duplicate prescriptions were noted in the active cohort. Rates of duplication were 0.2%, 0.08%, and 0.09% for HCTZ, chlorthalidone, and indapamide, respectively. With these small percentages, we felt this would not have a significant impact on the overall thiazide use trends seen in our study. Patients can receive prescriptions from multiple VA facilities and may have > 1 active prescriptions. This has been mitigated in recent years with the introduction of the OneVA program, allowing pharmacists to access any prescription on file from any VA facility and refill if needed (except controlled substance prescriptions). However, there are certain instances in which duplicate prescriptions may be necessary. These include patients enrolled and receiving care at another VA facility (eg, traveling for part of a year) and patients hospitalized at a different facility and given medications on discharge.
With the overall low rate of duplication prescriptions seen in each thiazide group, we determined that this was not large enough to cause substantial variation in the results of this evaluation and was unlikely to alter the results. This study also does not inform on the incidence of switching between thiazide diuretics. If a patient was switched from HCTZ to chlorthalidone in 2017, for example, a prescription for HCTZ and chlorthalidone would have been reported in this study. We felt that the change in chlorthalidone prescribing from January 1, 2016, to December 31, 2021, would reflect overall utilization rates, which may include switching from HCTZ or indapamide to chlorthalidone in addition to new chlorthalidone prescriptions.
Finally, there are confounders and trends in concomitant potassium or magnesium supplementation that were not accounted for in our study. These include concomitant loop diuretics or other medications that may cause electrolyte abnormalities and the dose-dependent relationship between thiazide diuretics and electrolyte abnormalities.10 Actual laboratory values were not included in this analysis and thus we cannot assess whether supplementation or management of electrolyte disturbances was clinically appropriate.
Conclusions
Thiazide utilization patterns have shifted possibly due to the 2017 ACC/AHA BP guideline recommendations. However, HCTZ continues to be the most widely prescribed thiazide diuretic within the VA. There is a need for future projects and clinician education to increase the implementation of guideline-recommended therapy within the VA, particularly regarding chlorthalidone use.
