Which is better, hydrochlorothiazide or chlorthalidone?
Traditionally, chlorthalidone has been thought to be the "better" drug, though in clinical practice it is often underutilized. In my own clinic, I have certainly found it to be a more potent anti-hypertensive - I have several patients for whom changing this agent finally adequately achieved control. Interestingly, I found this recent paper in JAMA Internal Medicine that compared both of these drugs using retrospective data from three large databases; it found that both are equally effective, but that chlorthalidone has a higher risk of adverse side effects (electrolyte abnormalities, kidney injury, and DM). I have some concerns about this paper: I was surprised at the low number of patients receiving chlorthalidone - only about 5% - and generally when this much explanation (or justification) goes into statistical methodology, I have to wonder about the implications of results. I imagine with cohorts like these it is hard to be sure that the baseline groups are equal, and specifically in this case, that the patients opted into chlorthalidone weren't perhaps already sicker, thereby justifying the use of a more potent drug. My biggest issue, though, is that the timing of labs relative to the initiation of drugs cannot be verified - the authors used a 90-day window - so we have to be very careful about what conclusions we draw. Ultimately I found this article to be thought-provoking but not practice-changing.
Hripcsak G, Suchard MA, Shea S, et al. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Internal Medicine. 2020;180(4):542.
