Comparative antiplatelet effects of chlorthalidone and hydrochlorothiazide

Khalid Bashir, Tammy Burns, Samuel J. Pirruccello, Sarah J. Aurit, Daniel E. Hilleman

Research output: Contribution to journalArticlepeer-review


Chlorthalidone (CTD) may be superior to hydrochlorothiazide (HCTZ) in the reduction of adverse cardiovascular events in hypertensive patients. The mechanism of the potential benefit of CTD could be related to antiplatelet effects. The objective of this study was to determine if CTD or HCTZ have antiplatelet effects. This study was a prospective, double-blind, randomized, three-way crossover comparison evaluating the antiplatelet effects of CTD, HCTZ, and aspirin (ASA) in healthy volunteers. The effects of these treatments on platelet activation and aggregation were assessed using a well-established method with five standard platelet agonists. Thirty-four patients completed the three-way crossover comparing pre- and post-treatment changes in platelet activation and aggregation studies. There were statistically significant antiplatelet effects with ASA but not with CTD or HCTZ. Hypokalemia occurred in 0 (0%), 10 (30%), and 6 (18%) of the ASA, CTD, and HCTZ patients, respectively. The results of our study suggest that the benefits of CTD and HCTZ in reducing adverse cardiovascular events in patients with hypertension is not a result of an antiplatelet effect. In our study, hypokalemia with CTD was more prevalent than that reported in a large outcome trial in patients with hypertension. The clinical relevance of this finding is uncertain.

Original languageEnglish (US)
Pages (from-to)1310-1315
Number of pages6
JournalJournal of Clinical Hypertension
Issue number10
StatePublished - Oct 2022


  • antihypertensive therapy
  • clinical pharmacology
  • hypertension-general
  • pharmacologic (drug) therapy
  • potassium/hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Comparative antiplatelet effects of chlorthalidone and hydrochlorothiazide'. Together they form a unique fingerprint.

Cite this