Serum chloride and the response to hydrochlorothiazide in patients with acute heart failure: a post-hoc analysis from the CLOROTIC trial.

In 30 seconds

This post-hoc analysis of the multicentre, randomised CLOROTIC trial examined whether baseline serum chloride modified the efficacy or safety of adding oral hydrochlorothiazide to intravenous furosemide in 230 patients with acute heart failure. Hydrochlorothiazide’s effects on several decongestion measures appeared greater in patients with hypo- or normochloremia than in those with hyperchloremia, but only the interaction for weight loss at 72 hours was significant (P = .02). Continuous chloride levels did not significantly modify efficacy, mortality, or rehospitalization effects. Baseline hypochloremia was associated with greater hypokalemia risk among hydrochlorothiazide recipients.

Key findings

• Hypochloremia (< 96 mmol/L) and hyperchloremia (> 106 mmol/L) were present in 17% and 9% of patients, respectively.
• Only weight loss at 72 hours showed a significant interaction between chloride category and hydrochlorothiazide effect (P = .02).
• Modeled continuously, baseline chloride did not significantly interact with hydrochlorothiazide effects on efficacy, mortality, or rehospitalization.
• Among hydrochlorothiazide recipients, baseline hypochloremia was associated with increased hypokalemia risk (potassium< 3.5 mmol/L; P = .029).

Why it matters

Serum chloride may help contextualize diuretic response and electrolyte risk in acute heart failure, but this analysis does not establish it as a reliable modifier of hydrochlorothiazide’s overall decongestive benefit. The hypokalemia association also highlights a potential safety concern in patients with low baseline chloride when thiazide therapy is added.

What to keep in mind

This was a post-hoc analysis of a trial, and the apparent chloride-category differences were not supported by significant interactions when chloride was modeled continuously.