Serum chloride and the response to hydrochlorothiazide in patients with acute heart failure: a post-hoc analysis from the CLOROTIC trial
P Llacer, D Garcia Escriva, J Perez Silvestre, J Casado, J L Morales Rull, M Sanchez Marteles, A Conde Martel, P Salamanca Bautista, M A Plasin, J M Cerqueiro, P Gil, L Manzano, F Formiga, J C TrullasAbstract
Background
Hypochloremia plays an important role in the pathophysiology of heart failure (HF) as it is associated with worse prognosis and diuretic resistance. This study investigates whether serum chloride is associated with efficacy and safety of hydrochlorothiazide in patients with acute heart failure (AHF).
Methods
This post-hoc analysis included all 230 patients from the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial, randomized to oral hydrochlorothiazide or placebo in addition to intravenous furosemide. The impact of baseline serum chloride on treatment effect of hydrochlorothiazide on the main trial endpoints was assessed.
Results
At baseline, hypochloremia (<96mmol/L) and hyperchloraemia (>106mmol/L) were observed in 39 (17%) and 20 (9%) patients, respectively. Hypochloremia was not associated with decongestion, as measured by weight loss at 72 hours. The effect of hydrochlorothiazide was more pronounced in patients with hypo- or normochloraemia than in those with hyperchloraemia across several efficacy endpoints (weight loss at 72/96 hours, 24-hour diuresis, and diuresis per milligram of furosemide); only weight loss at 72 hours showed a significant differential effect (p=0.02). No significant interaction between serum chloride and the effect of hydrochlorothiazide on mortality or rehospitalization was found. Regarding safety endpoints, baseline hypochloremia was significantly associated with an increased risk of hypokalemia (potassium < 3.5mmol/L) in those allocated to hydrochlorothiazide (p=0.029). There was no evidence of differential effect of hydrochlorothiazide for other safety outcomes across chloraemia status.
Conclusion
In patients with AHF, the addition of hydrochlorothiazide to loop diuretics enhanced the diuretic response irrespective of baseline serum chloride.Restricted cubic spline; weight-chlorideFor image description, please refer to the figure legend and surrounding text.Restrictedcubic spline;diuresis-chlorideFor image description, please refer to the figure legend and surrounding text.