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Hypokalemia During Decongestion With Loop Diuretics and Hydrochlorothiazide, a Post Hoc Analysis of the CLOROTIC
Alicia Conde-Martel1,2, Marta Hernández-Meneses1, José Luís Morales-Rull3
1Internal Medicine Department, Hospital Universitario de Gran Canaria Dr Negrín, Universidad de Las Palmas de Gran Canaria, Spain (A.C.-M., M.H.-M.).
Insights
Adding hydrochlorothiazide (HCTZ) to furosemide for acute heart failure increases hypokalemia risk, particularly with low baseline potassium. This risk does not impact mortality or readmissions.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The CLOROTIC trial investigated adding hydrochlorothiazide (HCTZ) to furosemide in acute heart failure.
- This subanalysis focused on hypokalemia incidence, risk factors, and outcomes.
Purpose of the Study:
- To evaluate hypokalemia risk with HCTZ addition to furosemide.
- To identify risk factors for hypokalemia.
- To assess hypokalemia's impact on mortality and readmissions.
Main Methods:
- Post hoc analysis of the CLOROTIC trial (230 patients).
- Patients received HCTZ or placebo with intravenous furosemide.
- Hypokalemia (K+ <3.5 mmol/L), mortality, and readmissions were analyzed; Monte Carlo simulation predicted hypokalemia risk.
Main Results:
- Hypokalemia incidence was higher with HCTZ vs. placebo at multiple time points (P<0.001).
- Independent risk factors for hypokalemia included lower baseline potassium, HCTZ treatment, and lack of mineralocorticoid receptor antagonist use.
- No association found between hypokalemia and 30/90-day mortality or readmissions.
Conclusions:
- Adding HCTZ to furosemide increases hypokalemia risk, especially with baseline K+ ≤4.3 mmol/L and without mineralocorticoid receptor antagonists.
- Supplementation with potassium and mineralocorticoid receptor antagonists is recommended when using HCTZ with furosemide.
Background:
In patients with acute heart failure, the addition of hydrochlorothiazide (HCTZ) to furosemide increased the diuretic response in the CLOROTIC trial (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure). The aim of this subanalysis was to evaluate the incidence and risk factors for hypokalemia, and its impact on mortality and readmissions.
Methods:
This is a post hoc analysis of the CLOROTIC trial that randomized 230 patients with acute heart failure and volume overload to receive HCTZ or placebo in addition to intravenous furosemide. The incidence and risk factors for the development of hypokalemia (K+ <3.5 mmol/L) and its association with 30- and 90-day mortality and readmissions were analyzed. The Monte Carlo simulation method was applied to predict the development of hypokalemia.
Results:
The incidence of hypokalemia was significantly higher in the HCTZ group (compared with the placebo group) at 48 and 96 hours after randomization, and at discharge (P<0.001). In a multivariate analysis, the following variables were independently associated with the development of hypokalemia: baseline K+ values (OR per 0.1 units, 0.82 [95% CI, 0.76-0.87]; P<0.001), treatment with HCTZ (OR, 4.90 [95% CI, 2.50-9.90]; P<0.001), and treatment with a mineralocorticoid receptor antagonist at baseline (OR, 0.42 [95% CI, 0.20-0.84]; P=0.017). There was no association between the development of hypokalemia and 30- and 90-day mortality and readmissions. The Monte Carlo simulation method predicted in patients treated with furosemide alone a higher risk of hypokalemia when baseline K+ values are ≤3.7 mmol/L. When HCTZ is added to furosemide, the risk of hypokalemia is present with higher baseline K+ values (≤4.3 mmol/L).
Conclusions:
Adding HCTZ to intravenous furosemide increases the risk of hypokalemia a especially when baseline K+ is ≤4.3 mmol/L and when patients are not treated with a mineralocorticoid receptor antagonist. In patients treated with furosemide and HCTZ, it is advisable to add potassium supplements or a mineralocorticoid receptor antagonist.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01647932.
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