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Cureus Sep 2023Heart failure (HF) is a notable public health issue, and intravenous loop diuretics are frequently employed to address acute decompensated heart failure (ADHF) and... (Review)
Review
Heart failure (HF) is a notable public health issue, and intravenous loop diuretics are frequently employed to address acute decompensated heart failure (ADHF) and alleviate symptoms of congestion. However, prolonged use of loop diuretics can lead to drug resistance, and some patients experience refractory volume overload that does not respond to treatment. Sequential nephron blockade, which involves combining loop and thiazide diuretics, has been proposed as a strategy to overcome diuretic resistance and improve fluid overload management. This systematic review aims to critically evaluate the effectiveness and safety of this combination diuretic therapy. Following the directives detailed in the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted. Eligibility criteria were established to select relevant studies, including the requirement for studies to be conducted on human subjects and published as free full-text papers in English within the last 10 years. Several databases were searched using a combination of Medical Subject Heading (MeSH) phrases and keywords related to heart failure, loop diuretics, and thiazide diuretics. The search yielded 948 references, and after screening titles, abstracts, and full-text papers, eight final studies (five observational studies and three randomized control trials) were included in the review. Based on the findings of this systematic review, there is substantial evidence to endorse the efficacy of combination diuretic therapy of loop and thiazide diureticsĀ in augmenting diuresis and enhancing outcomes for patients who exhibit insufficient responses to single-agent diuretics. Additionally, the review provides valuable insights about the timing and type of diuretics to use, helping clinicians make informed therapeutic decisions. However, to ensure patient safety and well-being, it is imperative to take into account the potential for electrolyte disturbances and impacts on renal function, necessitating diligent and vigilant monitoring as well as effective management strategies. In light of these findings, further research is warranted to optimize the dosing regimens and to delve deeper into the long-term safety and efficacy of combination therapy. Such research endeavors will undoubtedly contribute to refining treatment approaches and advancing patient care in the field of HF management.
PubMed: 37720125
DOI: 10.7759/cureus.44624 -
European Review For Medical and... Apr 2021Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF.
MATERIALS AND METHODS
We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases.
RESULTS
Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison.
CONCLUSIONS
None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.
Topics: Acute Disease; Carbonic Anhydrase Inhibitors; Diuretics; Drug Resistance; Heart Failure; Humans; Randomized Controlled Trials as Topic
PubMed: 33877660
DOI: 10.26355/eurrev_202104_25550 -
The Cochrane Database of Systematic... May 2014Hypertension is a modifiable cardiovascular risk factor. Although it is established that low-dose thiazides reduce mortality as well as cardiovascular morbidity, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is a modifiable cardiovascular risk factor. Although it is established that low-dose thiazides reduce mortality as well as cardiovascular morbidity, the dose-related effect of thiazides in decreasing blood pressure has not been subject to a rigorous systematic review. It is not known whether individual drugs within the thiazide diuretic class differ in their blood pressure-lowering effects and adverse effects.
OBJECTIVES
To determine the dose-related decrease in systolic and/or diastolic blood pressure due to thiazide diuretics compared with placebo control in the treatment of patients with primary hypertension. Secondary outcomes included the dose-related adverse events leading to patient withdrawal and adverse biochemical effects on serum potassium, uric acid, creatinine, glucose and lipids.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1), Ovid MEDLINE (1946 to February 2014), Ovid EMBASE (1974 to February 2014) and ClinicalTrials.gov.
SELECTION CRITERIA
We included double-blind, randomized controlled trials (RCTs) comparing fixed-dose thiazide diuretic monotherapy with placebo for a duration of 3 to 12 weeks in the treatment of adult patients with primary hypertension.
DATA COLLECTION AND ANALYSIS
Two authors independently screened articles, assessed trial eligibility, extracted data and determined risk of bias. We combined data for continuous variables using a mean difference (MD) and for dichotomous outcomes we calculated the relative risk ratio (RR) with 95% confidence interval (CI).
MAIN RESULTS
We included 60 randomized, double-blind trials that evaluated the dose-related trough blood pressure-lowering efficacy of six different thiazide diuretics in 11,282 participants treated for a mean duration of eight weeks. The mean age of the participants was 55 years and baseline blood pressure was 158/99 mmHg. Adequate blood pressure-lowering efficacy data were available for hydrochlorothiazide, chlorthalidone and indapamide. We judged 54 (90%) included trials to have unclear or high risk of bias, which impacted on our confidence in the results for some of our outcomes.In 33 trials with a baseline blood pressure of 155/100 mmHg, hydrochlorothiazide lowered blood pressure based on dose, with doses of 6.25 mg, 12.5 mg, 25 mg and 50 mg/day lowering blood pressure compared to placebo by 4 mmHg (95% CI 2 to 6, moderate-quality evidence)/2 mmHg (95% CI 1 to 4, moderate-quality evidence), 6 mmHg (95% CI 5 to 7, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence), 8 mmHg (95% CI 7 to 9, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence) and 11 mmHg (95% CI 6 to 15, low-quality evidence)/5 mmHg (95% CI 3 to 7, low-quality evidence), respectively.Direct comparison of doses did not show evidence of dose dependence for blood pressure-lowering for any of the other thiazides for which RCT data were available: bendrofluazide, chlorthalidone, cyclopenthiazide, metolazone or indapamide.In seven trials with a baseline blood pressure of 163/88 mmHg, chlorthalidone at doses of 12.5 mg to 75 mg/day reduced average blood pressure compared to placebo by 12.0 mmHg (95% CI 10 to 14, low-quality evidence)/4 mmHg (95% CI 3 to 5, low-quality evidence).In 10 trials with a baseline blood pressure of 161/98 mmHg, indapamide at doses of 1.0 mg to 5.0 mg/day reduced blood pressure compared to placebo by 9 mmHg (95% CI 7 to 10, low-quality evidence)/4 (95% CI 3 to 5, low-quality evidence).We judged the maximal blood pressure-lowering effect of the different thiazides to be similar. Overall, thiazides reduced average blood pressure compared to placebo by 9 mmHg (95% CI 9 to 10, high-quality evidence)/4 mmHg (95% CI 3 to 4, high-quality evidence).Thiazides as a class have a greater effect on systolic than on diastolic blood pressure, therefore thiazides lower pulse pressure by 4 mmHg to 6 mmHg, an amount that is greater than the 3 mmHg seen with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors, and the 2 mmHg seen with non-selective beta-blockers. This is based on an informal indirect comparison of results observed in other Cochrane reviews on ACE inhibitors, ARBs and renin inhibitors compared with placebo, which used similar inclusion/exclusion criteria to the present review.Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides. These effects were dose-related and were least for hydrochlorothiazide. Chlorthalidone increased serum glucose but the evidence was unclear for other thiazides. There is a high risk of bias in the metabolic data. This review does not provide a good assessment of the adverse effects of these drugs because there was a high risk of bias in the reporting of withdrawals due to adverse effects.
AUTHORS' CONCLUSIONS
This systematic review shows that hydrochlorothiazide has a dose-related blood pressure-lowering effect. The mean blood pressure-lowering effect over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews, which compared these antihypertensive drug classes with placebo and used similar inclusion/exclusion criteria.Thiazides did not increase withdrawals due to adverse effects in these short-term trials but there is a high risk of bias for that outcome. Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Chlorthalidone; Essential Hypertension; Humans; Hydrochlorothiazide; Hypertension; Indapamide; Middle Aged; Randomized Controlled Trials as Topic; Sodium Chloride Symporter Inhibitors
PubMed: 24869750
DOI: 10.1002/14651858.CD003824.pub2