Effects of chlorthalidone: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Major Research Findings

Chlorthalidone is a thiazide diuretic commonly used for blood pressure control in patients with hypertension. 17 Research suggests that chlorthalidone effectively lowers blood pressure. 17 However, chlorthalidone has been found to negatively impact endothelial function, increase inflammation, and worsen oxidative stress compared to spironolactone. 17 Additionally, chlorthalidone can influence heart structure and function, with notable effects in patients with obstructive sleep apnea (OSA). 3 It has also been linked to increased sympathetic nervous system activity and worsening insulin resistance. 12 Furthermore, chlorthalidone can contribute to elevated uric acid levels. 14 Conversely, spironolactone has demonstrated the potential to mitigate these adverse effects. 12 Research comparing chlorthalidone to hydrochlorothiazide reveals that chlorthalidone offers superior blood pressure-lowering and cardioprotective effects. 7 Studies also indicate that chlorthalidone might be more effective at higher doses. 16 However, chlorthalidone is associated with a higher risk of hypokalemia compared to hydrochlorothiazide. 4

Benefits and Risks

Benefit Summary

Chlorthalidone is an effective blood pressure-lowering agent. It offers potential cardioprotective benefits, potentially reducing the risk of cardiovascular events. Additionally, chlorthalidone might demonstrate increased effectiveness at higher doses compared to hydrochlorothiazide.

Risk Summary

Chlorthalidone can negatively impact endothelial function, leading to increased inflammation and oxidative stress. It can also increase sympathetic nervous system activity, worsen insulin resistance, and contribute to elevated uric acid levels. Furthermore, chlorthalidone carries a higher risk of hypokalemia compared to hydrochlorothiazide.

Comparison Across Studies

Commonalities

Multiple studies consistently demonstrate chlorthalidone's effectiveness in lowering blood pressure. Research also suggests that chlorthalidone has the potential to reduce the risk of cardiovascular events.

Differences

Research highlights that chlorthalidone might negatively impact endothelial function, increase inflammation, and worsen oxidative stress compared to spironolactone. Additionally, chlorthalidone is associated with a higher risk of hypokalemia compared to hydrochlorothiazide.

Consistency and Contradictions in Findings

While various studies demonstrate chlorthalidone's effectiveness in blood pressure reduction, its impact on endothelial function remains a subject of debate. Some studies point to potential negative effects, while others haven't observed these impacts.

Practical Implications and Considerations

Chlorthalidone is a valuable medication for managing hypertension. However, it's crucial to consider the potential risks associated with endothelial dysfunction, inflammation, oxidative stress, and hypokalemia. Consulting a doctor is essential for discussing these risks and making informed decisions about chlorthalidone use.

Limitations of Current Research

Research on chlorthalidone's effects is still developing. More research is needed, particularly large-scale, long-term studies, to comprehensively understand its impact on endothelial function.

Future Research Directions

Future research should focus on further investigating chlorthalidone's effects, especially concerning its impact on endothelial function. Larger, long-term studies are necessary to gain a deeper understanding.

Conclusion

Chlorthalidone is an effective medication for managing hypertension but carries potential risks. It's essential to discuss these risks with your doctor before starting chlorthalidone treatment. More research is needed to further investigate the effects of chlorthalidone, particularly its influence on endothelial function.

Literature analysis of 23 papers
Positive Content
20
Neutral Content
3
Negative Content
0
Article Type
14
3
1
3
23
1.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

Author: VongpatanasinWanpen, GiaconaJohn M, PittmanDanielle, MurilloAshley, KhanGhazi, WangJijia, JohnsonTalon, RenJimin, MoeOrson W, PakCharles C Y

Lower blood pressure
Reduced cardiovascular risk
Diabetes risk
Magnesium depletion
Potassium depletion

Thiazide diuretics (TD) are often prescribed to treat hypertension. However, they can also increase the risk of diabetes. This study aims to investigate the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat during TD therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Effects of chlorthalidone plus amiloride compared with amlodipine on short-term blood pressure variability in individuals with hypertension and obstructive sleep apnea: a randomized controlled trial.

Author: LuccaMarcelo B, JorgeJuliano A, CicheleroFabio T, MartinezDenis, BorgesRogério B, HirakataVania N, FuchsFlavio D, FuchsSandra C

Effective hypertension and OSA treatment
Reduced BP variability
NA

Chlorthalidone in combination with amiloride and amlodipine have comparable effects on short-term blood pressure variability in patients with hypertension and obstructive sleep apnea syndrome (OSA).

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Comparative antiplatelet effects of chlorthalidone and hydrochlorothiazide.

Author: BashirKhalid, BurnsTammy, PirruccelloSamuel J, AuritSarah J, HillemanDaniel E

Hypokalemia

Chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) do not have antiplatelet effects in healthy volunteers.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study.

Author: ArmstrongNicole D, SrinivasasainagendraVinodh, ChekkaLakshmi Manasa S, NguyenNam H K, NahidNoor A, JonesAlana C, TannerRikki M, HidalgoBertha A, LimdiNita A, ClaasSteven A, GongYan, McDonoughCaitrin W, Cooper-DeHoffRhonda M, JohnsonJulie A, TiwariHemant K, ArnettDonna K, IrvinMarguerite R

BP control
Glucose control
Cardiovascular events

This study investigated genetic variants associated with the efficacy of chlorthalidone treatment in African Americans (AAs) with hypertension. Genome-wide association analyses identified variants associated with blood pressure (BP) response and fasting glucose (FG) changes during chlorthalidone treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

6.

Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease: A Randomized, Open-Label Trial.

Author: EdwardsNicola C, PriceAnna M, MehtaSamir, HiemstraThomas F, KaurAmreen, GreasleyPeter J, WebbDavid J, DhaunNeeraj, MacIntyreIain M, FarrahTariq, MelvilleVanessa, HerreyAnna S, SlinnGemma, WaleRebekah, IvesNatalie, WheelerDavid C, WilkinsonIan, SteedsRichard P, FerroCharles J, TownendJonathan N

Arterial stiffness reduction
Early-stage CKD
Left ventricular mass reduction

Spironolactone treatment in early-stage CKD reduced left ventricular mass and arterial stiffness, but it is unclear whether this is due to blood pressure reduction or specific effects of the drug.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Superior antihypertensive and cardioprotective effects of chlorthalidone compared with hydrochlorothiazide.

Author: ChrysantS G, ChrysantG S

Cardioprotection
Superior antihypertensive effectiveness

This review compares hydrochlorothiazide (HCTZ) and chlorthalidone (CTD), two commonly used diuretics for hypertension. While both drugs share common features, CTD has demonstrated superior antihypertensive effectiveness and cardiovascular protection compared to HCTZ.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Race-Specific Comparisons of Antihypertensive and Metabolic Effects of Hydrochlorothiazide and Chlorthalidone.

Author: ChekkaLakshmi Manasa S, ChapmanArlene B, GumsJohn G, Cooper-DeHoffRhonda M, JohnsonJulie A

Treats hypertension

Chlorthalidone and hydrochlorothiazide (HCTZ) were compared as first-line therapies for white and black hypertensive patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial.

Author: HayerManvir K, EdwardsNicola C, SlinnGemma, MoodyWilliam E, SteedsRick P, FerroCharles J, PriceAnna M, AndujarCecilio, DuttonMary, WebsterRachel, WebbDavid J, SempleScott, MacIntyreIain, MelvilleVanessa, WilkinsonIan B, HiemstraThomas F, WheelerDavid C, HerreyAnna, GrantMargaret, MehtaSamir, IvesNatalie, TownendJonathan N

Arterial stiffness reduction
LV mass reduction

Chronic kidney disease (CKD) is a condition in which the kidneys do not work properly. This study looked at whether spironolactone, a drug that is used to treat heart failure, could improve left ventricular mass and arterial stiffness in people with CKD. The study found that spironolactone improved these measures in people with CKD.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

11.

Effects of Food Intake on the Pharmacokinetics of Azilsartan Medoxomil and Chlorthalidone Alone and in Fixed-Dose Combination in Healthy Adults.

Author: DudkowskiCaroline, KarimAziz, MunsakaMelvin

Hypertension treatment

Food intake had a minimal effect on the plasma pharmacokinetics of azilsartan and chlorthalidone when administered as separate tablets or in fixed-dose combination (FDC).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

12.

Negative effects of chlorthalidone on sympathetic nervous system and insulin resistance in hypertensive patients may be avoided with spironolactone: further studies are still needed.

Author: Castro-TorresY, Fleites-PérezA, Carmona-PuertaR, Jiménez-GarridoR G

Controls blood pressure
Insulin resistance
Sympathetic nervous system activity

This abstract discusses the contrasting effects of chlorthalidone and spironolactone on sympathetic nervous system activity and insulin resistance in hypertensive patients. Further investigation is needed to understand these differences and determine the potential benefits of combining these drugs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects.

Author: RoushGeorge C, ErnstMichael E, KostisJohn B, TandonSuraj, SicaDomenic A

Lower blood pressure
Metabolic adverse effects

Indapamide is more potent than hydrochlorothiazide at commonly prescribed doses without evidence for greater adverse metabolic effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

14.

Parallel-group 8-week study on chlorthalidone effects in hypertensives with low kidney function.

Author: CirilloMassimo, MarcarelliFabiana, MeleAlessandra A, RomanoMassimo, LombardiCinzia, BilancioGiancarlo

Improved blood pressure

Chlorthalidone's short-term effects were not reduced in hypertensives with low kidney function. Both groups experienced similar blood pressure reductions and adverse event rates.

Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

Long-term effects of chlorthalidone versus hydrochlorothiazide on electrocardiographic left ventricular hypertrophy in the multiple risk factor intervention trial.

Author: ErnstMichael E, NeatonJames D, GrimmRichard H, CollinsGary, ThomasWilliam, SolimanElsayed Z, PrineasRonald J,

Lower left ventricular hypertrophy

Chlorthalidone, a diuretic, reduced 24-hour blood pressure more effectively than hydrochlorothiazide, potentially leading to a difference in mortality observed in a previous study.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

16.

Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium.

Author: ErnstMichael E, CarterBarry L, ZhengShimin, GrimmRichard H

Reduce cardiovascular events

Low-dose thiazide-based regimens are known to reduce cardiovascular events, but most studies used chlorthalidone, while hydrochlorothiazide (HCTZ) is more widely prescribed. This study compared the dose-response relationships of chlorthalidone and HCTZ for changes in systolic blood pressure and potassium levels.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

17.

Spironolactone and chlorthalidone in uncontrolled elderly hypertensive patients treated with calcium antagonists and angiotensin II receptor-blocker: effects on endothelial function, inflammation, and oxidative stress.

Author: YamanariHiroshi, NakamuraKazufumi, MiuraDaiji, YamanariShuichi, OheTohru

Blood pressure reduction
Endothelial function preservation
Metabolic abnormality
Oxidative stress

Spironolactone may be a more useful add-on therapy than chlorthalidone in hypertensive patients inadequately controlled on candesartan and amlodipine. Spironolactone preserves endothelial function and reduces inflammation compared to chlorthalidone.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

18.

Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients.

Author: MenonDileep V, ArbiqueDebbie, WangZhongyun, Adams-HuetBeverley, AuchusRichard J, VongpatanasinWanpen

Reduced blood pressure
Increased sympathetic activity
Insulin resistance

Chlorthalidone, the first-line drug therapy for hypertension, causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

A Randomised Comparison of the Effects of Nebivolol and Atenolol with and without Chlorthalidone on the Sexual Function of Hypertensive Men.

Author: BoydakBahar, NalbantgilSanem, FiciFrancesco, NalbantgilIstemi, ZoghiMehdi, OzerkanFiliz, TengizIstemihan, ErcanErtuğrul, YilmazHasan, YoketUmit, OnderRemzi

Erectile dysfunction treatment

This study compared the effects of nebivolol and atenolol +/- chlorthalidone on sexual function in hypertensive men. The study found that nebivolol, a beta(1)-selective blocker with nitric oxide-mediated vasodilating activity, had a less negative impact on sexual function compared to atenolol +/- chlorthalidone.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure.

Author: ErnstMichael E, CarterBarry L, GoerdtChris J, SteffensmeierJennifer J G, PhillipsBeth Bryles, ZimmermanM Bridget, BergusGeorge R

Lower blood pressure
Reduced stroke risk

This study compares the effects of chlorthalidone 12.5 mg/day and hydrochlorothiazide 25 mg/day on blood pressure in untreated hypertensive patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Effects of losartan and chlorthalidone on blood pressure and renal vascular resistance index in non-diabetic patients with essential hypertension and normal renal function.

Author: CarusoD, D'AvinoM, AcamporaC, RomanoL, BevilacquaN, CarusoG, EspostiD Degli, BorghiC

Improved renal hemodynamics
Protective renal effect

Losartan, an angiotensin II receptor blocker, is more effective than chlorthalidone, a diuretic, in protecting the kidneys in patients with hypertension. Both drugs were equally effective in lowering blood pressure.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

22.

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.

Author: Serro-AzulJ B, de PaulaR S, GruppiC, PintoL, PierriH, NussbacherA, GebaraO, MoffaP, Pereira-BarretoA C, WajngartenM

Reduces myocardial ischemia

Chlorthalidone reduced myocardial ischemia similarly to diltiazem in elderly hypertensive patients with coronary artery disease. This suggests that reducing arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

23.

[Comparative effects of captopril and chlorthalidone on glucose tolerance and insulin levels essential hypertensives].

Author: ZanellaM T, BaptistaM, CostaC H, KohlmannN E, Kohlmann JúniorO, RibeiroA B

Increased insulin response to glucose
Increased glycemic levels
Reduced insulin sensitivity

Chlortalidone therapy, especially in patients with hypokalemia, may lead to reduced peripheral insulin sensitivity and increased glycemic levels. Captopril therapy, on the other hand, increased insulin response to glucose without affecting insulin sensitivity.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : Portuguese

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