HCTZ vs. Other Diuretics: Which Works Best for Hypertension?

February 28, 2025/Andrew Le

Diuretics are the oldest class of blood pressure medications, and were the first to demonstrate both effectiveness and safety in the management of blood pressure. They work by removing excess sodium (salt) and water from your body through urine. This process reduces the amount of fluid in your blood vessels, easing pressure on your heart.

Hydrochlorothiazide (HCTZ) is one of the most commonly prescribed diuretics. In 2022 alone, it was prescribed around 38 million times in the US. Since its approval in the 1960s, many other diuretics have been introduced for hypertension. But how do you know if HCTZ is the best option for you?

This article explores HCTZ vs. other diuretics, examining their effectiveness, side effects, and best use cases for managing high blood pressure.

🔑 Key Takeaways

➤ Chlorthalidone and indapamide are more effective than HCTZ in lowering blood pressure. However, they differ in side effect profiles and additional health benefits.

➤ Among thiazide diuretics, chlorthalidone may be more beneficial for those with a history of heart attack or stroke, while indapamide has been shown to improve heart function, particularly in individuals with hypertension and diabetes.

➤ Loop diuretics are primarily used for managing fluid retention rather than controlling high blood pressure.

➤ Potassium-sparing diuretics help prevent potassium loss when combined with HCTZ.

➤ Many patients benefit from a combination of HCTZ with either potassium-sparing diuretics or other antihypertensive medications.

➤ While thiazide diuretics remain a standard treatment for hypertension, their effectiveness and safety vary based on individual patient factors. Personalized treatment selection ensures the best outcomes with minimal side effects.

Hydrochlorothiazide and Other Thiazide Diuretics

Medical guidelines, including those from the American College of Cardiology (ACC) and the American Heart Association (AHA), recommend them as first-line treatment options, especially for mild to moderate high blood pressure.

The most frequently prescribed thiazide diuretics, other than hydrochlorothiazide (HCTZ), are chlorthalidone and indapamide.

Below is a comparison of hydrochlorothiazide and other thiazide diuretics.

ParameterHCTZChlorthalidoneIndapamide
Common BrandsEsidrix, HydrodiurilThalitoneLozol
Dosage Forms and StrengthsTablet or capsule (12.5 mg, 25 mg, 50 mg)Tablet (15 mg, 25 mg, 50 mg)Tablet (1.25 mg, 2.5 mg, 5 mg)
Dosing FrequencyOnce dailyOnce dailyOnce daily
Duration of Action6-12 hours24 hours24 hours (regular version) and up to 32 hours (extended-release version)
Risk of HypokalemiaModerateHigher riskSimilar to HCTZ

Which Lowers Blood Pressure the Most?

Studies show that chlorthalidone and indapamide lower blood pressure more effectively than HCTZ.

A 2023 meta-analysis comparing chlorthalidone and HCTZ found that, on average, chlorthalidone reduced systolic blood pressure (SBP) by 4.84 mmHg and diastolic blood pressure (DBP) by 2.12 mmHg more than HCTZ. Other studies indicate that switching from HCTZ to chlorthalidone may lower SBP by an additional 7-8 mmHg.

There are fewer studies directly comparing indapamide and HCTZ. However, in a study that evaluated all three medications, indapamide lowered SBP by 5.1 mmHg more than HCTZ.

Which Causes More Potassium Loss?

Low potassium levels in the blood, or hypokalemia, is the most common side effect of thiazide diuretics. It can be life-threatening and should be monitored during the first 2-3 weeks of treatment.

Research shows that chlorthalidone lowers potassium more than HCTZ. In one study, 8.9% of chlorthalidone users developed hypokalemia compared to 6.9% of HCTZ users.

Indapamide affects potassium levels similarly to HCTZ. One study found that indapamide 2.5 mg reduced potassium by 0.30 to 0.42 mEq/L, similar to HCTZ 25 mg.

Which is Better for Heart Health?

High blood pressure can gradually damage the heart, making cardiovascular effects an important consideration when choosing antihypertensive medications.

For preventing serious heart conditions like heart failure and stroke, a large analysis of over 730,000 people in the US found that chlorthalidone and HCTZ were equally effective. Similar findings were observed in an evaluation focused on older adults.

However, if you have already had a heart attack or stroke, recent research suggests that chlorthalidone may be the better option for managing blood pressure.

When comparing indapamide to HCTZ, earlier trials revealed that indapamide reduced heart muscle thickening (a risk factor for heart disease) by 17%, whereas HCTZ had little to no effect.

Another investigation assessed how indapamide and HCTZ influenced heart and blood vessel function when combined with an ACE inhibitor (quinapril) in patients with hypertension and type 2 diabetes. With indapamide, results showed:

  • Heart contraction strength increased by 7%
  • Heart muscle flexibility improved by 14%
  • Heart relaxation between beats improved by 31%

These benefits were associated with better blood vessel function. In contrast, no significant improvements in heart function were observed with HCTZ.

Which Provides Better Support for Kidney Health?

Hypertension is a known risk factor for the development and progression of chronic kidney disease (CKD).

A recent analysis conducted at Veterans Affairs (VA) facilities between 2016 and 2023 found no significant difference between chlorthalidone and HCTZ in protecting kidney function. The researchers concluded that either medication can be prescribed for hypertension without concerns about kidney-related risks.

However, comparing HCTZ to indapamide produced different results.

A two-year study reported that indapamide improved kidney function by increasing creatinine clearance (a measure of how well the kidneys filter waste) by 28.5%. Meanwhile, HCTZ had the opposite effect, reducing creatinine clearance by 17.4%.

📄 Summary of HCTZ vs. Other Thiazide Diuretics

Based on the findings above:

➤ Blood Pressure Control: Chlorthalidone and indapamide lower blood pressure more effectively than HCTZ.

➤ Potassium Levels: Chlorthalidone causes more potassium loss than HCTZ, while indapamide affects potassium levels at a similar rate to HCTZ.

➤ Heart Health: Chlorthalidone may be better for those with a history of heart attack or stroke, while indapamide improves heart function more than HCTZ.

➤ Kidney Health: Chlorthalidone and HCTZ have similar effects, but indapamide may offer better kidney protection.

Hydrochlorothiazide and Loop Diuretics

Loop diuretics are stronger than HCTZ and other thiazide diuretics at removing excess fluid because they block sodium reabsorption in a part of the kidney that handles about 25% of sodium reabsorption. In contrast, thiazide diuretics act in a later part of the kidney, where only 5-7% of sodium is reabsorbed.

That’s why they are known as “high-ceiling” and “high-efficiency” diuretics.

However, loop diuretics are not the first choice for treating hypertension. Instead, they are mostly used to treat fluid buildup (edema) caused by heart failure, liver disease, or kidney problems.

When used for hypertension, here’s how they compare to HCTZ:

ParameterHCTZFurosemideTorsemideBumetanide
Common BrandsEsidrix, HydrodiurilLasixDemadexBumex
Dosage Forms and StrengthsTablet or capsule (12.5 mg, 25 mg, 50 mg)Tablet (20 mg, 40 mg, 80 mg)Tablet (5 mg, 10 mg)Tablet (0.5 mg, 1 mg, 2 mg)
Dosing FrequencyOnce dailyTwice dailyOnce dailyOnce or twice daily
Duration of Action6-12 hours6-8 hours6-12 hours3-4 hours
Risk of HypokalemiaModerateLower riskLower riskSimilar to HCTZ (in animal studies)

Which Lowers Blood Pressure the Most?

Most of the available comparisons between HCTZ and loop diuretics for lowering blood pressure are older investigations, with most focusing on furosemide.

One trial found that HCTZ was more effective than furosemide in Black patients with mild to moderate hypertension. Mean arterial pressure (MAP) dropped by 24.7 mmHg with HCTZ compared to 16.0 mmHg with furosemide. Similarly, diastolic blood pressure (DBP) decreased by 17.3 mmHg with HCTZ versus 10.1 mmHg with furosemide.

Other findings have shown similar results, suggesting that HCTZ’s longer duration of action helps maintain consistent fluid reduction throughout the day.

Meanwhile, torsemide appears to be equally effective to HCTZ 25 mg for hypertension when used at low (subdiuretic) doses.

⚡ Quick Insight

Mean arterial pressure (MAP) is the average pressure in the arteries during a full heartbeat cycle, including both contraction (systole) and relaxation (diastole). It is calculated as one-third of your systolic blood pressure plus two-thirds of your diastolic blood pressure.

For patients with normal blood pressure, maintaining a MAP between 65 and 95 mmHg is essential to ensure proper blood flow to vital organs, such as the heart, brain, and kidneys.

MAP is important in hypertension research because it provides a more comprehensive view of blood circulation than SBP or DBP alone. In fact, a recent study found that MAP was the most accurate (95.2%) in detecting the effects of hypertension on brain blood vessels, compared to SBP (89.3%) and DBP (88.9%).

Which Causes More Potassium Loss?

According to the studies above, HCTZ lowers potassium levels more than furosemide, with a 0.26 mEq/L decrease.

Similarly, torsemide causes less potassium loss than HCTZ. In addition, long-term use of torsemide does not lead to other common side effects of HCTZ, such as:

  • Low magnesium
  • Increased blood sugar
  • Altered cholesterol levels
  • High uric acid, which can contribute to gout

An animal study comparing bumetanide and HCTZ found that both increased potassium loss, but the difference was small (106 vs. 99 μEq/min). However, bumetanide did not stop potassium excretion, even when extra potassium was given.

Which is Better for Heart Health?

HCTZ offers better heart protection than loop diuretics.

A 2021 study investigated whether HCTZ could prevent heart damage, specifically heart muscle thickening and scarring, which can lead to heart failure. Using hypertensive rats, researchers found that:

  • Heart muscle thickening and scarring were significantly reduced with HCTZ.
  • ROCK enzyme activity, which promotes heart thickening, stiffness, and scarring, was 54% higher in hypertensive rats but returned to normal levels with HCTZ.
  • Proteins that make the heart stiff and less flexible were reduced with HCTZ.
  • HCTZ suppressed harmful genes linked to heart damage and oxidative stress.

Loop diuretics help manage heart failure by reducing fluid buildup but are not a preventative treatment and may have downsides if misused.

Five-year mortality rates showed that using loop diuretics without a heart failure diagnosis was associated with a higher risk of death (40%) than having heart failure without diuretic use (22%). This suggests that heart failure may be frequently underdiagnosed, that using a loop diuretic signals severe illness, or that inappropriate prescribing worsens patient outcomes–or all three.

Which Provides Better Support for Kidney Health?

Neither HCTZ nor loop diuretics support or enhance kidney function. In fact, both can reduce creatinine clearance, which signals impaired kidney function since it reflects a decline in the kidneys’ ability to filter waste from the blood.

However, when managing hypertension in patients with kidney disease, loop diuretics are generally preferred. According to clinical guidelines, they remain effective even when kidney function is significantly impaired (eGFR <30 mL/min), whereas HCTZ tends to lose effectiveness in such cases. However, this is still debated.

A pilot study compared furosemide and HCTZ in patients with severe CKD (Stage 4 or 5). Both drugs lowered blood pressure, proving that HCTZ still works in advanced CKD, despite previous doubts.

Another review found that both drugs lower blood pressure equally well. Moreover, HCTZ was better than furosemide at increasing sodium and chloride excretion in severe CKD.

📄 Summary of HCTZ vs. Loop Diuretics

Based on the findings above:

➤ Blood Pressure Control: HCTZ lowers blood pressure more effectively than furosemide, while low-dose torsemide is equally effective as HCTZ 25 mg. Loop diuretics are not the first-line treatment for hypertension.

➤ Potassium Levels: HCTZ often leads to greater potassium loss than loop diuretics like furosemide or torsemide.

➤ Heart Health: HCTZ offers better heart protection by reducing heart muscle thickening and scarring.

➤ Kidney Health: Both HCTZ and loop diuretics can impair kidney function.

Hydrochlorothiazide and Potassium-Sparing Diuretics

As the name suggests, potassium-sparing diuretics help retain potassium in the body, preventing low potassium levels (hypokalemia). They also help retain magnesium, which is why they are sometimes called magnesium-sparing diuretics. However, they block only about 3% of the sodium filtered by the kidneys.

These drugs are not typically used as first-line treatment. Instead, they are mainly prescribed to prevent hypokalemia and low magnesium levels (hypomagnesemia) caused by other diuretics.

Below are the commonly prescribed potassium-sparing diuretics for hypertension and how they compare to HCTZ:

ParameterHCTZAmilorideEplerenoneSpironolactoneTriamterene
Common BrandsEsidrix, HydrodiurilMidamor, Hydro-rideInspraAldactoneDyrenium
Dosage Forms and StrengthsTablet or capsule (12.5 mg, 25 mg, 50 mg)Tablet (5mg)Tablet (25 mg, 50 mg)Tablet (25 mg, 50 mg, 100 mg)Capsule (50 mg, 100 mg)
Dosing FrequencyOnce dailyOnce dailyOnce to twice dailyOnce dailyOnce to twice daily
Duration of Action6-12 hours24 hours24 hours24 hours12-16 hours
Risk of HypokalemiaModerateLowLowLowLow

Which Lowers Blood Pressure the Most?

HCTZ reduces blood pressure more than potassium-sparing diuretics alone.

Potassium-sparing diuretics are rarely used alone for hypertension. Instead, they are often combined with other diuretics, such as HCTZ. In fact, these combinations have been available as single medications for years. Research shows they improve effectiveness while reducing the risk of hypokalemia.

One study found that combining amiloride with HCTZ significantly lowered systolic blood pressure (SBP). After 12 weeks, the average blood pressure changes were:

  • Amiloride alone: 153/101 → 139/93 mm Hg
  • Amiloride + HCTZ: 160/100 → 137/90 mm Hg
  • HCTZ alone: 154/101 → 134/89 mm Hg

Similar results were observed when HCTZ was combined with triamterene. One trial reported an average SBP reduction of 3.8 mmHg, while another found a decrease of 4.5 mmHg, both compared to HCTZ alone.

Eplerenone and spironolactone are commonly used for resistant hypertension, which is when blood pressure remains high despite taking three antihypertensive medications. In such cases, they are the go-to add-on therapy to help achieve better blood pressure control.

Which Causes More Potassium Loss?

HCTZ monotherapy causes more potassium loss. To demonstrate, results from a study referenced earlier found:

  • HCTZ alone: -0.59 mEq/L
  • Amiloride + HCTZ: -0.38 mEq/L
  • Amiloride alone: +0.23 mEq/L (potassium increased)

Although potassium-sparing diuretics help reduce potassium loss, monitoring is still essential. Higher doses of these diuretics can lead to hyperkalemia (high potassium levels), which may cause:

  • Weakness or fatigue
  • Irregular heartbeat
  • Tingling or numbness
  • Difficulty breathing

People with kidney disease are at higher risk of hyperkalemia because their kidneys may struggle to remove excess potassium.

Which is Better for Heart Health?

Eplerenone and spironolactone may provide extra heart benefits, particularly in those with uncontrolled hypertension. However, HCTZ also offers strong cardiovascular protection, especially when combined with amiloride or triamterene.

A study found that eplerenone helped blood flow to the heart better than HCTZ. Since both groups had similar blood pressure levels, researchers suggest that this benefit was likely due to eplerenone’s effect on heart health rather than its ability to lower blood pressure.

Other findings show that spironolactone works better than HCTZ in improving blood vessel flexibility in people with uncontrolled high blood pressure. Stiff blood vessels make the heart work harder, increasing the risk of heart problems.

For older adults with hypertension, research found that treatment with HCTZ and amiloride resulted in:

  • 31% lower risk of stroke
  • 44% fewer heart-related problems
  • 35% fewer overall heart and circulation issues

Additionally, combining HCTZ with triamterene (along with methyldopa when needed) led to:

  • 27% fewer deaths from heart-related causes
  • 60% fewer fatal heart attacks
  • 60% fewer severe heart problems
  • 52% fewer non-fatal strokes

Which Provides Better Support for Kidney Health?

When used alone, each diuretic poses kidney-related risks. HCTZ can cause hypokalemia, while potassium-sparing diuretics can cause hyperkalemia. Both conditions can be harmful to kidney health. However, combining amiloride with HCTZ may offer benefits.

A study found that amiloride with HCTZ increased the production of prostaglandin E2 (PGE2) in the kidneys. PGE2 helps maintain steady blood flow to the kidneys and supports their ability to filter waste. In contrast, triamterene with HCTZ reduced PGE2 production. This suggests that it may not support kidney function as well as amiloride does.

Another study showed that adding amiloride to HCTZ lowered the levels of stone-forming salts (brushite and calcium oxalate) in urine. This reduces the likelihood of kidney stone formation.

📄 Summary of HCTZ vs. Potassium-Sparing Diuretics

Based on the findings above:

➤ Blood Pressure Control: HCTZ lowers blood pressure more effectively than potassium-sparing diuretics alone. However, they are often combined to enhance effectiveness and minimize potassium loss.

➤ Potassium Levels: HCTZ causes greater potassium loss, so it is often combined with potassium-sparing diuretics to reduce this risk.

➤ Heart Health: Eplerenone and spironolactone may improve blood vessel flexibility and circulation. HCTZ, especially with amiloride, reduces stroke risk and heart-related issues.

➤ Kidney Health: Amiloride with HCTZ improves kidney function by helping maintain blood flow to the kidneys and reducing kidney stone formation.

The Bottom Line

Hydrochlorothiazide and other thiazide diuretics remain common choices for managing hypertension. Among them, chlorthalidone and indapamide have been shown to lower blood pressure more effectively than HCTZ.

Compared to loop diuretics, HCTZ is generally more effective, though loop diuretics are primarily used for fluid buildup from conditions like heart failure.

Potassium-sparing diuretics help counteract HCTZ’s potassium-lowering effects. While these medications alone do not lower blood pressure as effectively, they can be combined with HCTZ for better results.

Your choice between HCTZ vs. other diuretics depends on your overall health, current medical conditions, and potential risk factors. Consistent monitoring helps maximize treatment benefits and reduce the risk of side effects.

FAQs on HCTZ vs. Other Diuretics

What is the most preferred diuretic?

Based on current medical guidelines, thiazide diuretics are the preferred choice for managing high blood pressure, with HCTZ being the most commonly prescribed. While some studies suggest that chlorthalidone may be more effective than HCTZ, other trials found no significant difference between them.

Which is the safest diuretic?

The safest diuretic depends on your medical history, existing health conditions, and other medications you’re taking. For instance, if you have gout, certain diuretics may not be ideal as they can raise uric acid levels, increasing the risk of an attack. Those with reduced kidney function may also require careful selection to avoid complications. If your healthcare provider prescribes a diuretic, discuss why it was chosen to ensure it aligns with your specific health needs.

What is the strongest natural diuretic?

There is no research definitively identifying a single natural diuretic as the “strongest.” However, several studies have examined the diuretic effects of Equisetum arvense (field horsetail). One study found that it produced a diuretic effect comparable to HCTZ without significantly altering electrolyte levels. Other potent natural diuretics include coffee, dandelion, and parsley.

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