FAQs

When choosing between hydrochlorothiazide and chlorthalidone for patients with high cardiovascular (CV) risk, hydrochlorothiazide may be the more suitable option, particularly for those without a prior history of ^1,2 myocardial infarction (MI) or stroke.

Studies, including findings by Ishani et al., suggest that hydrochlorothiazide is associated with fewer adverse effects and ² remains effective in managing blood pressure.

Hydrochlorothiazide's safety profile makes it a better choice for patients at ² high CV risk without prior MI or stroke.

Conclusion

Hydrochlorothiazide is generally preferred for patients with high cardiovascular risk, especially in those without a history of MI or stroke, due to its ^1,2 favorable efficacy and safety profile.

Reference:

1. Tsujimoto T, et al. Thiazide Use and Decreased Risk of Heart Failure in Nondiabetic Patients Receiving Intensive Blood Pressure Treatment. Hypertension. 2020; 76(2):432–41.
2. Ishani A, et al. Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events. N Engl J Med. 2022 Dec 29;387(26):2401-2410

In patients at high risk of electrolyte imbalances, hydrochlorothiazide is often preferred over chlorthalidone due to its shorter duration of action, ¹ which tends to cause less severe potassium depletion.

This makes hydrochlorothiazide a safer option for those vulnerable to ¹ hypokalaemia.

Additionally, combining hydrochlorothiazide with potassium-sparing diuretics can help manage hypertension effectively while reducing the risk ¹ of electrolyte disturbances.

As compared to Chlorthalidone, hydrochlorothiazide is associated with 30% reduced risk of hyponatraemia and 2.7 times reduced risk of ² hypokalaemia.

Conclusion

Hydrochlorothiazide is preferred for patients at high risk of electrolyte imbalances due to its shorter duration of action and reduced risk of ^1,2 hypokalaemia.

Reference:

1. Clayton JA, et al. Thiazide diuretic prescription and electrolyte abnormalities in primary care. British Journal of Clinical Pharmacology. 2005;61(1):87–95.
2. Hripcsak G, et al. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med. 2020 Apr 1;180(4):542-551.

Yes, diet plays a vital role in managing electrolyte imbalances for patients on thiazide diuretics. To counteract thiazide-induced hypokalaemia, patients should incorporate potassium-rich foods like bananas, oranges, and spinach into their diet. It's equally important to manage sodium intake; maintaining a moderate sodium level is crucial, as excessive sodium can worsen fluid retention, while too little sodium may increase the risk of hyponatremia.

Proper hydration is necessary, but excessive fluid intake should be avoided to prevent electrolyte dilution. Including foods rich in magnesium and calcium also supports overall health and helps maintain electrolyte balance. Regular monitoring of electrolyte levels is essential to guide dietary adjustments, ensuring effective management of hypertension while minimizing risks.

Conclusion

Diet is essential in managing electrolyte imbalances for patients on thiazide diuretics, with an emphasis on potassium-rich foods and carefully managed sodium intake to prevent hyponatremia.

Reference:

1. Electrolytes [Internet]. Nih.gov. National Academies Press (US); 2024 [cited 2024 Aug 9]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK218740/

If patients on thiazide diuretics experience low sodium (hyponatremia) or potassium (hypokalaemia) levels, the recommended course of action involves several key steps:

1. Dose Adjustment: Start by reviewing and possibly reducing the dose of the thiazide diuretic. Switching to alternate-day dosing may minimize electrolyte imbalances while maintaining some therapeutic effect.
2. Electrolyte Supplementation: For hypokalaemia, prescribe potassium supplements or add a potassium-sparing diuretic. To manage hyponatremia, consider increasing dietary sodium or providing sodium supplements as needed.
3. Dietary Changes: Advise patients to consume a diet rich in potassium (e.g., bananas, oranges) and maintain adequate sodium intake. Ensuring proper hydration without excessive fluid intake is also important.
4. Monitoring: Implement frequent monitoring of electrolyte levels to assess the effectiveness of the adjustments and to guide further management.^1,2
5. Discontinuation: Discontinue thiazide diuretics only if these interventions fail to correct the imbalance or if the condition is severe and unresponsive to other measures.

Conclusion

Adjusting the dose, supplementing electrolytes, and making dietary changes are key steps before considering discontinuation of thiazide diuretics.^1,2

Reference:

1. Electrolytes [Internet]. Nih.gov. National Academies Press (US); 2024 [cited 2024 Aug 9]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK218740/
2. Sok K, et al. Diuretic-Associated Electrolyte Disorders in the Elderly: Risk Factors, Impact, Management and Prevention. Current Drug Safety. 2014;9(1):2–15.

Globally, hydrochlorothiazide is the most widely used thiazide diuretic due to its extensive clinical use, affordability, and broad acceptance in hypertension management. It has been available for more than 50 years and is most commonly prescribed antihypertensive drug worldwide with its presence in more than 130 million prescriptions. It has been established that monotherapy with hydrochlorothiazide has been shown to reduce CV morbidity or mortality.

Hydrochlorothiazide is recommended by multiple guidelines and has demonstrated significant benefits in reducing blood pressure and cardiovascular risk. Despite some debate and emerging alternatives, hydrochlorothiazide's long track record, safety profile, and effectiveness make it a reliable choice for many patients. As per a study by Emerson L, 2023, 25 mg of hydrochlorothiazide is used in 95% of the population.^1,2

Conclusion

Hydrochlorothiazide has more global acceptance and usage due to its long track record, affordability, and effectiveness in managing hypertension and a part of 95% thiazide diuretic combinations.^1,2

Reference:

1. Clive Rosendorff. Why Are We Still Using Hydrochlorothiazide? Journal of Clinical Hypertension. 2011;13(12):867–9.
2. Emerson L. Similar Cardiovascular Outcomes Found in Veterans Treated With Two Common Blood Pressure Medications — Chlorthalidone and Hydrochlorothiazide - U.S. Medicine [Internet]. U.S. Medicine. 2023 [cited 2024 Aug 9]. Available from: https://www.usmedicine.com/pharmacy-update/similar-cardiovascular-outcomes-found-in-veterans-treated-with-twocommon-blood-pressure-medications-chlorthalidone-and-hydrochlorothiazide/

Yes, there are notable differences in the efficacy and side effect profiles of thiazide diuretics between white and black individuals. According to a study comparing hydrochlorothiazide and chlorthalidone, both medications effectively reduce blood pressure but with some racial differences. In white patients, chlorthalidone demonstrated a greater reduction in both systolic and diastolic blood pressure compared to hydrochlorothiazide. However, more significant blood pressure reduction came with an increased risk of adverse metabolic effects, such as hypokalemia and hyperuricemia.

In black patients, chlorthalidone also provided a slightly better reduction in blood pressure than hydrochlorothiazide, but the difference was less pronounced compared to white patients. Importantly, black patients treated with chlorthalidone experienced higher rates of adverse effects, such as hypokalemia, compared to those treated with hydrochlorothiazide. Additionally, black patients on chlorthalidone were more likely to require potassium supplementation.

Conclusion

Chlorthalidone may offer superior blood pressure reduction compared to hydrochlorothiazide in both white and black patients, but it is associated with a higher risk of adverse metabolic effects, especially in black individuals. This suggests that the preference for chlorthalidone over hydrochlorothiazide may need reconsideration, particularly in black patients, due to the differences in efficacy and side effect profiles.

Reference:

1. Chekka LMS, et al. Race-Specific Comparisons of Antihypertensive and Metabolic Effects of Hydrochlorothiazide and Chlorthalidone. Am J Med. 2021;134(7):918-925.e2.

As per American Heart Association, International Society of Hypertension, Indian Society of Hypertension & European Society of Hypertension, Angiotensin receptor blockers (ARBs)+ diuretics are recommended as a first line treatment for hypertension, especially for patients with:^1-4

1. BP > 150/95 mm Hg
2. Cardiovascular risk
3. Previous stroke
4. Crucial for elderly patients

Conclusion

Guidelines recommend thiazide diuretics as a first-line treatment for hypertension, with emphasis on their efficacy in managing blood pressure.^1-4

Reference:

1. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):1269-1324.
2. Unger T, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. J Hypertens. 2020 Jun;38(6):982-1004.
3. Shah SN, et al. Indian guidelines on hypertension-IV (2019). J Hum Hypertens.2020;34(11):745-758.
4. Mancia G, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). Journal of Hypertension. 2023;41(1):1-19

Thiazide diuretics are often the first choice for hypertensive patients in specific groups as follows:

• High Cardiovascular Risk: According to a Cochrane review, diuretics are better than Calcium channel blockers (CCBs) for CV protection. Thiazide diuretics are particularly effective in patients with high cardiovascular risk. They help manage blood pressure while also reducing the risk of cardiovascular events, such as stroke and heart failure.
• Isolated Systolic Hypertension (ISH): For elderly patients with ISH, thiazide diuretics are often preferred due to their efficacy in lowering systolic blood pressure and reducing the risk of complications associated with high systolic readings.
• Patients with Edema: Thiazide diuretics are beneficial for patients who also present with edema, as they help in fluid removal, improving symptoms related to fluid retention that CCBs do not address as effectively.
• Black Patients: Thiazide diuretics are highly effective in black individuals, who often have higher blood pressure and increased salt sensitivity compared to white patients. Studies show that black patients generally respond better to thiazide diuretics, making them a preferred option in this group.
• Patients with Mild to Moderate Hypertension: For individuals with uncomplicated hypertension, especially when there are no contraindications, thiazide diuretics can be effective in lowering blood pressure and are generally well-tolerated. They also help manage conditions like heart failure and edema.
• Patients with Salt Sensitivity: Thiazide diuretics are beneficial for patients who exhibit salt sensitivity, as these medications work by increasing sodium excretion, which can help in controlling blood pressure in such individuals.
• Elderly Patients: In elderly patients, thiazide diuretics are often preferred due to their proven efficacy in reducing blood pressure and preventing stroke and cardiovascular events.^1-3

Conclusion

Thiazide diuretics are often the first choice for hypertensive patients, particularly those who are black, elderly, having cardiovascular risk, or have mild to moderate hypertension.^1-3

Reference:

1. ARMSTRONG C. JNC 8 Guidelines for the Management of Hypertension in Adults. American Family Physician. 2014 Oct;90(7):503–4.
2. Ferreira R. Thiazide diuretics in hypertension. Escardioorg [Internet]. 2024 [cited 2024 Aug 5];8(36). Available from: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-8/Thiazide-diuretics-in-hypertension
3. Reinhart M, et al. First-line diuretics versus other classes of antihypertensive drugs for hypertension. Cochrane Database Syst Rev. 2023 Jul 13;7(7):CD008161

The ideal dose of thiazide diuretics, as recommended by ACC/AHA, is crucial for achieving effective blood pressure control while minimizing side effects.

The minimum effective dose for all thiazide diuretics is 12.5 mg daily, with an optimal range of 12.5 to 25 mg.

Lower doses, such as 6.25 mg, are considered sub-optimal for effective management of hypertension and may not provide sufficient benefit.

Therefore, 12.5 mg is generally preferred as the starting dose due to its balanced efficacy and safety profile.^1-2

Conclusion

The ideal starting dose for thiazide diuretics, including hydrochlorothiazide, is 12.5 mg daily, as recommended by ACC/AHA. This dose ensures optimal efficacy while minimizing the risk of adverse effects, making it the preferred choice over sub-optimal doses or higher doses of chlorthalidone.^1-2

Reference:

1. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):1269-1324.
2. Olivas FJ, et al. Diureticsuseinthemanagementofhypertension. Hypertension. 2024;41:186-193.

In older adults with varying levels of kidney function, hydrochlorothiazide is generally preferred over chlorthalidone. A recent cohort study found that chlorthalidone was associated with a higher risk of a 30% or more decline in estimated glomerular filtration rate (eGFR), as well as a greater incidence of cardiovascular events and hypokalemia compared to hydrochlorothiazide. The risk of hypokalemia was somewhat reduced in patients with lower kidney function.

Conclusion

For patients with chronic kidney disease (CKD), hydrochlorothiazide is often preferred over chlorthalidone because it poses a lower risk of worsening kidney function and has a better safety profile for potassium levels and cardiovascular benefits.

Reference:

1. Teles F, et al. Effectiveness of thiazide and thiazide-like diuretics in advanced chronic kidney disease: a systematic review and meta-analysis. Ren Fail. 2023; 45(1): 2163903.

Chlorthalidone is associated with a higher incidence of hyperuricemia compared to hydrochlorothiazide.

Therefore, hydrochlorothiazide may be preferred for patients with a history of gout or hyperuricemia. In a study that compared the incidence of new-onset gout with diuretic therapy, the incidence of gout for the chlorthalidone group was higher than the hydrochlorothiazide group.^1,2

Conclusion

Hydrochlorothiazide is preferred for patients with a history of gout or hyperuricemia due to its lower incidence of hyperuricemia compared to chlorthalidone. ^1,2

Reference:

1. Kerndt CC, Patel P, Patel JB. Chlorthalidone [Internet]. Nih.gov. StatPearls Publishing; 2024 [cited 2024 Aug 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553174/
2. Wilson L, et al. Comparison of New‐Onset Gout in Adults Prescribed Chlorthalidone vs Hydrochlorothiazide for Hypertension. Journal of Clinical Hypertension. 2014;16(12):864–8.

For diabetic patients with hypertension, hydrochlorothiazide is often preferred due to its lower impact on glucose metabolism compared to chlorthalidone, which can exacerbate insulin resistance.

Low doses of hydrochlororthiazide are generally preferred to mitigate adverse effects while still providing therapeutic benefits.

Conclusion

Hydrochlorothiazide is often the better option for diabetic hypertensive patients due to its lower impact on glucose metabolism compared to chlorthalidone.

Reference:

1. Lin J-J, et al. Hydrochlorothiazide hypertension treatment induced metabolic effects in type 2 diabetes: a meta-analysis of parallel-design RCTs. Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2926-34.

According to IMS Rx data, an average of 67,000 HCPs have prescribed hydrochlorothiazide whereas chlorthalidone has been prescribed by 35,000 doctors, indicating that hydrochlorothiazide is more commonly used compared to chlorthalidone.

Conclusion

In India, Hydrochlorothiazide has almost double the average users than Chlorthalidone.

Reference:

1. IMS Rx – June'24

hypertension, recent analysis highlights significant differences in effectiveness:

1. Cardiovascular Events: Diuretics reduce major cardiovascular events by approximately 5% more effectively than CCBs. This means that for every 100 patients treated with diuretics, there are 5 fewer major cardiovascular events compared to those treated with CCBs.
2. Congestive Heart Failure: Diuretics are notably better at reducing the risk of congestive heart failure, with a 37% lower risk compared to CCBs. This translates to a more significant reduction in heart failure incidence among patients treated with diuretics.

As per Cochrane review wherein 90,000 participants were included, thiazide diuretics reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98) and heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82), with reduced risk of withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88), as compared to CCBs.

Conclusion

When used as first-line agents for the treatment of hypertension, thiazide diuretics decreases morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects when compared to CCBs.

Reference:

1. Reinhart M, et al. First-line diuretics versus other classes of antihypertensive drugs for hypertension. Cochrane Database Syst Rev. 2023 Jul 13;7(7):CD008161