What is chlorthalidone used to treat?

Chlorthalidone is approved by the Food and Drug Administration (FDA) to treat hypertension and edema.¹

Multiple trials have shown chlorthalidone reduces blood pressure and associated adverse cardiovascular outcomes.^2-6 Thiazide diuretics, including chlorthalidone, continue to be listed in national and international guidelines as one of several classes of antihypertensive medications for the initial management of hypertension.^7,8 In the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, thiazide and thiazide-type diuretics are listed as primary agents for initiating antihypertensive treatment.⁹ Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers are also listed as primary agents.  

Thiazide diuretics are also recommended as part of the treatment regimen for patients with known cardiovascular disease and hypertension.^10,11 The American Heart Association (AHA), American College of Cardiology (ACC), and American Society of Hypertension (ASH) 2015 scientific statement for the treatment of hypertension in patients with coronary artery disease recommends the use of a thiazide (or thiazide-like) diuretic as part of a treatment regimen in patients with hypertension and chronic stable angina.¹⁰

The 2013 American College of Cardiology Foundation (ACCF)/AHA guidelines include thiazide diuretics in the pharmacological management of patients with heart failure.¹¹ The guideline states that while loop diuretics are preferred in most patients with heart failure, thiazide diuretics may be considered in hypertensive patients with heart failure and mild fluid retention because of their antihypertensive effects.

Non-FDA approved uses of chlorthalidone include left ventricular hypertrophy, Meniere’s disease, hypoparathyroidism, nephrolithiasis, and diabetes insipidus.^12-16

According to the 2014 American Urological Association guidelines, clinicians should offer thiazide diuretics to patients with high or relatively high urine calcium levels and recurrent calcium stones.¹³ They should also be offered to patients with recurrent calcium stones in whom other metabolic abnormalities are absent or have been addressed.

Thiazide diuretics are also sometimes used to treat Meniere’s disease, however, high quality data may still be lacking. A systematic review of thiazide use for Meniere’s disease by Crowson et al., did not identify randomized controlled trials of sufficient quality to include in their review.¹⁴ They concluded that low-level studies suggest thiazides may be beneficial in the medical management of Meniere’s disease. While the frequency of vertigo episodes improved with thiazide treatment, there was less evidence for hearing improvement.

Chlorthalidone has been used to treat some patients with hypoparathyroidism, particularly in order to avoid hypercalciuria.¹⁵ In one trial, seven patients with hypoparathyroidism were treated with chlorthalidone plus a salt-restricted diet, without added vitamin D, for up to 25 months. After 25 months, mean 24-hour calcium excretion decreased from 179 to 88 mg (p<0.001) and mean serum calcium increased from 8.2 to 9.3-mg/dL (p<0.05).

References

1. Chlorthalidone [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2017.
2. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991;265(24):3255-3264.
3. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997.
4. Five-year findings of the hypertension detection and follow-up program: I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1979;242(23):2562-2571.
5. Five-year findings of the hypertension detection and follow-up program: III. Reduction in stroke incidence among persons with high blood pressure. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1982;247(5):633-638.
6. Five-year findings of the hypertension detection and follow-up program: mortality by race-sex and blood pressure level. A further analysis. Hypertension Detection and Follow-up Program Cooperative Group. J Community Health. 1984;9(4):314-327.
7. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;31(10):1925-1938.
8. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.
9. Whelton PK, Carey RM, Aronow WS, 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2017.
10. Rosendorff C, Lackland DT, Allison M, et al. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol. 2015;65(18):1998-2038.
11. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-239.
12. Chlorthalidone. Micromedex Solutions. Truven Health Analytics, Inc. http://www.micromedexsolutions.com/chlorthalidone. Accessed July 1, 2016.
13. Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014;192(2):316-324.
14. Crowson MG, Patki A, Tucci DL. A systematic review of diuretics in the medical management of Meniere's disease. Otolaryngol Head Neck Surg. 2016;154(5):824-834.
15. Porter RH, Cox BG, Heaney D, Hostetter TH, Stinebaugh BJ, Suki WN. Treatment of hypoparathyroid patients with chlorthalidone. N Engl J Med. 1978;298(11):577-581.
16. Thirlwall AS, Kundu S. Diuretics for Meniere's disease or syndrome. Cochrane Database Syst Rev. 2006(3):CD003599.