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Chlorthalidone Superior for Hypertension

Feb 27, 2016

New study shows medication superior to HCTZ when lowering blood pressure in patients.

Thiazide diuretics as a class are too often underused for patients with hypertension, despite how well they work with lowering blood pressure. Hydrochlorothiazide (HCTZ) at a dose of 12.5 to 25 milligrams per day is the mainstay diuretic for most prescribers, mostly due to a lack of overall knowledge regarding other diuretics within the same class, particularly chlorthalidone. Most commonly known as a thiazide-like diuretic, chlorthalidone (Thalitone®) is an inexpensive prototype diuretic used in most randomized-controlled clinical trials in the past three decades. For instance, it was used in the landmark SHEP study along with the large Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) using doses at 12.5 to 25 milligrams daily. Due to very few physicians knowing the potential of chlorthalidone versus hydrochlorothiazide, they are less likely to start patients on the medication; this unfortunately is to the disadvantage of the patient since chlorthalidone has the potential to help control their hypertension far better than the counterpart.


In a new 12-week comparative, double-blind randomized outpatient study, Dr. Anil Pareek and his team of researchers observed which of the two diuretics, HCTZ (at a dose of 12.5 milligrams) or chlorthalidone (at a dose of 6.25 milligrams) would achieve the best control in a patient’s overall blood pressure over twelve weeks of therapy. They conducted the research by using 54 patients with stage one hypertension (16 patients received chlorthalidone versus 18 who received HCTZ) and monitored their blood pressure at baseline, and then again after four and twelve weeks of therapy. What they were able to find was that with both medications, the blood pressure had lowered from baseline, both at four and twelve weeks; however, chlorthalidone was the superior of the two in achieving this. The single low dose of chlorthalidone not only reduced the overall mean 24-hour blood pressure, but the daytime and nighttime blood pressure as well. They also observed that patients on the 12.5 milligrams of HCTZ did have a lower blood pressure, but it was not significant; patients went from having sustained hypertension to masked hypertension, which can be detrimental. It is important to note that the study itself had a smaller size, which may cause it to not have the greatest amount of power; however, with the given information and the decades of research in the past, which has utilized chlorthalidone as the prime antihypertensive diuretic for clinical studies, it is undoubtedly a better choice for patients who have this condition.

Like any medications, thiazide and thiazide-like diuretics do not come without their complications and side effects. One in particular for patients to watch out for is hypokalemia, especially with increased doses, which can lead to hospitalizations and cardiovascular issues. In trials comparing the two agents, chlorthalidone has shown to have lower serum potassium concentrations than HCTZ. When combined with other agents such as an ACE inhibitor, chlorthalidone proved to be better in combination than HCTZ that had a worsening nephrotoxic effect on many individuals.

Although there is a significant amount of research on this subject, prescribers have not changed their habits when it comes to prescribing one or the other. Healthcare providers need to be made aware of the potential for chlorthalidone for patients with hypertension.

Practice Pearls:

  • Hydrochlorothiazide is the more commonly prescribed thiazide diuretic, but chlorthalidone may have greater benefits.
  • Studies have found that chlorthalidone provides greater blood pressure lowering effects over a 24-hour period than HCTZ
  • Prescribers need to be made aware of the potential for chlorthalidone for patients with hypertension.

Researched and prepared by Javeria Fayyaz, Doctor of Pharmacy Candidate LECOM of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE

Pareek, Anil K. “Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring.” Journal of the American College of Cardiology 67.4 (2016): 379-89. Web. 5 Feb. 2016.

Sakalayen, Mohammad G. “Which Diuretic Should Be Used for the Treatment of Hypertension?”American Family Physician 4th ser. 15.78 (2008): 444-46. Web. 5 Feb. 2016.

Steber, Carolyn J. “Differences in Chlorthalidone’s Mechanism of Action vs Hydrochlorothiazide and Its Clinical Relevance.” EBM Consult. N.p., Aug. 2015. Web. 05 Feb. 2016.