Hydrochlorothiazide vs. Chlorthalidone: Which Is Better and Should I Switch?

Hydrochlorothiazide (HCTZ) and chlorthalidone are both thiazide diuretics recommended as first-choice options for treating high blood pressure because of their benefits on heart health and overall death rates.

So, which one is better? Let’s look at the evidence.

  • Chlorthalidone is better at lowering blood pressure. Research shows that chlorthalidone lowers blood pressure better than HCTZ—both when the heart pumps (systolic blood pressure) and when the heart relaxes (diastolic blood pressure). In a blood pressure reading (like 120/80), systolic blood pressure is the top number (120) and diastolic blood pressure is the bottom number (80).
  • Chlorthalidone is better at lowering the risk of a cardiovascular event, such as a heart attack. Even after chlorthalidone and HCTZ achieve the same blood pressure, chlorthalidone lowers the risk of a cardiovascular event by about 20% more than HCTZ.
  • Chlorthalidone reduces the size of the left ventricle wall more than HCTZ does. In simple terms, the left ventricle is the pumping chamber of the heart, so when that chamber is working hard against high blood pressures, the muscles there can become thick and stiff (known as left ventricular hypertrophy or LVH). LVH, which occurs in about 40% of patients with high blood pressure, may lead to heart failure and increases your risk for death. Chlorthalidone appears to reduce LVH more than HCTZ does, which is a great thing.
  • Chlorthalidone has a longer duration of action. Chlorthalidone is the preferred diuretic of the American College of Cardiology because of its long duration of action (48-72 hours) and proven ability to reduce heart disease risk. The duration of action with HCTZ is short (up to only 12 hours), which means in theory, there may be portions of the day your blood pressure isn’t covered by HCTZ, whereas it would be with chlorthalidone. Many believe this is the reason chlorthalidone produces better outcomes.
  • Both drugs have similar effects on blood sugar, cholesterol, potassium, and sodium levels. Any diuretic, including HCTZ and chlorthalidone, lowers potassium levels in your blood by making you release more potassium in your urine. This can cause side effects like fatigue, muscle spasms, and abnormal heart rhythms. Some studies show that chlorthalidone lowers potassium more than HCTZ does, but the bulk of the evidence shows that both drugs cause hypokalemia (low potassium), hyponatremia (low sodium), and any changes in blood sugar and cholesterol with the same frequency. A quick set of blood tests with your doctor is required for either drug a few weeks after you start it.
  • HCTZ is available in more combination pill options. One of the main reasons HCTZ has remained so popular—despite being second to chlorthalidone in effectiveness—is its availability in different combination pills. For convenience, diuretics are sometimes paired with another hypertension medicine (an angiotensin II receptor blocker or ARB) in the same pill. With chlorthalidone, only one type of these pills exists and it’s expensive: Edarbyclor (azilsartan medoxomil/chlorthalidone). HCTZ comes in many combinations including Atacand HCT, Benicar HCT, Diovan HCT, losartan/HCTZ, and olmesartan/HCTZ.

HCTZ and chlorthalidone are both safe and cheap first-line blood pressure medications, but the evidence is clear—chlorthalidone is better.

Dr O.

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