AHA Scientific Sessions 2022 Update, Part 2: The Diuretic Wars

Volume 21, Issue 3

In last week’s issue of Talking Therapeutics, we explored 3 exciting studies presented at the recent American Heart Association annual meeting. In this week’s issue, we continue our coverage with 2 more studies that are sure to influence clinical practice for patients with cardiovascular disorders.

Torsemide Not Superior to Furosemide in Heart Failure

One of the more highly anticipated trials at the meeting was the TRANSFORM-HF trial, which compared torsemide against furosemide in patients with acute decompensated heart failure. Prior research demonstrated torsemide is not simply a more potent diuretic than furosemide, but also has potential antifibrotic properties and may even attenuate neurohormonal activation in patients with heart failure.

To test if these additional pharmacologic properties can improve clinical outcomes, the TRANSFORM-HF trial randomized nearly 3000 patients hospitalized with decompensated heart failure to furosemide vs torsemide after discharge. After a median follow up of 17 months, there were no significant differences in overall mortality or readmission to hospital, indicating torsemide is not superior to furosemide for patients with heart failure.

Chlorthalidone Not Superior to Hydrochlorothiazide for Older Adults With Hypertension

Another highly anticipated trial (coincidentally also comparing one diuretic to another) was the Diuretic Comparison Project (DCP), which randomized patients to either hydrochlorothiazide (HCTZ) or chlorthalidone. This trial aimed to compare these two diuretics against each other and to evaluate if one is superior to the other for reducing the risk of major adverse cardiovascular events.

Chlorthalidone is a more potent diuretic than HCTZ and has a longer half-life. Chlorthalidone was also the diuretic used in the pivotal ALLHAT study, which established thiazide diuretics as first-line agents for managing hypertension.

In the DCP, older adult veterans were randomized to continue taking HCTZ or to switch to chlorthalidone. Over 13,000 patients were followed for 5 years. At the end of follow up, there was no difference in the rates of major adverse cardiovascular events between the two drugs, and patients in the chlorthalidone group had higher rates of hypokalemia.

There are important caveats to this trial. It was done in a Veterans Affairs population of nearly all male, White patients. The trial was an open-label design, and most patients were taking other medications to control their blood pressure, which could have introduced confounding. Lastly, while there was a signal that chlorthalidone may provide benefit in patients with a prior history of stroke, this finding was in a subgroup analysis and is therefore only hypothesis-generating.