Study Finds No Survival Differences Between Two Loop Diuretics Used in Heart Failure Patients

Affecting about 6 million Americans, heart failure (also called congestive heart failure) is a serious medical condition in which the heart cannot pump enough blood to support vital organs.[1] It often requires hospitalization and can cause death.

Joint clinical practice guidelines by the American College of Cardiology, the American Heart Association and the Heart Failure Society of America recommend treatment with loop diuretics (a type of water pills) in most heart failure patients with congestion or fluid buildup resulting in edema (swelling in body tissues, mainly in the feet, legs and ankles) or breathing difficulties.[2] Diuretics relieve these symptoms by increasing the excretion of sodium and water from the kidneys.

The most used loop diuretic for the treatment of heart failure is furosemide (LASIX and generics), which the Food and Drug Administration (FDA) approved in 1966.[3] However, torsemide (SOAANZ and generics)[4] — another loop diuretic that the FDA approved in 1993 — has been suggested to be more advantageous because it is more bioavailable (a large part of it is absorbed and used in the body) and it has a longer duration of action.[5]

Evidence from previous studies comparing furosemide and torsemide in heart failure patients was limited due to their small sample size or nonrandomized design.[6] In contrast, evidence from the first large, adequately powered randomized clinical trial that directly compared furosemide and torsemide showed that both drugs are equally effective in improving the survival of patients with heart failure.

Called the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF), the trial was funded by the National Institutes of Health; its findings were published in the Jan. 17, 2023, issue of JAMA.

About heart failure

Heart failure can develop suddenly (the acute type) or slowly over time (the chronic type) and can affect one or both sides of the heart. Most commonly, it occurs as a complication of an underlying condition, such as cardiomyopathy, coronary heart disease, heart inflammation, high blood pressure or irregular heartbeat.[7]

Initially, heart failure can be mild, causing minor symptoms that happen only with physical activity. Later, it can become severe, resulting in fatigue or tiredness, shortness of breath and edema at rest.

The goals of treatment for patients with heart failure are to improve symptoms, slow or reverse deterioration in heart function and prevent death.[8]

The TRANSFORM-HF trial[9]

This trial was an open-label, randomized clinical trial that recruited 2,859 patients (median age was 65 years) from 60 large U.S. hospitals. Of these patients, 37% were women and 34% were Black. The patients were hospitalized for either newly diagnosed heart failure or worsening of chronic heart failure (regardless of ejection fraction, which is a measure of the strength of the heart’s pumping function), and their treatment plans included daily long-term use of loop diuretics.

The researchers randomly assigned 1,431 patients to receive torsemide tablets and 1,428 patients to receive furosemide tablets while in the hospital and after discharge. Because the trial involved a pragmatic (real-world) design, the dose and frequency of the assigned loop diuretic were determined by each patient’s treating clinician. Notably, 53% of the patients in the torsemide group and 55% of those in the furosemide group had previously been treated with furosemide. After the patients were discharged from the hospital, the researchers collected follow-up data from them with telephone interviews. Rates of patient withdrawal (4%) were similar between the two drug groups.

The trial researchers hypothesized that torsemide would reduce all-cause mortality by 20% compared with furosemide. In contrast, after a median of 17 months of follow-up, they found that equal proportions (26%) of patients in both treatment groups had died, which was the primary study endpoint. After 12 months of follow-up, 38% of the patients in the torsemide group and 40% of those in the furosemide group had been hospitalized for any reason. At 12 months of follow-up, death or hospitalization occurred in comparable proportions of patients in both groups: 47% and 49% of the torsemide and furosemide groups, respectively.

The lack of additional benefit of torsemide over furosemide was consistent across various patient subgroups, including those with different demographic characteristics (including age, sex, race and ethnicity) and ejection fraction as well in patients who, at the beginning of the trial, were either newly diagnosed with heart failure or had worsening chronic heart failure.

Patient recruitment was stopped earlier than planned because the independent data- and safety-monitoring board of the trial determined that the sample size was sufficient to answer the primary research questions. Notably, the trial included patients with a range of ejection fractions, which enhances the generalizability of the findings.

What You Can Do

If you have heart failure with significant congestion requiring treatment with either furosemide or torsemide, discuss with your clinician about continuing to take either diuretic and adjusting the dosage as needed instead of switching from one drug to the other.

Because loop diuretics can cause water and electrolyte disturbances — mainly hyponatremia (low sodium levels in the blood) and hypokalemia (low potassium levels in the blood) — it is important for your clinician to use laboratory tests to monitor your electrolyte balance periodically during therapy with these drugs.[10] If you are unable to urinate, do not take torsemide or furosemide, and promptly contact your clinician.

It also is important to note that, depending on your clinical situation, symptoms and response to therapy, your clinician is likely to prescribe other medications in addition to diuretics. Examples of these medications are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or beta blockers as well as other diuretics, such as hydrochlorothiazide (MICROZIDE and generics). The TRANSFORM-HF trial only considered one aspect of treatment of heart failure: the choice of loop diuretics.

If your heart failure symptoms suddenly get worse, you should urgently contact your clinician’s office. Call 911 or seek emergency help for symptoms such as chest pain, fainting or severe weakness, rapid or irregular heartbeat and sudden severe shortness of breath.
 

References

[1] Centers for Disease Control and Prevention. Heart failure. January 5, 2023. https://www.cdc.gov/heartdisease/heart_failure.htm. Accessed August 8, 2023.

[2] Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation. 2022;145(18):e895-e1032.

[3] Validus Pharmaceuticals LLC. Label: furosemide (LASIX). February 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2c9b4d8f-0770-482d-a9e6-9c616a440b1a&type=display. Accessed August 8, 2023.

[4] Sarfez Pharmaceuticals Inc. Label: torsemide (SOAANZ). November 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213218s001lbl.pdf. Accessed August 8, 2023.

[5] Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation. 2022;145(18):e895-e1032.

[6] Kittleson MM. TRANSFORM-HFF—Can we close the loop on diuretics in heart failure? JAMA. 2023;329(3):211-213.

[7] National Heart, Lung, and Blood Institute. Heart failure. What is heart failure. March 24, 2022. https://www.nhlbi.nih.gov/health/heart-failure. Accessed August 8, 2023.

[8] Colucci WS. Overview of the management of heart failure with reduced ejection fraction in adults. UpToDate. May 23, 2023.

[9] Mentz RJ, Anstrom KJ, Eisenstein EL, et al. Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure: The TRANSFORM-HF randomized clinical trial. JAMA. 2023;329(3):214-223.

[10] Validus Pharmaceuticals LLC. Label: furosemide (LASIX). February 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2c9b4d8f-0770-482d-a9e6-9c616a440b1a&type=display. Accessed, August 8, 2023.