The incidence of all-cause mortality was just over 26% at a median follow-up of 17.4 months, or the same 17.0 per 1oo patient-years, for those randomly assigned to a loop diuretic during their stay in the hospital (HR 1.02, 95% CI 0.89 -1.18), Robert Mentz, MD, of Duke University Medical Center in Durham, North Carolina, reported at the American Heart Association (AHA) annual meeting. No differences were observed between groups in total subsequent hospitalizations (37.5% with torsemide vs 40.4% with furosemide, RR 0.94, 95% CI 0.84–1.07) or combined deaths and hospitalizations, either (47.3% vs 49.3% HR , 95% CI 0.83-1.02). “We were disappointed at first because we hoped there would be a significant clinical difference between these two drugs based on previous studies and clinical experience. Although we did not see better results with torsemide, these results help inform our ability to better care for people living with heart failure,” Mentz said in a news release. “Now that we have an answer to this debate, we encourage healthcare professionals to redirect time in a more patient-centered way. Instead of focusing on one loop diuretic over another, we can focus efforts on ensuring the appropriate dose of the prescribed loop diuretic and is redoubling our efforts on therapies that improve outcomes for our patients,” he said. Furosemide has historically been the most common loop diuretic used for volume management in heart failure. It remains preferred because of its familiarity and low cost in clinical practice. Torsemide, a newer but relatively inexpensive agent, is thought to work better because of its more stable oral bioavailability, longer duration of action, and other mechanistic effects — but has not been shown to be more clinically effective. AHA session discussant Biykem Bozkurt, MD, PhD, of Baylor College of Medicine in Houston, said the TRANSFORM-HF investigators may have been too optimistic in trying to show a survival benefit from torsemide when, in recent trials, linked more heart failure drugs with reduced cardiovascular death and heart failure hospitalizations specifically. In addition, Mentz’s group included the historically difficult-to-treat group of people with a preserved ejection fraction, and the overall cohort underwent extensive background guideline-directed medical therapy during the study, Bozkurt noted. Therefore, he concluded, “TRANSFORM will likely not change practice. Clinicians will likely continue to use torsemide at their own discretion, especially when better bioavailability and diuretic potency are desired, particularly in patients with diuretic-resistant heart failure.” , significant congestion and chronic kidney disease.” The trial was conducted at 60 US sites and recruitment began in 2018. Mentz and colleagues had 2,859 subjects (mean age 65 years, less than 40% women, 33% black) randomized to one of two loop diuretics in the study. The percentage with newly diagnosed heart failure was 30%. Mentz emphasized the pragmatic nature of the trial, which featured broad eligibility criteria and an improved study protocol integrated into routine care. There were no in-person study visits, and researchers relied on telephone follow-up and national death records. Before inclusion, 67% of participants were taking a loop diuretic, mainly furosemide, with a total daily dose of 66 mg furosemide equivalent. The total daily dose was increased to approximately 80 mg furosemide equivalent at discharge, after local clinicians were given room to decide on the diuretic dosage for each patient. As TRANSFORM-HF was conducted open-label, it was possible that bias may have caused medication changes during the study. Crossover and diuretic discontinuation occurred in both furosemide and torsemide users. However, Mentz reported that the main findings remained in the on-treatment analysis of people taking their assigned medication at discharge and for 30 days. As the trial was conducted during the pandemic, the all-cause findings may also have been affected by COVID-19. In addition, the trial did not assess decongestion or adverse events such as worsening renal function, electrolyte abnormalities, or non-hospitalization events. Revelations TRANSFORM-HF was supported by the National Heart, Lung, and Blood Institute. Mentz disclosed relationships with Abbott, Boehringer Ingelheim/Lilly, Cytokinetics, Amgen, AstraZeneca, Bayer, InnoLife, Merck, Novartis, Sanofi/Lexicon, Vifor, GlaxoSmithKline, American Reagent, Medtronic, Zoll, and Windtree. Bozkurt disclosed relationships with Bristol Myers Squibb, scPharmaceuticals, Baxter Health Care, Sanofi Aventis Pharmaceuticals, Relypsa, Respicardia, Abbot Vascular, and Liva Nova.
