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Source/Disclosures Posted by: Source: Mentz R. LBS.01: The Main Event: Changing Clinical Practice. Presented at: American Heart Association Scientific Sessions; November 5-7, 2022; Chicago (hybrid meeting). Disclosures: Mentz reports receiving research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis , Novo Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics and Zoll. Bozkurt reports consulting for Amgen, Baxter, Bristol Myers Squibb, Relypsa, Sanofi Aventis, and scPharmaceuticals, serving on the clinical events committee for an Abbott-sponsored trial, and serving on the data safety monitoring committee for a LivaNova-sponsored trial .
ADD SUBJECT TO EMAIL NOTIFICATIONS Receive an email when new articles are published Enter your email address to receive an email when new articles are published on . ” data-action=subscribe> Subscribe We were unable to process your request. Please try again later. If you continue to experience this problem, please contact [email protected] Back to Healio CHICAGO — A torsemide versus furosemide treatment strategy did not improve long-term clinical outcomes for adults hospitalized with heart failure, including all-cause mortality and all-cause hospitalizations, researchers reported. Furosemide is the most commonly used loop diuretic for the management of fluid retention in heart failure. However, torsemide may offer more advantages, said Robert J. Mentz, MD, associate professor of medicine and population health at Duke University School of Medicine, during a news conference at the American Heart Association’s Scientific Sessions. Robert J. Mentz “[Torsemide] it has more consistent oral bioavailability, meaning absorption may be better, particularly in conditions of volume overload for our heart failure patients,” Mentz said. “It also has a longer duration of action than furosemide. In addition, it has anti-aldosterone and anti-fibrotic effects, and previous observational studies have suggested potential outcome benefits. However, without a strong, randomized clinical trial, it is unknown whether torsemide improves clinical outcomes compared with furosemide.”
Diverse, real cohort
For TRANSFORM-HF, a pragmatic comparative effectiveness study, Mentz and colleagues analyzed data from 2,859 patients hospitalized with heart failure between 2018 and March 2022. Eligibility criteria were broad to allow for more diverse recruitment, Mentz said. Patients were eligible regardless of ejection fraction as long as there was a long-term plan for a loop diuretic. The average age of the participants was 65 years. 37% were female and 34% were black. 30% of patients had newly diagnosed heart failure and two-thirds had HF with reduced EF. The researchers randomly assigned patients to an open-label diuretic strategy of torsemide or furosemide, with dosing per routine physician. Participants continued routine clinical follow-up without in-person study-specific visits. The primary endpoint was all-cause mortality, which was chosen based on previous meta-analyses that suggested a reduction in mortality with torsemide versus furosemide, Mentz said. “Our hypothesis was that torsemide would reduce mortality by 20% compared to furosemide,” Mentz said. At a median follow-up of 17.4 months, 26.2% of participants in the furosemide group and 26.1% of participants in the torsemide group died, for an HR of 1.02 (95% CI, 0.89-1, 18, P = 0.077) “These data were consistent across all prespecified subgroups,” Mentz said during the press conference. Event rates were also similar for the secondary endpoint of all-cause mortality or all-cause hospitalization at 12 months, with 49.3% of patients in the furosemide arm and 47.3% of patients in the torsemide arm experienced one event, for an HR of 0.92 (95% CI, 0.83-1.02, P = 0.011). The ratio of total hospitalizations at 12 months was 0.94 (95% CI, 0.84-1.07). During a presentation, Mentz said the all-cause results may have been “too imprecise” to measure differences, especially during the COVID-19 pandemic. Future work will characterize how nonadherence and dose may have influenced the findings. “There were a number of important lessons we learned about realistic trial design and execution,” Mentz said. “Broad eligibility criteria and an improved study protocol integrated into routine care supported the inclusion of diverse participants, with 37% women and 34% self-identified black. Pragmatic evidence reduced traditional barriers to patient and site participation and supported robust recruitment, even during the COVID-19 pandemic. This real-world, comparative effectiveness study provides generalizable results that apply to our patients.” Mentz said clinical time should be spent ensuring heart failure patients are prescribed the correct dose of their loop diuretic and prioritizing treatments that are proven to improve clinical outcomes.
“challenge endpoint” of all-cause mortality
Biykem Bozkurt In a discussion after the presentation, Biykem Bozkurt, MD, PhD, The Mary and Gordon Cain Chair and Professor of Medicine and director of the Winters Center for Heart Failure Research at Baylor College of Medicine, noted that all-cause mortality is “very challenging endpoint’ for any trial, especially during the COVID-19 pandemic. Alternative disease-specific endpoints, such as HF death or HF hospitalization, may better reflect potential differences in the strength of decongestion in HF and mechanistic differences in CVD, Bozkurt said. “The results probably won’t change clinical practice,” Bozkurt said. “Clinicians will likely continue to use torsemide according to their judgment, especially for bioavailability and diuretic potency when desired, especially for people who are diuretic resistant. However, pragmatic tests are very important for their simplicity, cost-effectiveness and reflection of a real-world environment with diversity. It would be so great if we could find a middle ground between real experimental design in real trials and look at the mechanisms and capture these other intermediate endpoints.”
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