Review of Head and Neck Cancer

# Review of Head and Neck Cancer *Published: 2026 May 11* print. Digoxin in Patients With Symptomatic Rheumatic Heart Disease: A Randomized Clinical Trial. Karthikeyan G(1)(2), Devasenapathy N(3)(4), Ghosh A(3)(4)(5), Kini PR(6), Varyani R(6), Satheesh S(7), Gupta MD(8), Palleda GM(8), Sethi R(9), Yadav S(1), Asotra S(10), Gopalakrishnan A(11), Kapoor A(12), Meena CB(13), Math RS(14), Bansal S(15), Senguttuvan NB(16), Biswas S(3), Rastogi A(3), Soni M(3), Jha V(3)(5)(17), Jhajhria R(2), Kaushik B(2), Wadhwa N(2); Dig-RHD Investigators. Collaborators: Singh S, Siddharthan D, Parakh N, Naik N, Purohit G, Priya C, Bansal N, Sharma A, Shukla M, Gupta A, Sahu AK, Singh A, Gupta A, Pradhan A, Bhandari M, Vishwakarma P, Tiwari N, Singh A, Selvaraj RJ, V SB, Subrahmanyam D, M V, Arya AB, Narayanappa S, Narasimhappa S, Nataraj N, Sharma R, Kumar R, Rana S, P VC, Rolston D, Kumar S, Bhuvneshwari G, Gupta P, Gupta P, Munjal M, Prabhakaran D, Kothari SS, Kailasam S, Krishnan A, Xavier D, Negi PC, Dwivedi SK, M J, Abraham V, Thakur JS, Sharma M, Singh P, Kumar RA, Fung E, Pandey RM, John P, Dass A. Author information: (1)Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi, India. (2)Translational Health Science and Technology Institute, Faridabad, Haryana, India. (3)The George Institute of Global Health, New Delhi, India. (4)Prasanna School of Public Health, Manipal Academy of Higher Education, Karnataka, India. (5)University of New South Wales, Sydney, Australia. (6)Department of Cardiology, Sri Sathya Sai Institute of Higher Medical Sciences, Bengaluru, India. (7)Department of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India. (8)Department of Cardiology, Govind Ballabh Pant Hospital, New Delhi, India. (9)Department of Cardiology, King George's Medical University, Lucknow, India. (10)Department of Cardiology, Atal Institute of Medical Super Specialties, Indira Gandhi Medical College, Shimla, India. (11)Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India. (12)Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. (13)Department of Cardiology, Sawai Man Singh Medical College, Jaipur, India. (14)Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, India. (15)Department of Cardiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. (16)Department of Cardiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India. (17)Faculty of Medicine, Imperial College London, London, United Kingdom. Comment in doi: 10.1001/jama.2024.8258. doi: 10.1001/jama.2026.7462. doi: 10.1001/jama.2026.7886. ## IMPORTANCE Heart failure is the most common cause of death in patients with rheumatic heart disease. The efficacy and safety of digoxin in this population are not known. ## OBJECTIVE To determine if digoxin, compared with placebo, improves the composite of death or new-onset or worsening heart failure in patients with symptomatic rheumatic heart disease. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, placebo-controlled trial enrolling patients with rheumatic heart disease who additionally had heart failure or atrial fibrillation or were already taking digoxin at 12 tertiary care hospitals in India between February 25, 2022, and August 31, 2024; median follow-up was 2.1 years (until December 15, 2025). ## INTERVENTIONS Patients were randomized in a 1:1 ratio, stratified by baseline rhythm, to receive oral digoxin, 0.125 to 0.25 mg once daily (n = 885), or matching placebo (n = 884). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of all-cause death or new-onset or worsening heart failure within 36 months of follow-up or until study end, whichever occurred first. Key secondary outcomes were all-cause death, new-onset or worsening heart failure, and a composite of heart failure-related death or new-onset or worsening heart failure. ## RESULTS Of 1769 enrolled patients, 1759 took at least 1 dose of the study medication and were included in the primary analysis. The mean age was 46 years and 72% were female. Most patients (81.5%) had mixed lesions involving multiple valves, with 85% having moderate to severe mitral stenosis. Atrial fibrillation was present in 70%, and 90% were in New York Heart Association class II to IV. The primary composite outcome occurred in 276 patients (31.4%) receiving digoxin and 312 (35.5%) receiving placebo (hazard ratio, 0.82; 95% CI, 0.70-0.97; P = .02). New-onset or worsening heart failure occurred in 227 patients (25.8%) receiving digoxin and in 257 (29.2%) receiving placebo (hazard ratio, 0.82; 95% CI, 0.69-0.98). Most episodes of worsening heart failure were treated with augmentation of oral or intravenous diuretics without hospitalization. Death from any cause occurred in 88 patients (10%) receiving digoxin and 91 (10.4%) receiving placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26). Ten patients receiving digoxin (1.1%) and 1 receiving placebo permanently discontinued study medication due to suspected digoxin toxicity. CONCLUSIONS AND RELEVANCE In patients with symptomatic rheumatic heart disease, digoxin reduced the risk of a composite of all-cause death or new-onset or worsening heart failure, with little risk of toxicity. ## TRIAL REGISTRATION CTRI Identifier: CTRI/2021/04/032858. DOI: 10.1001/jama.2026.7335 PMCID: PMC13158856 DOI: 10.1001/jama.2026.3735