{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:29:00Z","timestamp":1789118940238,"version":"build-2803163510"},"reference-count":45,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/CPHS\/20\/1\/505229"],"award-info":[{"award-number":["IA\/CPHS\/20\/1\/505229"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    Background Nurse-led care supported by mobile health (mHealth) technologies offers a feasible strategy to strengthen heart failure (HF) management in resource-constrained settings. This study evaluated the impact of an mHealth-enabled, nurse-led collaborative care model on prescription of guideline-directed medical therapy (GDMT) at discharge among patients with heart failure with reduced ejection fraction (HFrEF) in India. Methods The TIME-HF study was a multicenter, open-label, cluster-randomized controlled trial conducted across 22 centers enrolling patients with HFrEF. Centers were randomized 1:1 to an intervention arm (11 centers; 755 patients) or enhanced usual care (11 centers; 752 patients). In the intervention arm, nurses used an mHealth application to review GDMT prescriptions and recommend treatment modifications to physicians. GDMT at discharge was assessed individually and using a composite score. Intervention effects were evaluated using multivariable mixed-effects logistic regression models. Results Participants were predominantly male (77.6%) with a mean age of 61.9\u00a0years (SD 12.1). Hypertension (56.1%), diabetes (62%), and chronic kidney disease (18.4%) were common comorbidities. Ischemic heart disease was the leading etiology (77.4%), and 48.8% were in NYHA class III\/IV. Baseline characteristics were similar between groups. At discharge, 20% received all four GDMT components, with higher use in the intervention group than usual care (27% vs 13%, p\u00a0&lt;\u00a00.001; adjusted OR 1.61, 95% CI 1.48\u20131.75). Intervention participants were also more likely to achieve a high GDMT score (OR 1.13, 95% CI 1.04\u20131.22). Conclusion An mHealth-supported nurse-led discharge medication review improved GDMT use in HFrEF and may help reduce preventable HF mortality in India.\n                    <ns3:bold>Trial registration: Clinical Trial Registry of India (CTRI\/2021\/11\/037797), Registered on 03\/11\/2021; the study is ongoing.<\/ns3:bold>\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.26369.1","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:49:05Z","timestamp":1779256145000},"page":"293","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhancing Guideline-Directed Medical Therapy at Discharge Through Collaborative Care: Evidence from the TIME-HF Cluster Randomized Controlled Trial"],"prefix":"10.12688","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4172-4307","authenticated-orcid":false,"given":"Panniyammakal","family":"Jeemon","sequence":"first","affiliation":[{"name":"Thiruvananthapuram Kerala Sree Chitra Tirunal Institute for Medical Sciences and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athira","family":"Thottathan","sequence":"additional","affiliation":[{"name":"Thiruvananthapuram Kerala Sree Chitra Tirunal Institute for Medical Sciences and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariyam","family":"Alex","sequence":"additional","affiliation":[{"name":"Thiruvananthapuram Kerala Sree Chitra Tirunal Institute for Medical Sciences and 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Heart J."},{"key":"ref10","article-title":"National Heart Failure Registry, India.","year":"2025 cited 2025 Jul 14"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"187","DOI":"10.4103\/HFJI.HFJI_63_23","article-title":"Guideline directed medical therapy implementation: Challenges and potential solutions.","volume":"1","author":"S Harikrishnan","year":"2023 Dec","journal-title":"Heart Failure Journal of India."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1154-1158","DOI":"10.1001\/jamacardio.2024.3023","article-title":"Global Impact of Optimal Implementation of Guideline-Directed Medical Therapy in Heart Failure.","volume":"9","author":"A Tang","year":"2024 Dec 1","journal-title":"JAMA Cardiol."},{"key":"ref13","doi-asserted-by":"crossref","first-page":"036998","DOI":"10.1161\/JAHA.124.036998","article-title":"Guideline-Directed Medical Therapy After Hospitalization for Acute Heart Failure: Insights From the CONNECT-HF.","volume":"13","author":"S Shoji","year":"2024 Dec 17","journal-title":"J. Am. Heart Assoc."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"100438","DOI":"10.1016\/j.ahjo.2024.100438","article-title":"Protocol-driven approach to guideline-directed medical therapy optimization for heart failure: A real-world application to recovery.","volume":"45","author":"C Yan","year":"2024 Sep 1","journal-title":"Am. Heart J. Plus Cardiol. Res. Pract."},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.5334\/gh.1355","article-title":"Use of Guideline-Recommended Heart Failure Drugs in High-, Middle-, and Low-Income Countries: A Systematic Review and Meta-Analysis.","volume":"19","author":"G Satheesh","year":"2024 Sep 12","journal-title":"Glob. Heart."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1202615","DOI":"10.3389\/fcvm.2023.1202615","article-title":"Remote monitoring titration clinic to implement guideline-directed therapy for heart failure patients with reduced ejection fraction: a pilot quality-improvement intervention.","volume":"10","author":"E Romero","year":"2023 Jun 19","journal-title":"Front. Cardiovasc. 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Heart Fail."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e010158","DOI":"10.1161\/CIRCHEARTFAILURE.122.010158","article-title":"In-Hospital Virtual Peer-to-Peer Consultation to Increase Guideline-Directed Medical Therapy for Heart Failure: A Pilot Randomized Trial.","volume":"16","author":"V Rao","year":"2023 Feb","journal-title":"Circ. Heart Fail."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"678-690","DOI":"10.1016\/j.jchf.2024.02.008","article-title":"The Effect of Using a Remote Patient Management Platform in Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients.","volume":"12","author":"D Brahmbhatt","year":"2024 Apr","journal-title":"JACC Heart Fail."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"197","DOI":"10.12688\/wellcomeopenres.19196.2","article-title":"Team based collaborative care model, facilitated by mHealth enabled and trained nurses, for management of heart failure with reduced ejection fraction in India (TIME-HF): design and rationale of a parallel group, open label, multi-centric cluster randomised controlled trial.","volume":"8","author":"P Jeemon","year":"2023 Jul 12","journal-title":"Wellcome Open Res."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3352-3363","DOI":"10.1002\/ehf2.14524","article-title":"A Scoring Evaluation for the Practical Introduction of Guideline-Directed Medical Therapy in Heart Failure Patients.","volume":"10","author":"R Matsukawa","year":"2023 Dec 1","journal-title":"ESC Heart Fail."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3352-3363","DOI":"10.1002\/ehf2.14524","article-title":"A Scoring Evaluation for the Practical Introduction of Guideline-Directed Medical Therapy in Heart Failure Patients.","volume":"10","author":"R Matsukawa","year":"2023 Dec 1","journal-title":"ESC Heart Fail."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e5661","DOI":"10.1136\/bmj.e5661","article-title":"Consort 2010 statement: extension to cluster randomised trials.","volume":"345","author":"M Campbell","year":"2012 Sep 4","journal-title":"BMJ."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"105108","DOI":"10.1016\/j.nurpra.2024.105108","article-title":"Improving Utilization of Guideline-Directed Medical Therapy for Heart Failure.","volume":"20","author":"G Baksh","year":"2024 Sep 1","journal-title":"J. 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Our dose-based score was intended to quantify the intensity of GDMT prescribed at discharge rather than achievement of the maximum tolerated dose.  We agree that blood pressure is an important consideration in GDMT initiation and titration; however, as our objective was to characterise the intensity of GDMT prescription at discharge, we retained the dose-based approach. Baseline information on whether participants were already receiving HF-directed treatment prior to the index admission was not collected as part of the study. Therefore, we were unable to determine the proportion of participants in each arm who were already receiving HF treatment before admission. Nurses involved in the intervention received standardised training on HF management, study procedures, data collection and use of the mHealth application before commencing their study responsibilities. Training was supported by nurse handbooks and the decision-support system within the mHealth application. Refresher training was provided during the study period to reinforce the study procedures. The same training procedures were followed when new nurses joined or replaced trained nurses, ensuring continuity and standardisation of the intervention and data collection processes.  The trial was primarily designed to evaluate the effect of the cluster-randomised collaborative care intervention and was not specifically powered to compare GDMT prescribing between government and private facilities. Since this was a cluster randomized trial with only 22 centers, it is possible for some baseline differences between the treatment groups. These variables were considered in the adjusted model, and the intervention effect remained consistent after adjustment. In TIME-HF, patients not receiving any GDMT pillar were flagged by the mHealth application, which alerted the nurse for review. The nurse then communicated with the treating physician regarding initiation of appropriate GDMT, with the final prescription determined by the physician.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/11-293\/v1#referee-comment-6717","order":1,"name":"referee-comment-6717","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.29040.r160153, Ambalam M Chandrasekaran, Centre for Chronic Disease Control, New Delhi, Delhi, 31 Aug 2026, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/11-293\/v1#referee-response-160153","order":2,"name":"referee-response-160153","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Panniyammakal Jeemon<\/b>; \n<i>Posted: 03 Sep 2026<\/i>; Thank you very much for the comments.&nbsp; &nbsp; As specified in the study protocol, consecutive patients were screened at the participating centres and assessed against the predefined eligibility criteria. The primary eligibility criterion was a standard diagnosis of heart failure with reduced ejection fraction (LVEF &lt;40%) based on echocardiography. Of the 3,034 patients screened, 1,109 were excluded for not meeting the predefined eligibility criteria, 357 declined participation, and 61 were excluded due to the absence of a smartphone. These reasons for exclusion are presented in the published participant flow diagram. &nbsp;  We would like to clarify that participants were recruited shortly before discharge and, therefore, patients who died before discharge did not meet the study inclusion criteria and were not recruited into the study. Individual patients were not randomized in this trial. As specified in the study protocol, eligible units were randomized at one time point, prior to trial implementation, in a 1:1 ratio using computer-generated random numbers. Consecutive eligible patients were subsequently recruited from the participating centres. Therefore, there were no randomized participants who died before discharge and were subsequently excluded from the study on account of death. Participant outcomes, including deaths occurring during follow-up, were accounted for according to the prespecified study procedures.  &nbsp; Given the cluster-randomized design, we do not have sufficient statistical power for meaningful subgroup analyses based on these participant- and centre-level characteristics. Such analyses would therefore be exploratory and potentially underpowered. &nbsp; We acknowledge that the predominantly southern Indian setting may have relatively higher digital penetration. However, the Government of India\u2019s Comprehensive Modular Survey: Telecom (2025) reported that 85.5% of households nationally owned a smartphone and 86.3% had internet access at home (Press Information Bureau). Although digital access is increasingly widespread, regional differences in literacy, connectivity and healthcare infrastructure may affect implementation; therefore, generalizability to substantially different settings should be interpreted cautiously. &nbsp;","URL":"https:\/\/wellcomeopenresearch.org\/articles\/11-293\/v1#referee-comment-6718","order":3,"name":"referee-comment-6718","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The work was supported by Wellcome Trust\/DBT India Alliance [IA\/CPHS\/20\/1\/505229] through a Clinical and Public Health Intermediate Fellowship to Panniyammakal Jeemon. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}