Summary
Isosorbide Dinitrate has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Heart Failure would be drug repurposing rather than first-in-human development. This does not mean it is approved for Heart Failure. ClinicalTrials.gov lists 8 registered trials linking Isosorbide Dinitrate to Heart Failure: 8 have completed. The most advanced is Phase 4 (NCT03514108). It plans or enrolled 1100 participants. Registration activity spans 2001 to 2022. The literature layer holds 12 publications for this pair: 5 Cochrane reviews, 2 systematic reviews and 5 clinical trial publications. Publication years run from 2010 to 2023. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Heart Failure ranks 616 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Annual mortality ~22% on standard care; only 5-11% of HFrEF patients achieve normalisation of ejection fraction (HFrecEF) with GDMT; HFpEF has no disease-modifying therapy.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 78.5 (trials 28.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 8 completed, 0 other |
| Linked publications | 12 (5 Cochrane reviews, 5 clinical trial publications, 2 systematic reviews) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | ABO |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT02228408 | Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD 2017 | completed | Phase 4 | 17 |
| NCT03514108 | DANHEART (H-HeFT and Met-HeFT) 2018 | completed | Phase 4 | 1,100 |
| NCT00047775 | African-American Heart Failure Trial 2001 | completed | Phase 4 | 1,100 |
| NCT06400784 | Hypertensive Heart Failure Treatment in SSA 2022 | completed | Phase 4 | 50 |
| NCT03255512 | Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients 2017 | completed | Phase 1 | 41 |
| NCT01270139 | Plasmonic Nanophotothermal Therapy of Atherosclerosis 2007 | completed | Not applicable | 180 |
| NCT02305095 | Genomic Response Analysis of Heart Failure Therapy in African Americans 2015 | completed | Not applicable | 225 |
| NCT02627196 | Baroreflex Activation Therapy for Heart Failure 2016 | completed | Not applicable | 1,090 |
Published literature
- Cochrane review How do we define high and low dose intensity of heart failure medications: a scoping reviewKwak MJ, Wang Q, Onyebeke C et al. · BMC cardiovascular disorders · 2023 · PMID 37759279
- Cochrane review A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection FractionTromp J, Ouwerkerk W, van Veldhuisen DJ et al. · JACC. Heart failure · 2022 · PMID 34895860
- Clinical trial publication Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot TrialCharytan DM, Hsu JY, Mc Causland FR et al. · Kidney360 · 2020 · PMID 35372900
- Cochrane review New pharmacological treatments for heart failure with reduced ejection fraction (HFrEF): A Bayesian network meta-analysisLi H, Duan Y, Chen B et al. · Medicine · 2020 · PMID 32000355
- Clinical trial publication Prevention of contrast-induced nephropathy by adequate hydration combined with isosorbide dinitrate for patients with renal insufficiency and congestive heart failureQian G, Liu CF, Guo J et al. · Clinical cardiology · 2019 · PMID 30054906
- Clinical trial publication Heart Failure With Recovered Ejection Fraction in African Americans: Results From the African-American Heart Failure TrialChang KW, Beri N, Nguyen NH et al. · Journal of cardiac failure · 2018 · PMID 28918108
- Clinical trial publication Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection FractionZamani P, Akers S, Soto-Calderon H et al. · Journal of the American Heart Association · 2017 · PMID 28219917
- Clinical trial publication Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF)Sliwa K, Damasceno A, Davison BA et al. · European journal of heart failure · 2016 · PMID 27206810
- Cochrane review Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgeryZhao N, Xu J, Singh B et al. · The Cochrane database of systematic reviews · 2016 · PMID 27488764
- Cochrane review Nitrates for acute heart failure syndromesWakai A, McCabe A, Kidney R et al. · The Cochrane database of systematic reviews · 2013 · PMID 23922186
- Systematic review Heart failureMcKelvie RS · BMJ clinical evidence · 2011 · PMID 21878135
- Systematic review Heart failureMcKelvie RS · BMJ clinical evidence · 2010 · PMID 21718583
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ABO. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Isosorbide Dinitrate approved for Heart Failure?
Isosorbide Dinitrate has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Heart Failure would be drug repurposing rather than first-in-human development. This does not mean it is approved for Heart Failure. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Isosorbide Dinitrate in clinical trials for Heart Failure?
ClinicalTrials.gov lists 8 registered trials linking Isosorbide Dinitrate to Heart Failure: 8 have completed. The most advanced is Phase 4 (NCT03514108). It plans or enrolled 1100 participants. Registration activity spans 2001 to 2022.
What does the evidence show for Isosorbide Dinitrate in Heart Failure?
Isosorbide Dinitrate has both completed registered trials and synthesis-level publications linked to Heart Failure. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ABO. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.