Dihydralazine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Dihydralazine: From Hypertension to Heart Disease
One-Sentence Summary
Dihydralazine is a direct-acting arteriolar vasodilator, and it is marketed in India as an antihypertensive. The India licence records compiled for this report do not list an approved indication, so this is inferred from the drug class. The TxGNN model predicts it may be effective for heart disease, but direct evidence is weak: 1 clinical trial was found that does not clearly test this drug, and the 20 publications are mostly indirect (animal studies, small physiology studies, old reviews).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the India licence records (the drug class suggests hypertension) |
| Predicted New Indication | Heart disease |
| TxGNN Prediction Score | 0.9997 |
| Evidence Level | L4 |
| India Market Status | Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data |
| Number of Listed Products | 2 (valid: 2) |
| Recommended Decision | Hold (research question only) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, dihydralazine is an arteriolar vasodilator that lowers systemic vascular resistance and afterload. This is plausibly relevant to hypertensive heart disease, cardiac remodelling, and heart failure.
Several older publications support this indirectly. They describe dihydralazine used as a vasodilator in congestive heart failure and cardiomyopathy, and in animal models of hypertension. However, one long-term study found that its benefit in chronic heart failure faded over time.
Caution is warranted. “Heart disease” is a very broad label, and dihydralazine’s established antihypertensive use may overlap with it. The high TxGNN score may therefore partly reflect existing use rather than true repurposing. No disease-specific pivotal evidence was identified.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05230901 | Phase 3 | Unknown | 300 | Antifibrotic therapy (spironolactone, or spironolactone + dihydralazine, plus standard of care) vs standard of care alone for regression of myocardial fibrosis after TAVI in aortic stenosis |
The trial summary lists a spironolactone + dihydralazine arm, but the data do not show that dihydralazine is the primary investigational agent. It is therefore only indirect, disease-area evidence. The intervention list should be verified before the evidence level is upgraded.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29974489 | 2018 | Network meta-analysis | Br J Clin Pharmacol | Compared drugs for severe hypertension in pregnancy |
| 3075406 | 1988 | Comparative clinical study | Acta Physiol Hung | Short-term effects of captopril preparations and dihydralazine in 15 patients with severe chronic heart failure |
| 6479183 | 1984 | Placebo-controlled study | Eur Heart J | In 14 patients with severe congestive heart failure, dihydralazine lost effectiveness in long-term treatment |
| 7307999 | 1981 | Clinical study | Dtsch Med Wochenschr | Acute vasodilator effects in 16 patients with severe heart failure; only dihydralazine reduced systemic resistance acutely (by 42%) |
| 6127295 | 1982 | Review | Fortschr Med | Vasodilators including dihydralazine in the treatment of cardiomyopathies |
| 8497771 | 1993 | Review | Schweiz Med Wochenschr | Overview of hypertensive crisis |
| 42117551 | 2026 | Trial design paper | ESC Heart Fail | Design and rationale of the Reduce-MFA DZHK25 anti-fibrotic trial after TAVI |
| 1715494 | 1991 | Animal study | J Cardiovasc Pharmacol | In hypertensive rats, dihydralazine prolonged survival but did not nearly normalise it |
| 1695297 | 1990 | Animal study | J Cardiovasc Pharmacol | Haemodynamics of isradipine vs dihydralazine in atherosclerotic and normal rabbits |
| 1420010 | 1992 | Comparative study | Br J Obstet Gynaecol | Epoprostenol vs dihydralazine in severe hypertension in pregnancy |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 353 | Apresol Tablet | Strip of 15 tablets | Not stated in the records |
| 151433 | Nepresol 25mg Tablet | Strip of 10 tablets | Not stated in the records |
Safety Considerations
Please refer to the package insert for safety information. Note that the package insert warnings and contraindications could not be obtained for this report.
- Hepatotoxicity signal: Published reports describe dihydralazine-induced autoimmune hepatitis, associated with anti-CYP1A2 autoantibodies. This is a relevant safety signal for any expanded use.
- Pregnancy: The literature covers dihydralazine use in hypertensive disorders of pregnancy, including effects on the unborn child.
No drug interaction records were found.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence is limited to a model prediction plus indirect literature (mostly old, small, or animal studies), and the only trial found is not clearly testing dihydralazine. The broad “heart disease” label may simply reflect its existing antihypertensive use, and the hepatotoxicity signal argues for caution. This is best treated as a research question, not a development candidate.
To proceed, the following is needed:
- Verify the intervention list of NCT05230901 to see whether dihydralazine is a tested agent
- Define a specific cardiac indication (e.g. a particular heart failure or hypertensive heart disease population) in place of the broad “heart disease” label
- Obtain the India package insert (approved indications, warnings, contraindications) to complete safety screening
- Obtain mechanism of action data
- Prepare a hepatic safety monitoring plan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.