Dipyridamole
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Dipyridamole: From Atrial Fibrillation to Prinzmetal Angina
One-Sentence Summary
Dipyridamole is an antiplatelet and vasodilator drug, listed in the knowledge graph under the original indication of atrial fibrillation. The TxGNN model's top-ranked prediction is Prinzmetal angina, but no clinical trials are registered for it and the 11 publications retrieved are mostly diagnostic stress-test studies and case reports. By contrast, the second- and fifth-ranked predictions (stroke and transient ischaemic attack) are already established uses, backed by 8 and 2 registered trials respectively and several meta-analyses.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atrial fibrillation (from the knowledge graph; the Singapore licences list no approved indication text) |
| Predicted New Indication | Prinzmetal angina |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L4 (for Prinzmetal angina) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
For context, the other leading predictions are:
| Predicted Indication | Score | Evidence Level | Decision |
|---|---|---|---|
| Stroke disorder | 99.95% | L1 | Proceed with Guardrails |
| Thrombotic disease | 99.94% | L3 | Research question (needs a defined subtype) |
| Transient ischemic attack | 99.87% | L1 | Proceed with Guardrails |
| Seven others (rare genetic syndromes, sinus thromboses) | 99.7–99.9% | L5 | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, dipyridamole inhibits adenosine reuptake and phosphodiesterase activity. This raises adenosine and cyclic nucleotide (cAMP/cGMP) levels, which causes coronary vasodilation and inhibits platelet aggregation.
Prinzmetal angina (top prediction): The mechanism does not clearly support benefit here. In the retrieved literature, dipyridamole appears mainly as a stress-testing agent (thallium imaging, echocardiography). One study (PMID 3421166) suggests that stopping dipyridamole stress with aminophylline can trigger coronary vasospasm in variant angina. This points to a possible risk rather than a therapeutic benefit. Vasospastic angina is mainly managed with calcium channel blockers and nitrates.
Stroke and TIA: The antiplatelet mechanism is directly relevant. Aspirin plus dipyridamole is a recognised option for secondary stroke prevention. However, this is an established indication, not a novel repurposing finding.
Thrombotic disease: The antiplatelet action is plausible, but the evidence is mostly older reviews, and several retrieved papers are off-target.
Rare genetic syndromes: For sick sinus syndrome 2, sarcoglycanopathy, Wildervanck syndrome and the macrocephaly syndrome, no mechanistic rationale is evident. For sick sinus syndrome, raised adenosine could in theory worsen bradyarrhythmia.
Clinical Trial Evidence
No clinical trials are registered for the top-ranked prediction, Prinzmetal angina. The most relevant trials, for the established stroke/TIA indications, are listed below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00161070 | Phase 4 | Completed | 4500 | ESPRIT: aspirin plus dipyridamole or mild anticoagulation vs aspirin alone after TIA or minor stroke of arterial origin (directly relevant) |
| NCT00562588 | Phase 4 | Completed | 551 | EARLY: Aggrenox started within 24 hours of stroke vs after 7 days of aspirin |
| NCT00238667 | Phase 3 | Completed | 250 | CADISS: antiplatelet vs anticoagulant therapy in cervical artery dissection (dipyridamole only part of the antiplatelet arm; indirect) |
| NCT00562289 | Phase 3 | Completed | 664 | PFO closure vs anticoagulants vs antiplatelets for stroke recurrence (indirect) |
| NCT00738894 | N/A | Completed | 664 | Gore REDUCE: PFO closure device plus antiplatelet therapy (dipyridamole is not the intervention) |
| NCT02630862 | N/A | Completed | 240 | Oxidative stress biomarkers with aspirin plus dipyridamole after carotid revascularisation (low relevance) |
| NCT06053021 | N/A | Unknown | 1200 | Antiplatelet therapy in acute ischaemic stroke with thrombocytopenia (no confirmed dipyridamole-specific role) |
| NCT06983795 | N/A | Not yet recruiting | 1000 | Asia-Pacific registry of PFO and ischaemic stroke (no direct dipyridamole evidence) |
Literature Evidence
Prinzmetal angina (top prediction)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 633593 | 1978 | Review | Japanese Circulation Journal | Responses of 26 patients with rest angina (13 with variant angina) to several drugs including dipyridamole; propranolol tended to aggravate attacks |
| 3421166 | 1988 | Case report/Observational | American Journal of Cardiology | Aminophylline termination of dipyridamole stress can trigger coronary vasospasm in variant angina |
| 3190956 | 1988 | Observational | British Heart Journal | Reproducibility of exercise testing in patients with ST elevation and different dipyridamole test responses |
| 6779029 | 1981 | Diagnostic study | Japanese Circulation Journal | Dipyridamole-loading thallium imaging for coronary disease diagnosis (66% accuracy) |
Stroke and TIA (established indications)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15569877 | 2005 | Meta-analysis | Stroke | Individual patient data meta-analysis of dipyridamole RCTs for recurrent ischaemic stroke |
| 17636684 | 2007 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Adding dipyridamole to aspirin was associated with a 22% risk reduction vs aspirin alone in one trial |
| 18535024 | 2008 | Meta-analysis | J Neurol Neurosurg Psychiatry | Aspirin plus dipyridamole vs aspirin alone after TIA or minor stroke, analysed by risk |
| 23871093 | 2013 | Meta-analysis | J Neurol Sci | Efficacy and safety of aspirin plus dipyridamole vs aspirin in secondary prevention |
| 11786451 | 2002 | Meta-analysis | BMJ | Collaborative meta-analysis of antiplatelet therapy in high-risk patients |
| 26304937 | 2015 | Meta-analysis | J Am Heart Assoc | Network meta-analysis of long-term antiplatelet therapies after stroke or TIA |
| 34211246 | 2021 | Review | Australian Prescriber | Aspirin, clopidogrel, or aspirin plus dipyridamole are first-line options for secondary stroke prevention without atrial fibrillation |
Thrombotic disease
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18174451 | 2008 | Review | Arterioscler Thromb Vasc Biol | Translational review: dipyridamole raises cAMP/cGMP and inhibits platelet-mediated thrombosis |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00470P | PERAZODIN 75 TABLET 75 mg | Tablet, sugar coated | Not stated in the data compiled |
| SIN00739P | PERAZODIN 25 TABLET 25 mg | Tablet, sugar coated | Not stated in the data compiled |
| SIN00206P | PERSANTIN INJECTION 10 mg/2 ml | Injection | Not stated in the data compiled |
All three are valid single-ingredient registrations, with oral and injectable routes available.
Safety Considerations
- Contraindications suggested by the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, thrombocytopenia, peptic ulcer disease, gastritis, hypotension, gout, hemophilia, anaemia, acute coronary syndrome, myocardial infarction, coronary thrombosis, Alzheimer disease, and others. Bleeding-related and cardiovascular conditions are the most clinically relevant.
- Drug interactions: 100 interactions were identified. Moderate-level ones include dexfenfluramine, sibutramine and fenfluramine. Others, with unclassified severity, include acetylsalicylic acid, cimetidine, omeprazole, pantoprazole, lansoprazole, metformin, glimepiride, morphine, simvastatin, prednisone and amphotericin B.
- Indication-specific cautions: In variant angina, dipyridamole may trigger vasospasm. In bradyarrhythmias such as sick sinus syndrome, raised adenosine could worsen the condition. For stroke use, the main concerns are headache, GI intolerance and bleeding risk with other antithrombotics.
Please refer to the package insert for full safety information. Label warnings and contraindications have not yet been retrieved.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, Prinzmetal angina)
Rationale:
- There are no therapeutic trials in Prinzmetal angina. The literature shows dipyridamole mainly as a diagnostic stress agent that may provoke vasospasm, and calcium channel blockers and nitrates remain the standard of care.
- Stroke and TIA have strong evidence (L1: ESPRIT plus multiple meta-analyses) and warrant Proceed with Guardrails, but they are established indications rather than new repurposing opportunities.
- Thrombotic disease is only a research question until a specific subtype is defined. The other seven predictions have no supporting evidence (L5).
To proceed, the following is needed:
- The HSA package insert warnings and contraindications (a blocking data gap for safety screening)
- Mechanism of action data from DrugBank
- Approved indication text for the three Singapore licences
- For Prinzmetal angina, a dedicated review of vasospasm risk and any prospective data before further consideration
- For stroke/TIA, confirmation of the local licensed indications and a bleeding-risk plan, particularly for co-administration with aspirin and other antithrombotics
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.