Streptokinase
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Streptokinase: From Thrombolytic Therapy to Myocardial Infarction
One-Sentence Summary
Streptokinase is a bacterial fibrinolytic enzyme historically used to dissolve blood clots in acute thromboembolic disease. The TxGNN model’s top prediction is Myocardial Infarction — but this is actually streptokinase’s classic, already-established indication rather than a novel repurposing target, and it is supported by 34 clinical trials and 20 publications, including multiple landmark Phase 3 RCTs from the 1970s–1990s.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in this evidence pack (data gap); globally, streptokinase is classically used as a thrombolytic for acute MI, deep vein thrombosis, pulmonary embolism, and arterial/graft occlusion |
| Predicted New Indication | Myocardial Infarction — Note: this is the drug’s long-established core indication, confirmed rather than newly discovered by the model (see rationale below) |
| TxGNN Prediction Score | 99.83% |
| Evidence Level | L1 |
| India Market Status | Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism-of-action data is not available in the structured record (flagged as a High-severity data gap, DG002). Based on well-established pharmacology, streptokinase is a bacterial-derived plasminogen activator: it forms a 1:1 complex with plasminogen, converting it to plasmin, which then degrades fibrin and dissolves intravascular thrombi. This is the same mechanism underlying its decades-long use as a fibrinolytic agent in acute coronary thrombosis.
Critically, the model’s top-ranked “new” indication — myocardial infarction — is not actually a novel repurposing candidate. As the evidence pack’s own rationale states, this is “the most classic and clinically established mechanism of thrombolytic agents… not a strict repurposing case but the original core indication.” Streptokinase was one of the first agents ever proven, in large RCTs (ISIS/European Working Party, GISSI-era trials, TIMI, GUSTO), to reduce mortality when given early in acute MI. TxGNN essentially re-derived a well-known clinical fact from the knowledge graph rather than surfacing new therapeutic territory.
The mechanistic rationale is nonetheless sound and directly supports coronary thrombosis (rank 4, also L1/Proceed with Guardrails) as the closest true pathophysiological correlate — coronary thrombus is the direct anatomical substrate of MI, and plasminogen activation directly resolves it. Genuinely exploratory candidates with weaker but non-trivial support include peripheral vascular disease (L2) and peripheral arterial disease (L3), reflecting the same fibrinolytic mechanism applied to non-coronary arterial thrombosis.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00000507 | Phase 3 | Completed | N/A | Landmark NIH trial testing whether early IV streptokinase limits myocardial damage in acute transmural MI |
| NCT00000505 | Phase 3 | Completed | N/A | TIMI I/II: compared streptokinase vs rt-PA thrombolytic activity and side effects in AMI; TIMI II assessed follow-on PTCA strategy |
| NCT00000503 | Phase 3 | Completed | N/A | Assessed effect of non-surgical (intracoronary) reperfusion on infarct size in AMI |
| NCT00245648 | Phase 3 | Completed | N/A | GUSTO-V: evaluated sex differences in presentation, management, and outcomes of fibrinolytic-treated AMI patients (streptokinase/tPA) |
| NCT02182011 | Phase 3 | Completed | 49 | Open-label RCT comparing procoagulant effect (TAT levels) of tenecteplase, alteplase, and streptokinase in AMI |
| NCT01305226 | Phase 3 | Completed | 120 | RCT of recombinant staphylokinase (THR-100) vs streptokinase in AMI |
| NCT00302419 | Phase 4 | Completed | 95 | Complementary intracoronary streptokinase after primary PCI improved microvascular perfusion and late infarct size |
| NCT00627809 | Phase 4 | Completed | 53 | Low-dose intracoronary streptokinase adjunct to primary PCI evaluated for effect on LV infarct size/volumes |
| NCT00968929 | Phase 4 | Completed | 83 | RCT comparing recombinant streptokinase vs urokinase for pulmonary embolism in China |
| NCT00526474 | Phase 3 | Completed | 26,449 | Large placebo-controlled trial (TRA 2°P-TIMI 50) in atherothrombotic disease, providing broader safety context for thrombolytic/antithrombotic strategies in MI prevention |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8028463 | 1994 | Meta-analysis | Medical Decision Making | Combined meta-analysis/decision analysis on how infarct location and likelihood of AMI affect cost-effectiveness of IV streptokinase |
| 2868343 | 1986 | RCT | Lancet | Landmark trial establishing efficacy of streptokinase in acute myocardial infarction |
| 2888018 | 1987 | RCT | New England Journal of Medicine | Double-blind trial (n=219) of streptokinase vs placebo within 4 hours of MI onset; improved LV function and early survival |
| 4934187 | 1971 | RCT | British Medical Journal | European Working Party controlled multicentre trial (n=730) of streptokinase vs heparin in recent MI |
| 481511 | 1979 | RCT | New England Journal of Medicine | 11-center European trial (n=2,338); streptokinase infusion significantly reduced 6-month mortality vs glucose control |
| 8005961 | 1993 | Review | J Assoc Physicians India | Review of streptokinase use in acute myocardial infarction |
| 3312370 | 1987 | Review | J Am Coll Cardiol | Review of randomized trials of intracoronary and IV streptokinase for AMI treatment |
| 21070617 | 2012 | Review | Cardiovascular Therapeutics | Review of thrombolytics for MI; traces streptokinase’s discovery through to newer plasminogen activators |
| 3815914 | 1987 | Case Report | Clinical Cardiology | Case of sequential inferolateral and anterior MI occurring during apparently successful streptokinase therapy |
| 3139173 | 1988 | Commentary | BMJ | Editorial reflecting on streptokinase thrombolysis as a milestone in MI treatment |
India Market Information
Streptokinase is currently Not Marketed in India per this evidence pack (0 registrations found). No authorization records, product names, or approved indication text are available.
Safety Considerations
Drug Interactions (122 total documented; selected major/moderate examples):
- Major risk (bleeding potentiation): Apixaban, Betrixaban, Bivalirudin, Abciximab, Acalabrutinib, Avapritinib, Deferasirox, Ibritumomab tiuxetan, Tositumomab (I-131)
- Moderate risk (additive bleeding/antiplatelet effect): Acetylsalicylic acid, Ibuprofen, Ketorolac (oral and ophthalmic), Celecoxib, Diclofenac (topical), Fenfluramine, Sibutramine, Aminocaproic acid, Omega-3 fatty acids, Ginger
Streptokinase’s fibrinolytic mechanism means concurrent use of anticoagulants, antiplatelet agents, GPIIb/IIIa inhibitors, or NSAIDs meaningfully raises hemorrhagic risk and should be managed with close clinical monitoring.
Note: TFDA/India-specific package insert warnings and contraindications are not available in this evidence pack (Blocking data gap, DG001) and must be obtained before any formal safety sign-off.
Additional Candidate Indications (Not Detailed Above)
For completeness, given this evidence pack evaluated 10 candidate indications, a brief summary of the others:
| Rank | Indication | Evidence Level | Decision | Note |
|---|---|---|---|---|
| 4 | Coronary thrombosis | L1 | Proceed with Guardrails | Direct anatomical substrate of MI; strongest mechanistic overlap |
| 8 | Peripheral vascular disease | L2 | Research Question | Same fibrinolytic mechanism, weaker/older evidence base (Cochrane review favors newer agents) |
| 9 | Peripheral arterial disease | L3 | Research Question | Shares trial evidence with PVD; no dedicated literature |
| 5 | Septal myocardial infarction | L4 | Hold | Anatomic MI subtype; literature concerns re: hemorrhagic MI association |
| 7 | Posterolateral myocardial infarction | L4 | Hold | Anatomic MI subtype; only indirect/case-level evidence |
| 2 | Prinzmetal angina | L4 | Hold | Pathology is vasospasm, not thrombosis — weak mechanistic fit |
| 6 | Posteroinferior myocardial infarction | L5 | Hold | No supporting trials or literature |
| 3 | Hemoglobinopathy | L5 | Hold | Single 1954 case report on topical enzymatic debridement; not a systemic thrombolytic use case |
| 10 | Chromosome 16p deletion | L5 | Hold | No plausible biological link; likely knowledge-graph noise |
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The core MI indication is backed by decades of Level-1 RCT evidence and is pharmacologically well-established, but a Blocking data gap (missing India-specific label warnings/contraindications, DG001) prevents completion of the S1 safety review, and the drug is currently unregistered in India.
To proceed, the following is needed:
- TFDA/India package insert PDF retrieval and parsing for warnings and contraindications (DG001, Blocking)
- Formal MOA documentation via DrugBank API query (DG002, High)
- Clarification of intended repurposing target — if the goal is genuine “new use” discovery rather than confirming the known MI indication, prioritize coronary thrombosis, peripheral vascular disease, or peripheral arterial disease for further evaluation
- India-market entry pathway assessment given current “Not Marketed” status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.