Alteplase

證據等級: L5

預測適應症: 9 個

Alteplase: From Acute Thrombolysis to Posterolateral Myocardial Infarction

One-Sentence Summary

Alteplase is a recombinant tissue plasminogen activator (tPA), a well-established thrombolytic agent used globally for acute myocardial infarction, ischemic stroke, and pulmonary embolism. The TxGNN model predicts it may be effective for Posterolateral Myocardial Infarction — an anatomical subtype of acute MI — with a prediction score of 99.79%, supported by 3 publications but currently no dedicated clinical trials for this specific subtype. Notably, TxGNN also identifies 8 additional thrombosis-related indications, forming a coherent mechanistic cluster.

Quick Overview

Item	Content
Original Indication	Acute myocardial infarction, acute ischemic stroke, pulmonary embolism (established globally; no local license data in this pack)
Predicted New Indication	Posterolateral Myocardial Infarction
TxGNN Prediction Score	99.79%
Evidence Level	L4 (Case reports and mechanistic studies)
NL Market Status	Not available in current dataset — verify with CBG-MEB/EMA (Actilyse is EMA-authorized)
Number of Authorizations	0 (in current regulatory dataset)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Alteplase is a recombinant form of human tissue plasminogen activator (tPA). It works by binding to fibrin in a thrombus and converting the entrapped plasminogen to plasmin, which then degrades the fibrin matrix of the clot. This targeted fibrinolytic mechanism is the cornerstone of reperfusion therapy in acute thrombotic occlusion of coronary arteries, cerebral arteries, and pulmonary vasculature. Major landmark trials — GUSTO, GISSI, and TAMI — have firmly established alteplase as a standard of care for acute myocardial infarction.

Posterolateral myocardial infarction is an anatomical subtype of AMI, typically caused by occlusion of the left circumflex artery (LCx) or distal branches of the right coronary artery (RCA). The thrombolytic mechanism of alteplase is fully applicable: dissolving the culprit thrombus restores myocardial perfusion regardless of the specific coronary territory involved. In fact, large-scale RCTs like GUSTO and GISSI enrolled patients with all MI subtypes, including posterolateral infarctions, but did not report results stratified by specific anatomical location.

The TxGNN prediction is therefore mechanistically sound — it identifies a gap in formal indication labelling rather than a genuinely novel therapeutic hypothesis. The prediction score of 99.79% reflects the strong biological plausibility. The same reasoning applies to other top-ranked predictions in this evidence pack, including posteroinferior MI (rank 2, 99.79%), septal MI (rank 3, 99.77%), and coronary stenosis (rank 9, 99.14%), all of which share the common pathophysiology of coronary thrombosis.

Clinical Trial Evidence

No clinical trials specifically targeting alteplase for posterolateral myocardial infarction were identified. However, closely related trials from other predicted indications in this pack provide relevant evidence:

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00251771	N/A	Completed	209	RCT of catheter-directed venous thrombolysis for acute iliofemoral vein thrombosis — directly supports tPA use in thrombotic events (thrombophilia indication)
NCT05540834	Phase 2	Recruiting	70	VET-guided tPA treatment in critically ill patients with pro-thrombotic acute respiratory failure — personalised tPA dosing in hypercoagulable states
NCT00604695	Phase 2	Completed	40	Low-dose intracoronary tenecteplase (alteplase analogue) as adjunct during primary PCI for STEMI — supports intracoronary fibrinolytic use
NCT00868855	Phase 1	Terminated	16	Intracoronary tPA release as predictor of MACE in non-critical coronary artery disease — directly links tPA to coronary stenosis outcomes
NCT02315898	Phase 2	Completed	40	Inhaled tPA for pediatric plastic bronchitis — confirms tPA safety in paediatric populations
NCT04366778	N/A	Completed	341	TEM-tPA to detect COVID-19 patients at high thrombosis risk — validates tPA-based diagnostics in hypercoagulable states
NCT03377465	N/A	Completed	100	Biomarkers and predictors of ischemic stroke — observational study with limited direct relevance

Note: While no trials target posterolateral MI specifically, the landmark GUSTO trial (41,000+ patients) and GISSI trials included all MI subtypes. The absence of subtype-specific trials reflects clinical practice rather than lack of evidence.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
2521226	1989	RCT (Subgroup)	J Am Coll Cardiol	TAMI-1 trial: Analysed influence of infarct location on patency after 150 mg IV rt-PA; 90-min patency rates for LAD 77%, LCx 68%, RCA 68% — directly relevant to posterolateral territory
3136953	1988	Clinical Study	Circulation	Maintenance rt-PA infusion prevented coronary reocclusion and reduced late stenosis after thrombolysis in 68 AMI patients
8721695	1996	Clinical Study	Catheter Cardiovasc Diagn	Lesion-directed alteplase with intracoronary heparin in 45 unstable angina patients with coronary thrombus — multicenter prospective trial
8763515	1996	Prospective Cohort	Rev Port Cardiol	Late thrombolysis with alteplase: clarified effects on left ventricular function parameters post-MI
3121335	1987	Clinical Study	Eur Heart J	Residual coronary stenosis after rt-PA vs streptokinase: patent artery in 82% with rt-PA vs 59% with SK at 75–90 min
8480981	1993	Case Report	Ann Cardiol Angeiol	Cerebral embolism during late tPA fibrinolysis in posterolateral MI — highlights risk-benefit in this specific subtype
9502627	1998	Observational	J Am Coll Cardiol	ST elevation in posterior leads (V7–V9) identifies concomitant posterior infarction during inferior MI; these patients may benefit more from thrombolysis
31870492	2020	Clinical Study	Am J Cardiol	ICE-T-TIMI-49: Low-dose IC tenecteplase (4 mg) during PPCI — no TIMI major bleeding; supports adjunctive coronary fibrinolysis
9014973	1997	Retrospective Cohort	J Am Coll Cardiol	GUSTO sub-study: Impact of coronary revascularization surgery on survival after thrombolysis in MI
21351226	2011	Case Report	Catheter Cardiovasc Interv	Primary PCI of unprotected left main facilitated by intracoronary reteplase in posterolateral acute MI

Netherlands Market Information

No CBG-MEB marketing authorizations were identified in the current regulatory dataset for Alteplase.

Important note: Alteplase is marketed in the EU under the brand name Actilyse (Boehringer Ingelheim), authorized via the EMA decentralized procedure. It is widely available in Dutch hospitals for acute MI, ischemic stroke, and pulmonary embolism. The absence of data in this report reflects a limitation of the source dataset (Taiwan TFDA), not actual unavailability in the Netherlands. Prescribers should consult the Dutch SmPC (Samenvatting van de Productkenmerken) via the CBG-MEB Geneesmiddeleninformatiebank.

Safety Considerations

Please refer to the SmPC (Summary of Product Characteristics) for comprehensive safety information.

Known class-level considerations for tPA agents (from clinical practice):

Bleeding risk: Major haemorrhage, including intracranial haemorrhage, is the principal safety concern

Contraindications typically include: Active internal bleeding, recent (within 3 months) intracranial or intraspinal surgery/trauma, intracranial neoplasm, known bleeding diathesis, severe uncontrolled hypertension

Drug interactions: No specific DDI data was retrieved for this evidence pack. Concomitant anticoagulants (heparin, warfarin) and antiplatelet agents increase bleeding risk

The above is provided for context based on the known pharmacological profile of alteplase. Formal safety assessment requires SmPC review and should be verified through the CBG-MEB database.

All Predicted Indications Overview

The TxGNN model identified 9 indications for alteplase, forming two coherent clusters:

Cluster 1: Myocardial Infarction Subtypes (Strong Mechanistic Link)

Rank	Predicted Indication	TxGNN Score	Evidence Level	Recommendation
1	Posterolateral myocardial infarction	99.79%	L4	Proceed with Guardrails
2	Posteroinferior myocardial infarction	99.79%	L4	Proceed with Guardrails
3	Septal myocardial infarction	99.77%	L3	Proceed with Guardrails
9	Coronary stenosis	99.14%	L3	Research Question

Cluster 2: Thrombophilic/Coagulation Disorders (Moderate Mechanistic Link)

Rank	Predicted Indication	TxGNN Score	Evidence Level	Recommendation
4	Heparin cofactor 2 deficiency	99.72%	L5	Hold
5	Congenital coronary artery anomaly	99.64%	L4	Research Question
6	Factor V excess with spontaneous thrombosis	99.56%	L5	Hold
7	Antithrombin deficiency type 2	99.56%	L5	Hold
8	Thrombophilia	99.43%	L3	Research Question

Interpretation: Cluster 1 predictions represent anatomical subtypes of AMI for which alteplase is already an established treatment globally. These are “labelling gaps” rather than novel repurposing opportunities. Cluster 2 predictions involve rare coagulation disorders where alteplase addresses thrombotic complications but not the underlying deficiency — these represent genuinely novel but weaker repurposing candidates.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Alteplase’s efficacy in acute myocardial infarction is established through landmark RCTs (GUSTO, GISSI, TAMI) that included all MI subtypes. The posterolateral MI prediction reflects a labelling specificity gap rather than a novel therapeutic hypothesis. The mechanistic link is strong: fibrinolysis of the culprit thrombus in the left circumflex or distal RCA territory is fully consistent with alteplase’s proven mechanism. For the thrombophilia-related predictions (ranks 4–8), the evidence is weaker and the mechanistic rationale is limited to treating complications rather than root causes.

To proceed, the following is needed:

Verify Actilyse (alteplase) marketing authorization status via CBG-MEB Geneesmiddeleninformatiebank and obtain the Dutch SmPC
Obtain detailed mechanism of action data from DrugBank to complete the pharmacological profile
Conduct a subgroup analysis of existing large-scale AMI trials (GUSTO, GISSI) for posterolateral MI outcomes, if not already published
For thrombophilia indications: monitor NCT05540834 (Phase 2, VET-guided tPA in pro-thrombotic respiratory failure) for results expected 2026–2027
Establish a safety monitoring framework with emphasis on bleeding risk assessment in the specific patient populations

This report is generated for research purposes only and does not constitute medical advice. Drug repurposing candidates require clinical validation before application. All web pages should include YMYL (Your Money or Your Life) disclaimers.

Data cutoff: 2026-04-03 | Evidence Pack version: v4 | Candidate ID: TW-DB00009-multi

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.