Definition and pathophysiological rationale
ST-segment elevation myocardial infarction (STEMI) is a working diagnosis based on persistent ST-segment elevation or an equivalent electrocardiographic pattern in a patient with symptoms of myocardial ischaemia. The immediate therapeutic objective is restoration of coronary blood flow to the infarct zone, thereby limiting infarct size and preserving myocardial function.
The benefit of reperfusion is strongly time-dependent. The interval from symptom onset to reperfusion is determined by patient recognition and help-seeking, pre-hospital assessment and transport, diagnostic and treatment delays, and the time required for the selected treatment to restore flow. Early reperfusion is therefore the central priority of STEMI systems of care.
Fibrinolysis promotes thrombus dissolution by converting plasminogen to plasmin. Fibrin-specific agents act preferentially when fibrin is present, whereas streptokinase is not fibrin-specific and produces more extensive fibrinogen depletion. Successful fibrinolysis is generally accompanied by relief of ischaemic symptoms, at least 50% resolution of ST-segment elevation, and haemodynamic stability.
Selection of the reperfusion strategy
Primary PCI as the preferred strategy
Primary percutaneous coronary intervention (PPCI) is preferred to fibrinolysis when the anticipated interval from STEMI diagnosis to PCI-mediated reperfusion is less than 120 minutes. When treatment delay is similar, PPCI reduces mortality, non-fatal reinfarction, and stroke compared with fibrinolysis. It is also more effective at opening the occluded coronary artery and is advantageous when fibrinolysis is contraindicated, bleeding risk is high, the diagnosis is uncertain, cardiogenic shock is present, or symptoms have been present for more than 2–3 hours.
Patients with a working diagnosis of STEMI should, whenever possible, be transported directly to a hospital with 24/7 PCI capability, bypassing non-PCI hospitals. A regional network should link emergency medical services, non-PCI hospitals, PCI centres, intensive care facilities, and, where available, cardiothoracic and advanced haemodynamic support services.
When fibrinolysis is indicated
Fibrinolysis is indicated when:
STEMI is diagnosed or strongly suspected;
symptoms of ischaemia began within 12 hours;
timely PPCI cannot be achieved within 120 minutes of diagnosis; and
there are no contraindications to fibrinolytic therapy.
Treatment should begin as soon as possible, with a target of less than 10 minutes from STEMI diagnosis to the fibrinolytic bolus. In suitable systems, pre-hospital fibrinolysis is reasonable when it provides a substantial time saving, particularly with prolonged transport times of 60–90 minutes or more and appropriately trained medical or paramedic support capable of acquiring and transmitting a 12-lead ECG and obtaining medical authorization.
Fibrinolysis reduces mortality in patients with STEMI, with the greatest benefit when administered early. The largest absolute benefit is observed in patients at highest baseline risk, including older adults, although older patients also have more contraindications and a greater risk of bleeding and myocardial rupture.
Late presentation
For patients presenting more than 12 hours after symptom onset, PPCI is recommended when there are:
ongoing symptoms suggestive of ischaemia;
haemodynamic instability; or
life-threatening arrhythmias.
A routine PPCI strategy should be considered for presentation 12–48 hours after symptom onset. Routine PCI of an occluded infarct-related artery is not recommended when presentation is more than 48 hours after symptom onset in the absence of persistent symptoms.
Cardiogenic shock or haemodynamic instability warrants revascularization irrespective of the delay from symptom onset. PCI of the infarct-related artery is preferred; CABG is considered when PCI is not feasible or is unsuccessful. If neither PCI nor CABG is suitable or accessible, fibrinolysis may be used in the absence of contraindications.
Clinical assessment before fibrinolysis
Symptoms and clinical status
The diagnosis is based on the combination of an ischaemic clinical presentation and persistent ST-segment elevation or an equivalent ECG finding. Important features that influence treatment selection include:
duration of symptoms;
ongoing or recurrent chest pain;
evidence of heart failure;
cardiogenic shock or haemodynamic instability;
electrical instability or life-threatening arrhythmias;
bleeding risk and possible contraindications to fibrinolysis; and
the anticipated time to PCI-mediated reperfusion.
Patients with shock, acute severe heart failure, ongoing ischaemia, or significant diagnostic uncertainty generally favour a PCI-based strategy when feasible.
ECG assessment
The initial ECG establishes the working diagnosis and starts the reperfusion strategy clock. After fibrinolysis, ECG reassessment is essential. Failure of reperfusion is suggested by less than 50% ST-segment resolution within 60–90 minutes. Re-elevation of the ST segments may indicate re-occlusion or reinfarction.
Other markers of likely reperfusion include:
improvement or disappearance of chest pain;
at least 50% ST-segment resolution;
a typical reperfusion arrhythmia; and
haemodynamic stabilization.
No single clinical or ECG feature should delay transfer to a PCI-capable centre.
Assessment of fibrinolysis risk
The source material identifies intracranial haemorrhage as the most serious complication of fibrinolysis and notes that risk varies with patient characteristics and the fibrinolytic agent. Important risk factors include advanced age, low body weight, and hypertension on admission. Bleeding risk is particularly relevant in older adults, although treatment standards do not otherwise differ solely because of age.
Specific contraindications are not enumerated in the source material. Fibrinolysis should therefore be undertaken only after formal assessment for contraindications and bleeding risk.
Fibrinolytic agents
A fibrin-specific agent—tenecteplase, alteplase, or reteplase—is recommended when fibrinolysis is selected. Bolus regimens reduce administration complexity and medication errors and facilitate pre-hospital treatment.
| Agent | Regimen stated in the source material | Fibrin specificity | Fibrinogen depletion | Important considerations |
|---|---|---|---|---|
| Tenecteplase | Single weight-based intravenous bolus: 30 mg if <60 kg; 35 mg for 60–69 kg; 40 mg for 70–79 kg; 45 mg for 80–89 kg; 50 mg if ≥90 kg | ++++ | Minimal | A half-dose regimen is recommended for patients older than 75 years in the cited guidance |
| Reteplase | 10 U intravenous bolus followed by a second 10 U bolus 30 minutes later | ++ | Moderate | Convenient double-bolus administration |
| Alteplase | 15 mg intravenous bolus, followed by 0.75 mg/kg over 30 minutes, maximum 50 mg, then 0.5 mg/kg over the following 60 minutes, maximum 35 mg; total maximum 100 mg | ++ | Mild | Accelerated 90-minute infusion |
| Streptokinase | 1.5 million units intravenously over 30–60 minutes | None | Marked | Antigenic; should not be used within 6 months of previous exposure to a streptokinase product |
Tenecteplase, reteplase, and alteplase provide mortality benefits similar to one another in the cited material, while tenecteplase and reteplase offer more convenient administration than the accelerated alteplase infusion. Streptokinase remains available in some regions because it is inexpensive and effective, but prior exposure may result in antibody-mediated resistance and serious allergic reactions.
In patients aged at least 75 years, a half-dose tenecteplase regimen is recommended in the cited guidance. Older adults have a higher risk of intracranial haemorrhage and myocardial rupture; careful selection is therefore essential even though the absolute mortality benefit of reperfusion may be at least as large as in younger patients.
Antithrombotic treatment accompanying fibrinolysis
Antiplatelet therapy
Aspirin and clopidogrel are recommended with fibrinolysis.
For acute coronary syndrome more broadly, the stated aspirin regimen is:
loading dose: 150–300 mg orally, or 75–250 mg intravenously;
maintenance: 75–100 mg once daily long term.
When dual antiplatelet therapy is used, it is generally continued for 12 months unless bleeding risk is high. A proton pump inhibitor should be added when gastrointestinal bleeding risk is high.
Anticoagulation
Anticoagulation is recommended after fibrinolysis until revascularization, if performed, or for the duration of the hospital stay, up to 8 days.
Enoxaparin, given intravenously followed by subcutaneous administration, is the preferred anticoagulant in the cited recommendations. When enoxaparin is unavailable, unfractionated heparin is recommended as a weight-adjusted intravenous bolus followed by infusion.
Parenteral anticoagulation is recommended for patients with ACS at diagnosis. Anticoagulation should not be continued after the procedure unless another indication exists, such as atrial fibrillation or left ventricular thrombus.
Pharmaco-invasive management
Fibrinolysis is not a stand-alone alternative to invasive care. It should form part of a pharmaco-invasive strategy:
Diagnose STEMI and determine whether PPCI can achieve reperfusion within 120 minutes.
If not, administer fibrinolysis immediately, ideally within 10 minutes of diagnosis.
Transfer the patient immediately to a PCI-capable centre, without waiting for evidence of reperfusion.
Reassess symptoms, haemodynamics, electrical stability, and ST-segment resolution at 60–90 minutes.
Perform rescue PCI if fibrinolysis fails or the patient deteriorates.
Even after apparently successful fibrinolysis, perform angiography, with PCI if indicated, between 2 and 24 hours.
Routine early angiography after successful fibrinolysis reduces reinfarction and recurrent ischaemia compared with a watchful-waiting approach. Re-administration of fibrinolysis is discouraged when fibrinolysis has failed or re-occlusion has occurred; immediate angiography and rescue PCI are preferred.
Rescue PCI
Indications
Rescue PCI is indicated when fibrinolysis has failed or when clinical deterioration suggests persistent or recurrent coronary occlusion. The principal indications are:
less than 50% ST-segment resolution within 60–90 minutes after fibrinolytic administration;
persistent chest pain;
worsening ischaemia;
haemodynamic instability;
electrical instability;
new-onset or persistent heart failure or shock;
recurrent ST-segment elevation suggesting re-occlusion or reinfarction.
In patients with new-onset or persistent heart failure or shock after fibrinolysis, emergency angiography and PCI of the infarct-related artery are recommended when indicated.
Assessment of failed fibrinolysis
Failure should be recognized promptly rather than managed by observation alone. A practical assessment combines:
serial ECGs, particularly the degree of ST-segment resolution;
persistence or recurrence of chest pain;
haemodynamic assessment;
detection of ventricular or other life-threatening arrhythmias; and
evidence of heart failure or shock.
Less than 50% ST-segment resolution at 60–90 minutes is the specified ECG threshold for failed fibrinolysis.
Procedure and transfer
All patients receiving fibrinolysis should be transferred immediately to a PCI-capable centre. This transfer is required even when reperfusion appears successful, because early angiography is recommended within 2–24 hours. Patients with failed fibrinolysis or clinical deterioration require immediate angiography and, where appropriate, rescue PCI.
Primary PCI after fibrinolysis
After successful fibrinolysis, angiography should be performed within 2–24 hours, with PCI of the infarct-related artery if indicated. This approach is preferred to delayed angiography triggered only by recurrent symptoms, severe inducible ischaemia, left ventricular dysfunction, or outpatient testing.
The optimal exact interval within this window is not clearly defined, but the recommended range is 2–24 hours. Transfer should occur immediately after fibrinolysis so that this invasive strategy can be delivered without avoidable delay.
Procedural considerations during PCI
The cited recommendations support several technical principles:
radial access should be the default approach unless procedural considerations require otherwise;
stent implantation in the infarct-related artery during the index PPCI procedure is recommended;
drug-eluting stents are preferred to bare-metal stents;
routine thrombus aspiration is not recommended;
a routine glycoprotein IIb/IIIa inhibitor pretreatment strategy is not recommended.
Multivessel disease
The revascularization plan should be individualized according to clinical status, comorbidities, and coronary disease complexity.
In haemodynamically stable patients without shock, staged treatment of significant nonculprit disease may improve outcomes. Nonculprit PCI at the time of primary PCI may be considered in selected stable patients with uncomplicated culprit-vessel treatment, low-complexity nonculprit disease, and normal renal function.
Routine nonculprit PCI during the index procedure is not recommended in cardiogenic shock and may worsen outcomes. In shock, treatment should prioritize revascularization of the infarct-related artery; staged complete revascularization may subsequently be considered.
Cardiogenic shock and mechanical complications
Cardiogenic shock complicating STEMI is associated with high mortality and requires urgent individualized assessment. Suitable patients should undergo revascularization of the infarct-related artery by primary PCI. Routine simultaneous revascularization of nonculprit arteries is not recommended in shock.
Emergency CABG is recommended when infarct-related artery PCI is not feasible or has been unsuccessful. Emergency surgical or catheter-based repair is recommended for haemodynamically unstable mechanical complications, based on multidisciplinary Heart Team discussion.
Temporary mechanical circulatory support may be used in refractory shock that does not stabilize with other therapy, as a bridge to further decisions or advanced heart failure treatment. Routine intra-aortic balloon pump use is not recommended in ACS-related shock without mechanical complications.
Emergency CABG may also be considered when the infarct-related artery is patent but unsuitable for PCI and a large myocardial territory is jeopardized or shock is present. CABG is additionally relevant when residual coronary anatomy is unsuitable for PCI, when persistent or recurrent ischaemia remains after fibrinolysis or PCI, or when surgical repair of a mechanical complication is required.
Organization of care
Effective treatment depends on a coordinated STEMI network with common written protocols and continuous assessment of treatment times and outcomes. Emergency medical services should:
identify the working diagnosis rapidly;
obtain and transmit a 12-lead ECG where appropriate;
alert the PCI centre early;
transport directly to a 24/7 PCI-capable hospital whenever possible;
bypass the emergency department when feasible; and
initiate pre-hospital fibrinolysis when PPCI cannot be achieved within the required timeframe and a suitable system is in place.
Where transfer times make timely PPCI routinely unattainable, protocols should support rapid fibrinolysis at the point of diagnosis, followed by immediate transfer for angiography and PCI.
In-hospital monitoring
High-risk patients, including all STEMI patients and very-high-risk NSTE-ACS patients, should undergo ECG monitoring for at least 24 hours. Patients with successful reperfusion and an uncomplicated course should remain in a coronary or intensive cardiac care unit for at least 24 hours when possible, followed by an additional 24–48 hours in a monitored step-down bed.
Care should be delivered in a unit capable of managing recurrent ischaemia, severe heart failure, arrhythmias, and common comorbidities.
Complications of fibrinolysis
Intracranial haemorrhage
Intracranial haemorrhage is the most serious complication of fibrinolysis. Its reported frequency is generally less than 1%, although it varies according to clinical characteristics and the fibrinolytic agent. Case fatality is high.
Risk is increased by factors such as advanced age, low body weight, and hypertension on admission. The risk–benefit assessment is especially important in older adults.
Other bleeding
Non-intracranial bleeding is also common and may increase morbidity. Bleeding risk is increased in older patients receiving antiplatelet and anticoagulant treatment. The choice of fibrinolytic and the use of concomitant antithrombotic therapy should therefore be integrated with the patient’s bleeding and ischaemic risk.
Early hazard
Fibrinolysis may be associated with an excess of deaths during the first 24 hours, particularly in older patients treated late. Proposed contributors in the source material include myocardial rupture, fatal intracranial haemorrhage, and reperfusion injury. This early hazard is outweighed by the reduction in deaths over subsequent weeks when appropriately selected patients receive timely treatment.
Guideline recommendations
The principal recommendations are summarized below.
| Clinical situation | Recommended approach | Guideline classification stated in the source |
|---|---|---|
| STEMI with symptoms ≤12 hours | Reperfusion therapy | Class I, Level A |
| Anticipated diagnosis-to-PCI time <120 minutes | PPCI preferred to fibrinolysis | Class I, Level A |
| PPCI cannot be achieved within 120 minutes and symptoms are within 12 hours | Immediate fibrinolysis if no contraindication | Class I, Level A |
| Failed fibrinolysis, defined by ST resolution <50% at 60–90 minutes, or instability, worsening ischaemia, or persistent pain | Rescue PCI | Class I, Level A |
| STEMI presenting >12 hours with ongoing ischaemia, instability, or life-threatening arrhythmia | PPCI | Class I, Level C |
| STEMI presenting 12–48 hours after symptom onset | Routine PPCI should be considered | Class IIa, Level B |
| Occluded infarct-related artery, presentation >48 hours, no persistent symptoms | Routine PCI not recommended | Class III, Level A |
| Any patient treated with fibrinolysis | Immediate transfer to a PCI-capable centre | Class I, Level A |
| Heart failure or shock after fibrinolysis | Emergency angiography and PCI of the infarct-related artery if indicated | Class I, Level A |
| Successful fibrinolysis | Angiography and PCI if indicated within 2–24 hours | Class I, Level A |
| STEMI with cardiogenic shock | Immediate infarct-related artery angiography and PCI if indicated | Class I, Level B |
| Shock with PCI not feasible or unsuccessful | Emergency CABG | Class I, Level B |
| Shock without mechanical complications | Routine intra-aortic balloon pump not recommended | Class III, Level B |
| Anticoagulation in ACS | Parenteral anticoagulation at diagnosis | Class I, Level A |
| PCI during STEMI | Weight-adjusted intravenous UFH bolus 70–100 IU/kg | Class I, Level C |
| STEMI undergoing PPCI | Fondaparinux not recommended | Class III, Level B |
| Fibrinolysis | Aspirin plus clopidogrel and anticoagulation | Class I recommendations |
Prognosis and follow-up
Early successful reperfusion reduces infarct size and improves myocardial function and survival. Fibrinolytic therapy prevents early deaths when administered promptly to appropriately selected patients, but its benefits diminish as treatment is delayed. PPCI generally provides superior outcomes when it can be performed within the recommended time interval.
Prognosis is adversely influenced by cardiogenic shock, heart failure, life-threatening arrhythmias, mechanical complications, persistent or recurrent ischaemia, and major bleeding. Older patients may derive substantial absolute benefit from reperfusion but have greater risks of bleeding, myocardial rupture, and adverse drug effects.
Follow-up begins during the index admission with monitoring for recurrent ischaemia, re-occlusion, arrhythmia, heart failure, shock, bleeding, and mechanical complications. Patients treated with fibrinolysis require invasive assessment even after apparent reperfusion, because angiography within 2–24 hours with PCI when indicated is the recommended standard strategy. Further long-term management and secondary prevention are not detailed in the source material.
