Reperfusion Therapy in Acute Myocardial Infarction

Introduction

Acute myocardial infarction (AMI) represents a critical cardiovascular emergency characterized by the sudden occlusion of a coronary artery due to thrombus formation on a ruptured or eroded atherosclerotic plaque. Prolonged ischemia leads to irreversible myocardial necrosis, making time-to-reperfusion the single most important determinant of survival and long-term outcomes.

Reperfusion therapy—either via thrombolysis (fibrinolysis) or primary percutaneous coronary intervention (PCI)—has revolutionized the management of ST-segment elevation myocardial infarction (STEMI). By restoring blood flow, reperfusion limits infarct size, preserves left ventricular function, and reduces mortality. However, each strategy carries unique indications, benefits, risks, and logistical considerations.

This article explores the principles and practice of reperfusion therapy, focusing on thrombolysis, PCI, timing strategies, and post-procedural care.

Thrombolysis

1. Indications

Thrombolysis, also called fibrinolytic therapy, is indicated primarily in STEMI when timely PCI is unavailable. Key indications include:

STEMI within 12 hours of symptom onset if PCI cannot be performed within recommended timeframes.
Persistent ST-segment elevation or new left bundle branch block (LBBB) consistent with acute infarction.
Cardiac arrest survivors with STEMI when immediate PCI is not feasible.

Beyond 12 hours, thrombolysis may be considered if there is ongoing ischemia, but benefit diminishes with time.

2. Contraindications

Absolute Contraindications:

Prior intracranial hemorrhage.
Known intracranial neoplasm, AV malformation, or aneurysm.
Ischemic stroke within the past 3 months.
Active internal bleeding.
Suspected aortic dissection.

Relative Contraindications:

Uncontrolled hypertension (>180/110 mmHg).
Recent major surgery or trauma.
Active peptic ulcer.
Pregnancy or recent postpartum period.
Current anticoagulation with high INR.

3. Agents

Modern fibrinolytic agents fall into fibrin-specific and non-fibrin-specific categories.

Non-fibrin-specific:
- Streptokinase: First widely used, low cost, but high antigenicity and systemic fibrinolysis.
Fibrin-specific (preferred):
- Alteplase (tPA): Recombinant tissue plasminogen activator, requires weight-based infusion.
- Reteplase (rPA): Bolus administration, simpler dosing.
- Tenecteplase (TNK-tPA): Single bolus, high fibrin specificity, more convenient in emergency settings.

Tenecteplase and reteplase are often preferred in modern practice due to ease of administration.

4. Complications

While thrombolysis saves lives, it is associated with significant risks:

Intracranial hemorrhage (ICH): The most feared complication, risk increases with age, hypertension, and low body weight.
Major bleeding: Gastrointestinal or retroperitoneal.
Allergic reactions and hypotension: Particularly with streptokinase.
Reperfusion arrhythmias: Ventricular tachyarrhythmias due to sudden restoration of blood flow.
Failed reperfusion: ~30–40% of cases show inadequate ST resolution, requiring rescue PCI.

Percutaneous Coronary Intervention (PCI)

1. Overview

Primary PCI involves mechanical reopening of the infarct-related artery using balloon angioplasty, stent implantation, and adjunctive pharmacotherapy. It is considered the gold standard for reperfusion when performed promptly by experienced teams.

2. Indications

STEMI within 12 hours of symptom onset when PCI can be performed within guideline-recommended times.
Cardiogenic shock or acute severe heart failure, regardless of time from onset.
Contraindication to thrombolysis.
Failed fibrinolysis (“rescue PCI”).
Post-thrombolysis ischemia or re-infarction (“pharmaco-invasive strategy”).

3. Advantages Over Thrombolysis

Higher rates of complete reperfusion (TIMI 3 flow).
Lower risk of recurrent ischemia, reinfarction, and stroke.
Better outcomes in elderly patients and those with large infarcts.
Direct visualization of coronary anatomy, allowing revascularization of non-culprit lesions if necessary.

4. Limitations

Requires specialized facilities and expertise.
Delays due to transfer times reduce effectiveness.
Procedure-related complications:
- Coronary dissection or perforation.
- No-reflow phenomenon.
- Access-site bleeding or vascular injury.

Timing: Door-to-Balloon vs. Fibrinolysis

“Time is muscle” remains the guiding principle in reperfusion. The benefit of any strategy depends largely on how quickly blood flow is restored.

1. Door-to-Balloon Time

Defined as the time from first medical contact (FMC) or hospital arrival to first balloon inflation or stent deployment during PCI.
Goal: ≤90 minutes from FMC (ideally <60 minutes in PCI-capable centers).
Each 30-minute delay in reperfusion increases 1-year mortality by ~7%.

2. Door-to-Needle Time

For fibrinolysis, the goal is ≤30 minutes from hospital arrival to administration of the agent.
Best outcomes occur when given within the first 2–3 hours of symptom onset.

3. Strategy Selection

If PCI can be performed within 90–120 minutes of FMC: Primary PCI is preferred.
If PCI will be delayed >120 minutes: Immediate fibrinolysis is recommended, followed by:
- Rescue PCI if lysis fails.
- Routine angiography and PCI within 2–24 hours (pharmaco-invasive approach).

4. Special Scenarios

Rural/remote settings: Thrombolysis followed by transfer (“drip-and-ship” approach).
Pre-hospital fibrinolysis: Administered by trained emergency teams to reduce delays.
Shock/unstable patients: Direct transfer to PCI center regardless of time delays.

Post-Procedural Care

Successful reperfusion is not the end of therapy; optimal post-reperfusion care is essential to improve survival, prevent complications, and reduce recurrence.

1. Antiplatelet Therapy

Aspirin: Lifelong therapy unless contraindicated.
P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor): Dual antiplatelet therapy (DAPT) for at least 12 months post-PCI.
Glycoprotein IIb/IIIa inhibitors: Occasionally used during PCI in high thrombus burden.

2. Anticoagulation

During PCI: unfractionated heparin or bivalirudin.
During fibrinolysis: enoxaparin or fondaparinux may be used alongside lytics.

3. Adjunctive Medical Therapy

Beta-blockers: Reduce myocardial oxygen demand, decrease arrhythmias, improve survival.
ACE inhibitors/ARBs: Initiated early in LV dysfunction or anterior MI, prevent remodeling.
Statins (high-intensity): Initiated immediately, irrespective of baseline LDL.
Aldosterone antagonists: In patients with LV dysfunction and heart failure.
Nitrates and morphine: For symptomatic relief.

4. Monitoring and Complications

Reperfusion arrhythmias: Transient accelerated idioventricular rhythm is common.
Bleeding complications: Especially with DAPT and anticoagulation.
Stent thrombosis: Rare but catastrophic, requires adherence to DAPT.
Heart failure and remodeling: Echocardiography for assessment of LV function.

5. Secondary Prevention and Rehabilitation

Lifestyle modification: Smoking cessation, diet, exercise, weight control.
Risk factor management: Hypertension, diabetes, dyslipidemia.
Cardiac rehabilitation: Structured exercise and education programs.
Patient education: Adherence to medications, recognition of warning symptoms.

Future Directions

Pharmacoinvasive strategies: Standardizing thrombolysis followed by early PCI in resource-limited settings.
Novel fibrinolytics: Agents with better fibrin specificity and lower bleeding risk.
Microvascular reperfusion therapies: Drugs or devices to address no-reflow phenomenon.
AI-driven triage: Optimizing patient selection for PCI vs fibrinolysis based on geography and clinical profile.