Acute ST-elevation myocardial infarction: Management of fibrinolysis

INTRODUCTION — 

Patients with acute ST-elevation myocardial infarction (STEMI) should receive coronary reperfusion therapy with either primary percutaneous coronary intervention (PCI) or fibrinolysis. For most patients with acute STEMI, we prefer primary PCI rather than fibrinolysis. However, fibrinolytic therapy should be used if timely primary PCI is not available. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Approach in most patients'.)

This topic will discuss the use of fibrinolytic therapy in patients with STEMI.

The discussion of failed fibrinolysis is found elsewhere. (See "Acute ST elevation myocardial infarction: Failed fibrinolysis".)

INDICATIONS — 

All patients with STEMI who cannot receive primary percutaneous coronary intervention (PCI) in a timely manner should be considered for immediate fibrinolytic therapy (algorithm 1). The approach to choosing a reperfusion strategy based on patient characteristics and the availability of PCI is discussed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy".)

ABSOLUTE CONTRAINDICATIONS — 

Absolute contraindications to fibrinolytic therapy include prior intracranial hemorrhage, known structural cerebral vascular lesion, known malignant intracranial neoplasm, ischemic stroke within three months, suspected aortic dissection, active bleeding or bleeding diathesis, or significant closed-head or facial trauma within three months (table 1).

RELATIVE CONTRAINDICATIONS — 

Relative contraindications to fibrinolytic therapy include (table 1):

●Poorly controlled or chronic sustained hypertension (ie, systolic blood pressure >180 mmHg) [1,2]. This can be mitigated somewhat if the blood pressure is reduced prior to fibrinolytic administration.

●Ischemic stroke more than three months previously. Most patients with a history of stroke were excluded from clinical fibrinolytic trials and, in clinical practice, are less likely to receive a fibrinolytic agent. Data evaluating such patients are extremely limited. In a review of 115 patients with acute MI who had a prior nonhemorrhagic cerebrovascular event, 29 were given fibrinolytic therapy [3]. None of the 29 patients had an intracranial bleed, and these patients had a lower one-year mortality than 46 patients with a prior stroke who did not receive a fibrinolytic agent (18 versus 33 percent).

●Dementia or other intracranial pathology (except as above).

●Traumatic or prolonged cardiopulmonary resuscitation (>10 minutes) or major surgery (within <3 weeks).

●Recent (within two to four weeks) internal bleeding.

●Noncompressible vascular puncture site.

●For streptokinase, prior exposure (more than five days previously and up to one year) or prior allergic reaction to these agents.

●Pregnancy. (See "Acquired heart disease and pregnancy".)

●Active gastric ulcer.

●Current use of oral anticoagulants.

●Increased risk of intracranial hemorrhage (ICH). It has been suggested that fibrinolysis has a greater potential for harm than benefit if the risk of ICH exceeds 4 percent [4]. (See 'Stroke' below.)

●Intraocular hemorrhage from fibrinolytic therapy in patients with diabetes mellitus is rare, and diabetic retinopathy should not be considered a contraindication to fibrinolytic therapy in acute MI [5,6]. (See "Diabetic retinopathy: Prevention and treatment".)

SPECIAL POPULATIONS — 

Although concerns about the use of fibrinolytic therapy in patients with risk factors exist, we believe that the benefits of fibrinolysis outweigh the risks in most patients with the following:

Older patients — In the absence of other absolute or relative contraindications to fibrinolysis, we do not consider age alone to be contraindication to fibrinolysis.

Cardiogenic shock — The approach to choosing a reperfusion strategy in patients with cardiogenic shock is discussed separately (algorithm 1). (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Cardiogenic shock'.)

Menstruating females — For females with acute STEMI who are menstruating and in whom fibrinolytic therapy is the optimal approach to reperfusion, we use fibrinolytic therapy. In one small study, the rate of severe bleeding was not significantly increased in females who were menstruating compared with females who were not menstruating [7].

COMPONENTS OF THERAPY

Sequence of therapy — After a decision has been made to treat with fibrinolytic therapy rather than primary percutaneous coronary intervention (PCI), we use the following approach:

●Establish intravenous access and continuous electrocardiogram (ECG) monitoring.

●Administer aspirin and clopidogrel. (See 'Antiplatelet therapy' below.)

●Start parenteral anticoagulation with unfractionated heparin or enoxaparin (algorithm 2). (See 'Anticoagulant therapy' below.)

●After administration of an anticoagulant, the agent chosen for fibrinolysis is administered (table 2). The fibrinolytic agent should be administered as soon as possible. (See 'Choice of fibrinolytic agent and dosing' below and 'Quality goals' below.)

●Angiography and appropriate PCI should occur within 6 to 24 hours after fibrinolysis regardless of the initial response to fibrinolysis. Transfer to a PCI-capable hospital should be arranged accordingly. Patients who cannot undergo angiography should undergo a noninvasive test for obstructive coronary artery disease (CAD) prior to discharge. (See 'Role of angiography and stress testing' below.)

●Additional therapies for STEMI (eg, beta blocker, statin) should be initiated as appropriate. (See 'Statins' below and 'Beta blocker' below.)

Anticoagulant therapy — We treat all patients with STEMI receiving fibrinolytic therapy with an anticoagulant and should be started as soon as a decision to treat with fibrinolytic therapy is made (algorithm 2). A detailed discussion of anticoagulant therapy in STEMI patients who receive fibrinolytic therapy, including dosing regimens, can be found separately. (See "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Fibrinolytic therapy with or without planned PCI'.)

Antiplatelet therapy — We give nonenteric-coated aspirin (loading dose of 162 to 325 mg) as soon as possible after the diagnosis has been made.

Once fibrinolysis is chosen as the reperfusion strategy, we give clopidogrel as a 300 mg loading dose in those ≤75 years of age and a 75 mg loading dose in those >75 years. Transition to a more potent P2Y₁₂ inhibitor may be appropriate at the time of discharge. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Fibrinolytic therapy'.)

Choice of fibrinolytic agent and dosing — In patients with STEMI who will undergo fibrinolysis, we suggest tenecteplase or reteplase rather than alteplase based on their ease-of-use relative to alteplase, which requires a bolus followed by two separate weight-based infusions. Streptokinase use should be avoided, and streptokinase is no longer available in the United States and Canada.

The doses of fibrinolytic agents for use in patients with STEMI are described in a table (table 2).

Professional guidelines do not specify a specific agent for use [8,9].

Tenecteplase has favorable efficacy and safety relative to alteplase (ie, a lower rate of noncerebral bleeding) and only requires a single bolus to administer. However, tenecteplase requires an accurate weight for dosing, which can lead to overdosing in emergency situations. In a trial that included 16,949 patients with STEMI who underwent fibrinolysis, there was a similar rate of 30-day mortality between patients assigned to tenecteplase and alteplase (6.2 percent) [10].

Reteplase has efficacy that is similar to alteplase (30-day mortality 7.2 versus 7.5 percent; odds ratio 1.03, 95% CI 0.91-1.18) but is easier to use (ie, two intravenous boluses 30 minutes apart) [11,12].

An older trial found a lower 30-day mortality rate with alteplase compared with streptokinase (6.3 versus 7.2 percent; risk ratio 0.86, 95% CI 0.79-0.94), which led to the widespread adoption of alteplase and other fibrin-specific agents (eg, tenecteplase, reteplase) [13].

Beta blocker — Similar to other patients with MI, a beta blocker is typically a component of the therapeutic regimen and is initiated within 24 hours of diagnosis in appropriately selected patients, as discussed separately. (See "Acute myocardial infarction: Role of beta blocker therapy".)

Statins — For all patients with an acute coronary syndrome not on treatment with a statin, we initiate high-intensity statin therapy (80 mg of atorvastatin or 20 to 40 mg of rosuvastatin daily) regardless of the baseline low-density lipoprotein-cholesterol level. We start therapy as soon as possible after the diagnosis. (See "Low-density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome", section on 'Our approach to in-hospital therapy'.)

QUALITY GOALS — 

The time from first medical contact, whether it be in an ambulance capable of delivering fibrinolytic therapy or a hospital emergency department, to drug administration (ie, door-to-needle time) should be less than 30 minutes. Ideally, fibrinolytic therapy should be delivered within 10 minutes of STEMI confirmation on the ECG. This quality goal is based on studies that suggest that lower times to reperfusion are associated with improved outcomes, as described separately [14]. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Longer delay to PCI (>120-minute delay)'.)

Administration of fibrinolytic therapy before hospital arrival (eg, in an ambulance) is an established practice in some regions. The rationale, training, treatment protocols, and quality assurance programs needed to ensure a safe and effective prehospital fibrinolysis program are presented separately. (See "Acute ST-elevation myocardial infarction: Prehospital fibrinolysis".)

ROLE OF ANGIOGRAPHY AND STRESS TESTING

Routine angiography for most patients — For most patients with STEMI who undergo fibrinolysis as the primary method of reperfusion and regardless of the apparent success of fibrinolysis, routine angiography should follow fibrinolysis. The timing of angiography and other issues surrounding angiography after fibrinolysis are discussed separately (algorithm 1). (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Longer delay to PCI (>120-minute delay)'.)

Unsuccessful fibrinolysis or threatened reocclusion — Patients with evidence (eg, persistent symptoms, no change in ST-segment elevation) of unsuccessful reperfusion (ie, failed fibrinolysis) or in whom there was initial suggestion of successful reperfusion followed by worsening signs or symptoms of ischemia (ie, threatened reocclusion) typically require urgent management with angiography and appropriate percutaneous coronary intervention (PCI). The diagnosis and management of these conditions are discussed separately. (See "Acute ST elevation myocardial infarction: Failed fibrinolysis".)

Successful fibrinolysis without angiography — For patients who did not undergo angiography or PCI after fibrinolysis (eg, management with observation after fibrinolysis rather than empiric angiography), we recommend a stress test or anatomic imaging (eg, coronary computed tomographic angiography) to evaluate for obstructive CAD. In patients who have evidence of obstructive CAD, we recommend revascularization rather than no revascularization. It is reasonable to perform the assessment for ischemia prior to discharge and to arrange any revascularization within days to weeks after discharge.

This approach is consistent with professional guidelines [15-18].

Trials suggest that revascularization in patients with recurrent or residual ischemia reduces the risk of recurrent MI and likely the risk of mortality:

●In the SWISSI II trial, 201 asymptomatic patients with STEMI or non-ST-elevation MI and inducible myocardial ischemia were randomly assigned to either PCI or intensive antiischemic drug therapy [19]. During a mean follow-up of 10.2 years, patients assigned to PCI had a lower risk of mortality (3 versus 21 percent; hazard ratio [HR] 0.14, 95% CI 0.04-0.45) and recurrent MI (11 versus 40 events per 938 patient-years; HR 0.26, 95% CI 0.13-0.51).

●The DANAMI trial consisted of 1008 patients with acute STEMI who were treated with a fibrinolytic agent and developed either spontaneous symptomatic angina or inducible ischemia on a predischarge exercise ECG test. These patients were randomly assigned to conservative therapy or revascularization with PCI or coronary artery bypass graft surgery 2 to 10 weeks after the MI [20]. In the group assigned to revascularization, there was a lower rate of recurrent MI (5.6 versus 10.5 percent; relative risk [RR] 0.53, 95% CI 0.34-0.82) and admission for unstable angina (17.9 versus 29.5 percent; RR 0.61, 95% CI 0.48-0.76), while the rate of mortality was similar (3.6 versus 4.4 percent; RR 0.82, 95% CI 0.45-1.51) (figure 1).

COMPLICATIONS

Bleeding — In the largest trial of fibrinolytic therapy (eg, streptokinase or alteplase), the rate of severe bleeding with fibrinolysis was 1.8 percent [21]. The incidence of moderate bleeding, defined by the need for transfusion but without hemodynamic compromise or need for an intervention, was 11.4 percent. Bleeding was most often related to a procedure, occurring with coronary artery bypass graft surgery in 3.6 percent and at the femoral arterial access site for percutaneous coronary intervention in 2 percent. As the use of the radial artery for access has increased, the risk of significant procedure-related bleeding has decreased. (See "Primary percutaneous coronary intervention in acute ST-elevation myocardial infarction: Periprocedural management", section on 'Radial versus femoral approach'.)

The most common site for spontaneous bleeding is the gastrointestinal tract (1.8 percent) [21].

Stroke — The risks of stroke and intracranial hemorrhage (ICH) were 1.2 and 0.7 percent in a study of 12,739 patients [22]. In GUSTO-I, the majority of strokes (95 percent) occurred within five days of therapy [1,23].

Strokes associated with fibrinolysis are associated with very high rates of mortality and morbidity. Among patients enrolled in a trial who had a stroke, it was fatal in 41 percent and produced moderate or severe disability in 31 percent [1]. Similar findings were noted in the United States National Registry of Myocardial Infarction 2 [24].

Risk factors for stroke have been identified from patients enrolled in randomized trials [1,2,22,24,25]. In GUSTO-I, patients with a previous transient ischemic attack or stroke were at particularly high risk (5.5 and 6.9 percent, respectively) [1].

Independent predictors of ICH included the following:

●Age ≥75 years

●Female sex

●Prior history of stroke

●Systolic blood pressure ≥160 mmHg

●Weight ≤65 kg for females or ≤80 kg for males

●International normalized ratio >4 or prothrombin time >24 seconds

●Use of alteplase versus other fibrinolytic agents

ICH should be suspected in any patient who develops sudden neurologic deterioration, a decline in level of consciousness, new headache, nausea and vomiting, or a sudden rise in blood pressure after fibrinolytic therapy, especially within the first 24 hours of treatment. The management of such patients is similar to that for patients with other causes of ICH. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis" and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use", section on 'Management of symptomatic intracerebral hemorrhage'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: ST-elevation myocardial infarction (STEMI)".)

SUMMARY AND RECOMMENDATIONS

●Indications – Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for most patients with acute ST-elevation myocardial infarction (STEMI) (algorithm 1). When timely primary PCI is not available, immediate fibrinolysis is indicated. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy".)

●Contraindications – The absolute and relative contraindications to fibrinolytic therapy are presented in a table (table 1) and above. (See 'Absolute contraindications' above and 'Relative contraindications' above.)

●Components of therapy

•Sequence of therapy – The sequence of therapy required to provide safe and timely fibrinolysis is described above. (See 'Sequence of therapy' above.)

•Choice of agent – In patients with STEMI who will undergo fibrinolysis, we suggest tenecteplase or reteplase rather than alteplase based on their ease-of-use relative to alteplase (Grade 2C). Streptokinase use should be avoided, and streptokinase is no longer available in the United States and Canada. (See 'Choice of fibrinolytic agent and dosing' above.)

•Dosing – The dosing of fibrinolytic agents for use in STEMI are provided in tabular form (table 2).

•Anticoagulant therapy – We treat STEMI patients receiving fibrinolytic therapy with an anticoagulant. It should be started as soon as a decision to treat with fibrinolytic therapy is made. We choose either unfractionated heparin or enoxaparin for patients, including those who may receive PCI after fibrinolysis (algorithm 2). A detailed discussion of anticoagulant therapy in patients with STEMI who receive fibrinolytic therapy, including the dosing regimens, can be found separately. (See "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Fibrinolytic therapy with or without planned PCI'.)

•Antiplatelet therapy – We give nonenteric-coated aspirin (loading dose of 162 to 325 mg) as soon as possible after the diagnosis has been made.

Once fibrinolysis is chosen as the reperfusion strategy, we give clopidogrel as a 300 mg loading dose in those ≤75 years old and a 75 mg loading dose in those >75 years old. Transition to a more potent P2Y₁₂ inhibitor may be appropriate at the time of discharge. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Fibrinolytic therapy'.)

•Statin – For all patients with an acute coronary syndrome not on treatment with a statin, we initiate high-intensity statin therapy (80 mg of atorvastatin or 20 to 40 mg of rosuvastatin daily) regardless of the baseline low-density lipoprotein-cholesterol level. We start therapy as soon as possible after the diagnosis. (See "Low-density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome", section on 'Our approach to in-hospital therapy'.)

•Beta blocker – Similar to other patients with MI, a beta blocker is typically a component of the therapeutic regimen and is initiated within 24 hours of diagnosis in appropriately selected patients. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Fibrinolytic therapy'.)

•Quality goals – Regardless of whether fibrinolytic therapy is given prehospital or in the hospital (emergency department), it should be started within 30 minutes after the diagnosis of STEMI is made. (See 'Quality goals' above.)

●Complications – The major complications of fibrinolysis are stroke, cerebral hemorrhage, and noncerebral bleeding. (See 'Complications' above.)

●Role of angiography and stress testing

•Routine angiography for most patients – For most patients with STEMI who undergo fibrinolysis as the primary method of reperfusion and regardless of the apparent success of fibrinolysis, routine angiography should follow fibrinolysis (algorithm 1). The timing of angiography and other issues surrounding angiography after fibrinolysis are discussed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Longer delay to PCI (>120-minute delay)'.)

•Unsuccessful fibrinolysis or threatened reocclusion – The management of patients with evidence (eg, persistent symptoms, no change in ST-segment elevation) of unsuccessful reperfusion after fibrinolysis (ie, failed fibrinolysis) or threatened reocclusion after initially successful fibrinolysis is discussed separately. (See "Acute ST elevation myocardial infarction: Failed fibrinolysis".)

•Successful fibrinolysis without angiography – For patients who did not undergo angiography after fibrinolysis (eg, management with observation after fibrinolysis rather than empiric angiography), we recommend a stress test or anatomic imaging (eg, coronary computed tomographic angiography) to evaluate for obstructive coronary artery disease (CAD) rather than no such testing. In patients who have evidence of obstructive CAD, we recommend revascularization rather than no revascularization (Grade 1B). It is reasonable to perform the assessment for ischemia prior to discharge and to arrange any revascularization within days to weeks after discharge. (See 'Successful fibrinolysis without angiography' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Thomas Levin, MD, who contributed to previous versions of this topic review.

We are saddened by the death of Ramon Corbalan, MD, who passed away in November 2023. UpToDate acknowledges Dr. Corbalan's past work as an author for this topic.