Version July 2025
INTRODUCTION —
Coronary reperfusion with fibrinolysis or primary percutaneous coronary intervention (PCI) improves survival in patients with acute ST-elevation myocardial infarction (STEMI) compared with no reperfusion therapy. While PCI is preferred for most patients if it can be performed by an experienced operator with less than a 120-minute delay from first medical contact, fibrinolysis remains an important therapeutic modality, due in part to limited availability of primary PCI in some locations (algorithm 1). (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Approach in most patients'.)
This topic will review the diagnosis and management of primary failure of fibrinolysis and threatened reocclusion.
The roles of routine angiography, PCI, and fibrinolysis in the management of STEMI are discussed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy" and "Acute ST-elevation myocardial infarction: Management of fibrinolysis".)
PRIMARY FAILURE OF FIBRINOLYSIS
Incidence and prognosis — Failed fibrinolysis, defined as Thrombolysis in Myocardial Infarction (TIMI) grade (table 1) 0 to 2 flow, occurs in 40 to 45 percent of patients within 60 to 90 minutes of administration of a fibrinolytic agent [1,2].
TIMI 3 (normal) flow is associated with both short- and long-term mortality benefit after fibrinolysis (figure 1 and figure 2) [2-7]. As an example, a meta-analysis of five trials of almost 4000 patients found that short-term mortality (≤30 days) was 3.7, 7, and 8.8 percent among patients with TIMI grade 3, 2, and 0 to 1, respectively [2].
When to suspect failure of fibrinolysis — Failure of fibrinolysis should be suspected if the following are present at least 60 minutes after administration of fibrinolytic therapy [8]:
●Persistent or worsening chest discomfort
●Absence of at least 50 percent improvement in ST-segment elevation [9-11]
●New or worsening hemodynamic stability or heart failure
The diagnosis is confirmed if coronary angiography demonstrates a coronary artery lesion with abnormal blood flow.
While persistent ST-segment elevation suggests failed fibrinolysis, its absence or presence does not correlate well with angiographic findings. In the TIMI 14 trial of 444 patients who underwent angiography at 90 minutes after fibrinolytic therapy [12,13], TIMI 3 flow was present in 79 percent of patients with complete ST-segment resolution and in approximately 50 percent of patients with partial or no ST-segment resolution.
THREATENED REOCCLUSION OR REINFARCTION
Incidence and risk factors — After apparently successful fibrinolysis by either clinical or angiographic criteria, early recurrence of ischemia or infarction occurs in approximately 4 percent of patients [14-18].
There are no clear risk factors for reocclusion [14,15,19,20].
Clinical manifestations and diagnosis — In patients who had apparently successful fibrinolysis followed at least 60 minutes later by new or worsening signs of ischemia or infarction (eg, chest discomfort, heart failure), recurrent biomarker elevation of at least 50 percent, or recurrent ST-segment elevation, reocclusion or reinfarction should be suspected [10,11].
In patients who underwent fibrinolysis and have signs of recurrent ischemia, the differential diagnosis includes other complications of MI (eg, papillary muscle rupture, ventricular septal defect, tamponade). If such a complication is suspected based on clinical findings (eg, murmur, hypoxia, hypotension) echocardiography or ventriculography may help to identify such a complication. These complications of MI are discussed elsewhere. (See "Acute myocardial infarction: Mechanical complications".)
MANAGEMENT —
In patients with suspected primary failure of fibrinolysis or threatened reocclusion, we recommend angiography with appropriate percutaneous coronary intervention (PCI) rather than repeat fibrinolysis or no attempt at reperfusion. If arrangements for transfer were not made as part of routine fibrinolytic therapy, which is our preference, arrangements for emergency transfer to a PCI-capable center should be made upon suspicion of failed fibrinolysis or threatened reocclusion. In general, angiography should be performed within 120 minutes of suspected reocclusion.
If PCI is not available, it is reasonable to retreat with fibrinolytics. If repeat fibrinolysis is planned, alteplase, tenecteplase, or reteplase are reasonable options for therapy. The risk of bleeding with a second dose of a fibrinolytic agent may be reduced by waiting at least 90 minutes from the first administration of an agent to administer the second dose. Retreatment with streptokinase or anistreplase should be avoided due to the potential for development of neutralizing antibodies, which may render these agents ineffective [21,22].
Our recommendations are generally in agreement with those of professional organizations [10,11,23].
For the treatment of failed fibrinolysis and threatened reocclusion, we prefer PCI to other approaches based on indirect data from trials that suggest that primary PCI is more effective and safer (eg, lower risk of stroke) than primary fibrinolysis and that a pharmacoinvasive strategy (ie, immediate transfer for angiography and PCI after initiation of fibrinolytics) is superior to a strategy of waiting for signs of failed fibrinolysis or reocclusion. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'PCI is immediately available' and "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Longer delay to PCI (>120-minute delay)'.)
In trials that directly addressed different approaches to management of primary failure of fibrinolysis, patients with failed fibrinolysis who had PCI had a lower rate of recurrent MI. In a meta-analysis of randomized trials that included 908 patients with failed fibrinolysis, patients assigned to rescue PCI had a lower rate of recurrent MI (6 versus 11 percent in the conservative management group; relative risk [RR] 0.58, 95% CI 0.35-0.97) and nonsignificantly lower rates of mortality (7 versus 10 percent; RR 0.69, 95% CI 0.23-1.05) and heart failure (13 versus 18 percent; RR 0.73, 95% CI 0.54-1.00) [24].
Studies that directly compared treatments for reocclusion were retrospective in nature [16]; as such, we rely on trials that compared fibrinolysis with or without early angiography and PCI to guide management.
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
●Primary failure of fibrinolysis
•Incidence – Failed fibrinolysis, defined as Thrombolysis in Myocardial Infarction (TIMI) grade (table 1) 0 to 2 flow, occurs in 40 to 45 percent of patients within 60 to 90 minutes of administration of a fibrinolytic agent.
•When to suspect and diagnosis – Failure of fibrinolysis should be suspected if the following are present at least 60 minutes after administration of fibrinolytic therapy:
-Persistent or worsening chest discomfort
-Absence of at least 50 percent improvement in ST-segment elevation
-New or worsening hemodynamic stability or heart failure
The diagnosis is confirmed if coronary angiography demonstrates a coronary artery lesion with abnormal blood flow. (See 'When to suspect failure of fibrinolysis' above.)
●Threatened reocclusion or reinfarction
•Incidence – After apparently successful fibrinolysis by either clinical or angiographic criteria, early recurrence of ischemia or infarction occurs in approximately 4 percent of patients. (See 'Incidence and risk factors' above.)
•Diagnosis – In patients who had apparently successful fibrinolysis followed at least 60 minutes later by new or worsening signs of ischemia or infarction (eg, chest discomfort, heart failure), recurrent biomarker elevation of at least 50 percent, or recurrent ST-segment elevation, reocclusion or reinfarction should be suspected. (See 'Clinical manifestations and diagnosis' above.)
●Management – In patients with suspected primary failure of fibrinolysis or threatened reocclusion, we recommend angiography with appropriate percutaneous coronary intervention (PCI) rather than repeat fibrinolysis or no attempt at reperfusion (Grade 1B). If arrangements for transfer were not made as part of routine fibrinolytic therapy, which is our preference, arrangements for emergency transfer to a PCI-capable center should be made upon suspicion of failed fibrinolysis or reocclusion. In general, angiography should be performed within 120 minutes of suspected failure or reocclusion.
If PCI is not available, it is reasonable to retreat with fibrinolytics. If repeat fibrinolysis is planned, alteplase, tenecteplase, or reteplase are reasonable options for therapy. The risk of bleeding with a second dose of a fibrinolytic agent may be reduced by waiting at least 90 minutes from the first fibrinolytic administration to administer the second dose. Retreatment with streptokinase or anistreplase should be avoided due to the potential for development of neutralizing antibodies, which may render these agents ineffective. (See 'Management' above.)
