What clinical trials have been done on streptokinase (Streptokinase) in patients with ST-Elevation Myocardial Infarction (STEMI)?

From the Guidelines

Streptokinase has been studied in several clinical trials for the treatment of ST-Elevation Myocardial Infarction (STEMI), with results showing that primary PCI is generally superior to fibrinolysis with streptokinase.

Key Findings

• The PRAGUE study, a multicenter, randomized controlled trial, found that primary PCI had a lower rate of death, myocardial infarction, or stroke at 30 days compared to streptokinase during transfer for facilitated PCI and streptokinase without transfer 1.
• The PRAGUE-2 study, a larger nationwide trial, also found that primary PCI had a lower 30-day mortality rate compared to streptokinase, particularly in patients who presented more than 3 hours after the onset of chest pain 1.
• A meta-analysis of six randomized trials found that transfer for primary PCI reduced the combined end point of death, reinfarction, or stroke by 42% compared to on-site thrombolysis 1.

Clinical Trials

• The DANAMI-2 trial, a Danish national, multicenter, randomized controlled trial, compared primary PCI with fibrinolysis for the treatment of STEMI and found a statistically significant reduction in the primary end point of death, reinfarction, and stroke at 30 days for patients treated with primary PCI 1.
• The Air Primary Angioplasty in Myocardial Infarction (Air-PAMI) study, a small, multicenter randomized study, compared fibrinolysis with transfer for primary PCI and found a trend toward fewer major adverse cardiac events in the primary PCI group at 30 days 1.

Treatment Recommendations

• The ACCF/AHA guideline for the management of STEMI recommends that patients who present with STEMI to a non-PCI-capable hospital should receive timely fibrinolytic therapy, if interhospital timely transfer time for primary PCI is not feasible 1.
• The guideline also sets a benchmark time goal from hospital arrival to drug administration, or DTN time, to be ≤30 min 1.
• The use of streptokinase is generally not recommended as a first-line treatment for STEMI, due to the availability of more effective and safer alternatives, such as primary PCI and other fibrinolytic agents 1.

From the FDA Drug Label

The comparative efficacy of these two regimens has not been evaluated. Accelerated Infusion in AMI Patients Accelerated infusion of Activase was studied in an international, multi-center trial that randomized 41,021 patients with AMI to four thrombolytic regimens (Study 3). Entry criteria included onset of chest pain within 6 hours of treatment and ST-segment elevation of ECG The four treatment regimens included accelerated infusion of Activase (≤100 mg over 90 minutes) plus intravenous (IV) heparin (n = 10,396); Streptokinase (1. 5 million units over 60 minutes) plus IV heparin (SK [IV], n =10,410); Streptokinase plus subcutaneous (SQ) heparin (SK [SQ] n= 9841).

Key results from Study 3 are shown in Table 8. The incidence of 30-day mortality for Activase accelerated infusion was 1. 0% lower than for either Streptokinase plus heparin regimen. The incidence of combined 30-day mortality or nonfatal stroke for the Activase accelerated infusion was 1.0% lower than for SK (IV) and 0. 8% lower than for SK (SQ).

The clinical trials done on Streptokinase in patients with ST-Elevation Myocardial Infarction (STEMI) include:

• Study 3: an international, multi-center trial that randomized 41,021 patients with AMI to four thrombolytic regimens, including Streptokinase (1.5 million units over 60 minutes) plus IV heparin (SK [IV], n =10,410) and Streptokinase plus subcutaneous (SQ) heparin (SK [SQ] n= 9841) 2. Key findings:
• The incidence of 30-day mortality for Streptokinase plus heparin regimen was higher than for Activase accelerated infusion.
• The incidence of combined 30-day mortality or nonfatal stroke for the Streptokinase plus heparin regimen was higher than for Activase accelerated infusion.

From the Research

Clinical Trials on Streptokinase in STEMI Patients

• The GISSI-1 and ISIS-2 trials, as mentioned in 3, demonstrated the effectiveness of streptokinase in reducing mortality in STEMI patients.
• A review of randomized trials on intracoronary and intravenous streptokinase therapy, as discussed in 4, showed that streptokinase therapy reduces mortality when initiated within the first 6 hours of acute myocardial infarction.
• The ASK-ROMANIA registry, as described in 5, compared the efficacy and safety of four streptokinase regimens in STEMI patients and found that accelerated streptokinase regimens resulted in higher rates of coronary reperfusion and lower in-hospital mortality.
• A study published in 6 compared the efficacy and safety of accelerated versus standard streptokinase infusion regimens in STEMI patients and found that the accelerated regimen was safe and effective, with a higher rate of successful reperfusion.
• A study conducted at the Karachi Institute of Heart Diseases, as reported in 7, found that the magnitude of ST-segment resolution after thrombolytic therapy with streptokinase predicts short- and long-term outcomes in patients with acute myocardial infarction.

Key Findings

• Streptokinase therapy reduces mortality in STEMI patients when initiated within the first 6 hours of acute myocardial infarction 4.
• Accelerated streptokinase regimens result in higher rates of coronary reperfusion and lower in-hospital mortality 5, 6.
• The magnitude of ST-segment resolution after thrombolytic therapy with streptokinase predicts short- and long-term outcomes in patients with acute myocardial infarction 7.

Study Characteristics

• The GISSI-1 and ISIS-2 trials were among the first to demonstrate the effectiveness of streptokinase in STEMI patients 3.
• The ASK-ROMANIA registry was a multicenter registry that compared the efficacy and safety of four streptokinase regimens in STEMI patients 5.
• The study published in 6 was a randomized trial that compared the efficacy and safety of accelerated versus standard streptokinase infusion regimens in STEMI patients.
• The study conducted at the Karachi Institute of Heart Diseases was a quasi-experimental study that evaluated the efficacy of reperfusion therapy with streptokinase in STEMI patients 7.