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Streptase, Streptokinase, acts with plasminogen to produce an "activator complex" that converts plasminogen to the proteolytic enzyme plasmin. The t Â½ of the activator complex is about 23 minutes; the complex is inactivated, in part, by antistreptococcal antibodies. The mechanism by which dissociated streptokinase is eliminated is clearance by sites in the liver; however, no metabolites of streptokinase have been identified. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. Plasmin is inactivated by circulating inhibitors, such as (alpha)-2-plasmin inhibitor or (alpha)-2-macroglobulin. These inhibitors are rapidly consumed at high doses of streptokinase.
Intravenous infusion of Streptokinase is followed by increased fibrinolytic activity, which decreases plasma fibrinogen levels for 24 to 36 hours. The decrease in plasma fibrinogen is associated with decreases in plasma and blood viscosity and red blood cell aggregation. The hyperfibrinolytic effect disappears within a few hours after discontinuation, but a prolonged thrombin time may persist for up to 24 hours due to the decrease in plasma levels of fibrinogen and an increase in the amount of circulating fibrin(ogen) degradation products (FDP). Depending upon the dosage and duration of infusion of Streptokinase, the thrombin time will decrease to less than two times the normal control value within 4 hours, and return to normal by 24 hours.
Intravenous administration has been shown to reduce blood pressure and total peripheral resistance with a corresponding reduction in cardiac afterload. These expected responses were not studied with the intracoronary administration of Streptase, Streptokinase. The quantitative benefit has not been evaluated.
Variable amounts of circulating antistreptokinase antibody are present in individuals as a result of recent streptococcal infections. The recommended dosage schedule usually obviates the need for antibody titration.
Two very large, randomized, placebo-controlled studies (1,2) involving almost 30,000 patients have demonstrated that a 60-minute intravenous infusion of 1,500,000 IU of Streptokinase significantly reduces mortality following a myocardial infarction. One of these studies also evaluated concomitant oral administration of low dose aspirin (160 mg/d over one month).
In the GISSI study the reduction in mortality was time dependent. There was a 47% reduction in mortality among patients treated within one hour of the onset of chest pain, a 23% reduction among patients treated within three hours, and a 17% reduction among patients treated between three and six hours. There was also a reduction in mortality in patients treated between six and twelve hours from the onset of symptoms, but the reduction was not statistically significant.
In the ISIS-2 study the reduction in mortality was also time dependent. If Streptokinase and aspirin were administered within the first hour after symptom onset, the reduction in mortality was 44%. The reduction in the odds of death in patients treated within four hours was 53% for the combination of Streptokinase and aspirin, and 35% for Streptokinase alone. However, the reduction was still significant when treatment was started 5-24 hours after symptom onset: 33% for the combined therapy and 17% for Streptokinase alone. Overall, in the 0-24 hour time period there was a 42% reduction in the odds of death with combined treatment (Streptokinase and aspirin) versus placebo (2p<0.00001) and a 25% reduction in the odds of death with Streptokinase alone versus placebo (2p<0.00001).
One of eight smaller studies using a similar dosing schedule showed a statistically significant reduction in mortality. When all of these studies were pooled, the overall decrease in mortality was approximately 23%. Results from pooling several studies using different dosages with long term infusion corroborate these observations.
In addition, studies measuring left ventricular ejection fraction (LVEF) at discharge showed the mean LVEFs were 3-6 percentage points higher in the Streptokinase group than in the control group. This difference was statistically significant in some of the studies (3,4) . Furthermore, some studies reported greater improvement in LVEF among patients treated within three hours than in patients treated later.
Results from a randomized controlled trial in over 11,000 patients show that, following treatment with IV Streptokinase, there is a reduction in the number of patients with clinical congestive heart failure during the 14-21 day in-hospital period. Clinical congestive heart failure occurred in 12.8% of Streptokinase-treated patients compared with 15% of the control patients (p=0.001) (1) .
The rate of reocclusion of the infarct-related vessel has been reported to be approximately 15-20%. The rate of reocclusion depends on dosage, additional anticoagulant therapy and residual stenosis. When the reinfarctions were evaluated in studies involving 8800 Streptokinase-treated patients, the overall rate was 3.8% (range 2-15%). In over 8500 control patients, the rate of reinfarction was 2.4%. However, the ISIS-2 study showed that an increase in reinfarction was avoided when Streptokinase was combined with low dose aspirin. The rate of reinfarction in the combination group was 1.8% vs. 1.9% in the group given aspirin alone.
Streptase, Streptokinase, administered by the intracoronary route has resulted in thrombolysis usually within one hour, and ensuing reperfusion results in improvement of cardiac function and reduction of mortality (5,6) . LVEF was increased in patients treated with Streptokinase when compared to patients treated with conventional therapy. When the initial LVEF was low, the Streptokinase-treated patients showed greater improvement than did the controls. Spontaneous reperfusion is known to occur and has been observed with angiography at various time points after infarction. Data from one study show that 73% of Streptokinase-treated patients and 47% of the placebo-allocated patients reperfused during hospitalization. The relationship between coronary artery patency and clinical efficacy has not been established.
Studies with thrombolytic therapy for pulmonary embolism show no significant difference in lung perfusion scan between the thrombolysis group and the heparin group at one-year follow-up. However, measurements of pulmonary capillary blood volumes and diffusing capacities at two weeks and one year after therapy indicate that a more complete resolution of thrombotic obstruction and normalization of pulmonary physiology was achieved with thrombolytic therapy, thus preventing the long term sequelae of pulmonary hypertension and pulmonary failure (7) .
The long term benefit of Streptase, Streptokinase, therapy for deep vein thrombosis (DVT) has been evaluated venographically (8) . The combined results of five randomized studies show no residual thrombotic material in 60-75% of patients treated with Streptokinase versus only 10% of those treated with heparin. Thrombolytic therapy also preserves venous valve function in a majority of cases, thus avoiding the pathologic venous changes that produce the clinical post-phlebitic syndrome which occurs in 90% of the DVT patients treated with heparin.
There is a time-related decrease in effectiveness when Streptase, Streptokinase, is used in the management of peripheral arterial thromboembolism. When administered three to ten days after onset of obstruction, rates of clearance of 50-75% were reported.
Last reviewed on RxList: 10/7/2008
This monograph has been modified to include the generic and brand name in many instances.
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