title: Streptokinase. A review of its pharmacology and therapeutic efficacy in acute myocardial infarction in older patients.
abstract: Streptokinase has been administered to many thousands of elderly patients with acute myocardial infarction. Results of large, randomised trials provide convincing evidence that intravenous streptokinase confers a distinct survival benefit in this population subgroup following myocardial infarction. The placebo-controlled ISIS-2 study demonstrated a 5-week absolute mortality reduction of 38 per 1000 patients aged 60 to 69 years administered streptokinase, compared with only 16 per 1000 for patients aged less than 60 years. Combining streptokinase with aspirin further reduces mortality, as shown by a 5-week absolute mortality reduction of 70 per 1000 patients aged 60 to 69 years administered this regimen in the ISIS-2 trial. While ideally patients should receive streptokinase as soon as possible after symptom onset, late benefit has been observed in patients presenting up to 12 hours after pain onset, as is often the case with the elderly. Indeed, in patients treated > 6 hours after infarct in the GUSTO trial, streptokinase produced lower mortality results than accelerated recombinant tissue plasminogen activator (rt-PA). However, in contrast to the similar effects of streptokinase and conventionally administered rt-PA on overall survival demonstrated in previous large trials, the GUSTO study showed a lower mortality rate for accelerated rt-PA than for streptokinase in the elderly and in the total patient population. The most frequent adverse effects associated with streptokinase therapy are haemorrhagic complications, with an incidence of 0.4% for major bleeding (requiring transfusion) and 3.6% for minor bleeding among the total population in the GISSI-1 and ISIS-2 trials. An excess of stroke, particularly haemorrhagic stroke, occurring with rt-PA in GUSTO and other major mortality trials affirms the use of streptokinase as a suitable option in the elderly who are at increased risk of this complication. Significantly reduced values of end-systolic volume and regional wall motion index have been observed in elderly patients following streptokinase therapy. Overall, streptokinase and rt-PA seem to cause similar improvements in left ventricular function in this age group. Patency of occluded coronary arteries appears to be achieved in a high percentage of elderly patients following streptokinase therapy, based on a small sample. Thus, in view of the extensive clinical experience that now exists, intravenous streptokinase represents an appropriate alternative in elderly patients with acute myocardial infarction, and may be considered a first-line therapy in selected individuals, such as those with multiple risk factors for stroke or who present later than 6 hours after infarct.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Adis International Limited, Auckland, New Zealand.
authors.forename: P E
authors.initials: PE
authors.lastname: Battershill
authors.forename: P
authors.initials: P
authors.lastname: Benfield
authors.forename: K L
authors.initials: KL
authors.lastname: Goa
mesh_terms: D000375:Aging / Q000187:drug effects*; D001777:Blood Coagulation / Q000187:drug effects; D002986:Clinical Trials as Topic; D005342:Fibrinolysis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D013300:Streptokinase / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D013300:Streptokinase