STREPTOKINASE - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC EFFICACYIN ACUTE MYOCARDIAL-INFARCTION IN OLDER PATIENTS

Streptokinase has been administered to many thousand of elderly patien ts with acute myocardial infarction. Results of large, randomised tria ls provide convincing evidence that intravenous streptokinase confers a distinct survival benefit in this population subgroup following myoc ardial 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 f or patients aged less than 60 years. Combining streptokinase with aspi rin further reduces mortality, as shown by a 5-week absolute mortality reduction of 70 per 1000 patients aged 60 to 69 years administered th is regimen in the ISIS-2 trial. While ideally patients should receive streptokinase as soon as possible after symptom onset, late benefit ha s been observed in patients presenting up to 12 hours afterpain 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 act ivator (rt-PA). However in contrast to the similar effects of streptok inase and conventionally administered rt-PA on overall survival demons trated in previous large trials, the GUSTO study showed a lower mortal ity rate for accelerated rt-PA than for streptokinase in the elderly a nd 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) a nd 3.6% for minor bleeding among the total population in the GISSI-1 a nd ISIS-2 trials. An excess of stroke, particularly haemorrhagic strok e, occurring with rt-PA in GUSTO and other major mortality trials affi rms the use of streptokinase as a suitable option in the elderly who a re at increased risk of this complication. Significantly reduced value s of end-systolic volume and regional wall motion index have been obse rved in elderly patients following streptokinase therapy. Overall, str eptokinase and rt-PA seem to cause similar improvements in left ventri cular function in this age group. Patency of occluded coronary arterie s appears to be achieved in a high percentage of elderly patients foll owing streptokinase therapy, based on a small sample. Thus, in view of the extensive clinical experience that now exists, intravenous strept okinase represents an appropriate alternative in elderly patients with acute myocardial infarction, and may be considered a first-line thera py in selected individuals, such as those with multiple risk factors f or stroke or who present later than 6 hours after infarct. Furthermore , age alone should not be considered a contraindication to the use of streptokinase, as current evidence convincingly shows an increased pat ient survival with an acceptable risk of haemorrhagic complications in the elderly.