Streptokinase (Streptase)

Streptokinase is a real, FDA-approved bacterial-protein thrombolytic — the drug that opened the entire clot-buster era, with two landmark trials in the 1980s proving it cut heart-attack deaths — but it is a foreign bacterial protein rather than a copy of a human enzyme, and it is no longer commercially available in either the US or Canada, having lost out to the tPA-class drugs (alteplase, reteplase, tenecteplase) covered elsewhere on this site.

A bacterial protein, not a copy of a human enzyme

Streptokinase is a protein purified from cultures of group C beta-hemolytic streptococcal bacteria (Streptococcus equisimilis), first identified by William Tillett in 1933 as a substance that could dissolve blood clots. Unlike alteplase, reteplase and tenecteplase — recombinant copies or variants of the human enzyme tissue plasminogen activator, all covered elsewhere on this site — streptokinase is not native to the human body: it works indirectly, forming a complex with the body's own plasminogen that then activates other plasminogen molecules into the clot-dissolving enzyme plasmin. Because it is a foreign bacterial protein, the immune system can raise neutralizing antibodies against it after a single exposure, and a meaningful share of patients carry pre-existing antibodies from prior streptococcal infections — both a source of allergic reactions and a practical reason streptokinase is not normally re-administered to the same patient within roughly six months to a year of a first dose.

GISSI-1 and ISIS-2: the trials that opened the thrombolytic era

The FDA approved streptokinase (as Streptase) in 1977 for deep-vein thrombosis and pulmonary embolism, with the indication extended to acute myocardial infarction by the early-to-mid 1980s as smaller angiographic studies, including the 250-patient Western Washington intracoronary streptokinase trial (Kennedy JW, Ritchie JL, Davis KB, Fritz JK, "Western Washington Randomized Trial of Intracoronary Streptokinase in Acute Myocardial Infarction," N Engl J Med 1983;309(24):1477-1482), showed it could reopen blocked coronary arteries. Two much larger European trials then established the mortality case that made thrombolysis routine care. GISSI-1 (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico, "Effectiveness of Intravenous Thrombolytic Treatment in Acute Myocardial Infarction," Lancet 1986;1(8478):397-402, PMID 2868337), 11,712 patients, found 21-day mortality of 10.7% with streptokinase versus 13.0% on standard care alone (relative risk 0.81, p=0.0002). ISIS-2 (ISIS-2 Collaborative Group, "Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither Among 17,187 Cases of Suspected Acute Myocardial Infarction," Lancet 1988;2(8607):349-360, PMID 2903874) found streptokinase alone cut 5-week vascular mortality from 12.0% to 9.2% (a 25% odds reduction), and streptokinase combined with aspirin cut it further, to 8.0% versus 13.2% with neither — a 42% odds reduction that made aspirin-plus-thrombolytic the new default.

ISIS-3: no worse than tPA on mortality, and fewer strokes — until GUSTO-I changed the comparison

The most direct head-to-head test of streptokinase against alteplase-class thrombolytics was ISIS-3 (ISIS-3 Collaborative Group, "ISIS-3: A Randomised Comparison of Streptokinase vs Tissue Plasminogen Activator vs Anistreplase and of Aspirin Plus Heparin vs Aspirin Alone Among 41,299 Cases of Suspected Acute Myocardial Infarction," Lancet 1992;339(8796):753-770, PMID 1347801), which found essentially no difference in 35-day mortality across the three thrombolytics (10.6% streptokinase, 10.3% tPA, 10.5% anistreplase, the latter covered separately on this site) — and significantly fewer strokes with streptokinase than with tPA (1.04% vs 1.39%, p<0.01), largely driven by fewer hemorrhagic strokes (0.24% vs 0.66%). On that evidence, streptokinase looked at least as good as tPA and arguably safer. The result did not hold up: the tPA regimen ISIS-3 used (duteplase, infused over about four hours) was slower than the "accelerated," front-loaded alteplase infusion tested the following year in GUSTO-I (already covered on this site's alteplase page), which found a real 30-day mortality advantage for accelerated alteplase over streptokinase (6.3% vs 7.2-7.4%) — a result that settled the debate in the tPA class's favor and drove streptokinase's decline in US practice through the 1990s.

Current status: gone from North America, still used where cost is the deciding factor

Streptokinase (Streptase) is no longer commercially available in the United States, and Health Canada's drug product database shows its Canadian authorizations cancelled in stages — the original Hoechst-marketed formulations in 1996, and the CSL Behring-marketed formulation in 2012. Streptokinase's antigenicity, real bleeding and allergic-reaction risks, and the tPA class's demonstrated mortality edge in accelerated dosing all pushed US and Canadian hospitals toward alteplase, reteplase and tenecteplase instead. Streptokinase remains manufactured and used in other countries, where its far lower cost than any tPA-class biologic still matters for health systems without the budget for the newer drugs. It carries no wellness, cosmetic, or self-administered use of any kind — it is a hospital-only emergency drug given under direct clinical supervision.