Anistreplase (Eminase)

Anistreplase is a real, FDA-approved thrombolytic — a chemically modified streptokinase-plasminogen complex approved in 1989 on the strength of a trial showing roughly a 50% reduction in 30-day mortality against placebo — that let doctors give a single few-minute bolus instead of streptokinase's hour-long infusion, only to be displaced within the decade once bolus-dosed tPA-class drugs offered the same convenience without streptokinase's antigenicity, and it is no longer marketed in the US.

A chemically blocked streptokinase complex, built for a single bolus

Anistreplase, also called APSAC (anisoylated plasminogen-streptokinase activator complex), is not a distinct molecule discovered on its own but a chemically engineered version of streptokinase itself: streptokinase is pre-combined with human plasminogen, and the resulting complex's active site is temporarily blocked with an anisoyl (p-anisoyl) group. That acyl group slowly hydrolyzes off once injected, releasing active plasminogen-activator complex gradually into the bloodstream — extending its effective working half-life enough to allow a single intravenous bolus given over about 2 to 5 minutes, instead of streptokinase's roughly hour-long infusion. It was developed by Beecham (later SmithKline Beecham, now part of GSK) and marketed in the US as Eminase, the third thrombolytic to reach the US market after streptokinase and alteplase.

The AIMS trial: roughly halving 30-day mortality against placebo

The FDA approved anistreplase (as Eminase) on 27 November 1989, following a roughly 16-month review, based primarily on the AIMS trial (APSAC Intervention Mortality Study, AIMS Trial Study Group, "Effect of Intravenous APSAC on Mortality After Acute Myocardial Infarction: Preliminary Report of a Placebo-Controlled Clinical Trial," Lancet 1988;1(8585):545-549): 1,258 patients randomized to anistreplase or placebo within 6 hours of symptom onset found 30-day mortality of 6.5% with anistreplase versus 17.8% with placebo, an odds reduction of roughly 50% (p=0.0006) — one of the largest placebo-controlled mortality effects reported for any thrombolytic. A later report on the same cohort found the mortality benefit persisted well beyond 30 days, with most of the separation between groups established in that initial month.

ISIS-3: statistically equivalent to streptokinase and tPA, with a non-significant excess of strokes

The largest head-to-head comparison came three years later in 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 randomized patients among all three thrombolytics covered in this cluster. Anistreplase's 35-day mortality (10.5%) was statistically indistinguishable from streptokinase's (10.6%) and tPA's (10.3%). Stroke rates were slightly higher with anistreplase than with streptokinase (1.26% vs. 1.04%), including more hemorrhagic strokes (0.55% vs. 0.24%), but the overall stroke-rate difference did not reach statistical significance (p=0.08) — a real signal, but one the trial could not confirm as a true excess risk rather than chance.

Current status

Anistreplase is listed as previously marketed in the US and is no longer commercially available; SmithKline Beecham's once-touted single-bolus convenience stopped being a unique advantage once tenecteplase and reteplase — the bolus-dosed tPA-class drugs covered elsewhere on this site — reached the market offering similar ease of administration without streptokinase's antigenicity and antibody-formation risk. Reported clinical interest and trial enrollment for anistreplase-based studies had already softened by the early-to-mid 1990s as those alternatives emerged. It carries no wellness, cosmetic, or self-administered use of any kind — it was, like the other thrombolytics on this site, a hospital-only emergency drug given under direct clinical supervision.