Cardiology · 1986
GISSI-1 (Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction)
Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico, first trial
Through the first half of the 1980s, the management of acute myocardial infarction remained largely supportive. Nitrates, beta-blockers, and lidocaine prophylaxis against arrhythmias were the working tools in coronary care units, and in-hospital mortality from acute MI typically ran between 12 and 15 percent. The thrombotic basis of most acute infarctions was understood, and small trials of intracoronary streptokinase had shown angiographic evidence of recanalization, but those trials were too small to detect a mortality effect with confidence and required catheterization laboratory access that most hospitals did not have.
The Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico network assembled 176 coronary care units across Italy and enrolled patients with suspected acute MI presenting within 12 hours of symptom onset. Between 1984 and 1985, 11,806 patients were randomized to intravenous streptokinase or standard care. The design was deliberately simple: IV streptokinase required no catheterization laboratory, only a peripheral line, making it deployable at any hospital running a coronary care unit. Fausto Rovelli coordinated the multicenter network throughout the enrollment period.
The results, published in the Lancet in 1986, showed 21-day mortality of 10.7 percent in the streptokinase group versus 13.0 percent in the control group, an absolute reduction of 2.3 percentage points and a relative reduction of approximately 18 percent. Patients treated within the first hour showed a larger benefit; the effect was still present at three hours but attenuated with later treatment, and was minimal beyond six hours. The time-dependence of benefit was one of the trial's most consequential findings, translating directly into the clinical imperative of minimizing door-to-needle time.
At that scale, the trial produced a mortality finding that was unambiguous, and the absolute benefit of roughly 23 lives saved per 1,000 patients treated within three hours was large enough to shift practice without waiting for replication. ISIS-2, published two years later, confirmed the finding with streptokinase and extended it to aspirin, showing additive benefit. Together, GISSI-1 and ISIS-2 established intravenous thrombolysis as standard care for ST-elevation MI at hospitals without immediate catheterization capability, and early reperfusion time became a measurable quality indicator in coronary care.
GISSI-1 also reshaped how the cardiology community thought about conducting large, simple randomized trials. Its design, enrolling broad, unselected populations across many centers with a minimal protocol, produced an answer that previous small trials had been unable to generate. Its success influenced the design of subsequent mega-trials in cardiology. Percutaneous coronary intervention eventually superseded thrombolysis as the preferred reperfusion strategy where catheterization laboratories were available around the clock, but in hospitals and health systems without that infrastructure, pharmacological reperfusion based on the GISSI framework remains standard practice.
Key People
- Fausto Rovelli — GISSI principal investigator coordinating the Italian multicenter network
- GISSI Investigators Group — Collaborative group of 176 Italian coronary care units running the trial
- Gianni Tognoni — Mario Negri Institute statistician and co-architect of GISSI's large simple trial design
Lancet. 1986;1(8478):397-402.
Related landmarks
- 1987 · CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) (Cardiology)
- 1987 · FDA approval of lovastatin, the first statin (HMG-CoA reductase inhibitor) (Cardiology)
- 1988 · ISIS-2 (Second International Study of Infarct Survival) (Cardiology)
- 1991 · SOLVD Treatment Trial (Cardiology)