Skip to content
Evevident
Original paper
1988LancetCardiology

ISIS-2

Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2

RCTAcute myocardial infarction

On this page

Overview

In acute MI, aspirin and streptokinase each reduced early vascular mortality, with additive benefit together.

Clinical takeaway

ISIS-2 made early aspirin a lifesaving default in suspected acute MI and established fibrinolysis as mortality-reducing therapy before the primary PCI era.

Key result

Both aspirin and streptokinase reduced 5-week vascular mortality; the combination reduced mortality from 13.2% to 8.0%.

Practice impact

Give aspirin immediately in suspected MI unless contraindicated; fibrinolysis became a reperfusion standard where PCI is unavailable.

Evidence

Study design

Large randomized, placebo-controlled 2-by-2 factorial trial.

Enrollment

17,187

Follow-up

5 weeks for primary mortality reporting.

Geography

Multinational

Clinical question

In suspected acute myocardial infarction, do early aspirin, streptokinase, or both reduce vascular mortality?

Population

  • Patients with suspected acute myocardial infarction presenting within 24 hours of symptom onset.

Intervention

Streptokinase infusion, aspirin 160 mg daily for one month, or both.

Comparator

Placebo infusion, placebo tablets, or neither active treatment.

Primary outcome

5-week vascular mortality.

The combination of aspirin and streptokinase produced additive early mortality reduction after suspected acute MI.

Odds reduction / 42 / CI 95% CI 34-50% / p=<0.0001

Key results

  • Streptokinase reduced vascular mortality from 12.0% to 9.2%.
  • Aspirin reduced vascular mortality from 11.8% to 9.4%.
  • Both active treatments reduced vascular mortality from 13.2% to 8.0%, an odds reduction of about 42%.

Harms

  • Streptokinase increased bleeding requiring transfusion and rare cerebral hemorrhage.

Clinical Use

When to cite

  • When explaining why aspirin is given immediately in suspected acute coronary syndrome.
  • When teaching the historical evidence for fibrinolysis in STEMI.

Practice impact

  • Established immediate aspirin as standard care for suspected acute MI.
  • Helped define fibrinolysis as mortality-reducing reperfusion therapy before widespread PCI.

Applicability

  • Most useful historically and in settings where fibrinolysis remains relevant for STEMI without timely PCI.

Limitations

  • Pre-dates primary PCI, modern P2Y12 inhibitors, high-intensity statins, and contemporary anticoagulation.
  • Included suspected MI, not only biomarker-confirmed MI.

Common misinterpretations

  • Do not cite ISIS-2 to choose fibrinolysis over timely primary PCI in contemporary systems; cite it for the mortality benefit of early aspirin and reperfusion.

Related evidence

PLATO - Later TrialCURE - Later Trial

Citation

Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349-360.

Their separate effects on vascular deaths appeared to be additive.