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Therapeutics

Tissue-plasminogen activator reduced mortality rates compared with streptokinase for acute myocardial infarction

ACP J Club. 1997 Jan-Feb;126:3. doi:10.7326/ACPJC-1997-126-1-003


Source Citation

Califf RM, White HD, Van de Werf F, et al., for the GUSTO-I Investigators. One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) Trial. Circulation. 1996 Sep 15;94:1233-8.


Abstract

Objective

To compare the 1-year mortality rates for patients with acute myocardial infarction (MI) who were treated with accelerated tissue-plasminogen activator (tPA) plus intravenous (IV) heparin, streptokinase plus subcutaneous heparin, streptokinase plus IV heparin, or tPA plus streptokinase plus IV heparin.

Design

1-year follow-up of a randomized controlled trial (Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries [GUSTO-I] trial).

Setting

{1081 hospitals in 15 countries.}*

Patients

41 021 patients who had acute MI and presented within 6 hours of symptom onset with ST-segment elevation were enrolled in the GUSTO-I trial. Exclusion criteria included history of stroke, active or recent bleeding or major coagulation abnormality, recent trauma or surgery, noncompressible vascular punctures, or previous treatment with streptokinase or anistreplase. 37 979 patients survived to 30 days (mean age 61 y, 76% men). Follow-up was 96%.

Intervention

Patients were allocated to 1 of 4 treatments: streptokinase, 1.5 × 106 U for 60 minutes, plus subcutaneous heparin, 12 500 U twice daily (SK-SQ) (n = 9080); streptokinase in the same regimen plus IV heparin, bolus dose of 5000 U and an infusion of 1000 U/h, with the dose adjusted to maintain an activated partial thromboplastin time of 60 to 85 seconds (SK-IV) (n = 9607); accelerated tPA, bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes and 0.5 mg/kg for 60 minutes, plus IV heparin (accelerated tPA) (n = 9695); or IV tPA, 1.0 mg/kg for 60 minutes, 10% given as bolus, plus streptokinase, 1.0 × 106 U for 60 minutes, plus IV heparin (combination therapy) (n = 9597).

Main outcome measure

1-year mortality rate.

Main results

Analysis was by intention to treat. The 30-day and 1-year mortality rates were 6.3% and 9.1% for patients who received accelerated tPA, 7.2% and 10.1% for patients who received SK-SQ, 7.4% and 10.1% for patients who received SK-IV, and 7.0% and 9.9% for patients who received combination therapy (for accelerated tPA compared with SK-SQ, P = 0.011; for accelerated tPA compared with SK-IV, P = 0.009). The difference in mortality rates between patients who received accelerated tPA and those who received combination therapy was of marginal statistical significance (P = 0.05). The mortality rates associated with combination therapy did not differ from those associated with streptokinase (P = 0.47).

Conclusion

Accelerated tissue-plasminogen activator was more effective than streptokinase for acute myocardial infarction; the lower 30-day mortality rate was maintained at 1 year.

Sources of funding: Bayer; CIBA-Corning; Genentech; ICI Pharmaceuticals; Sanofi Pharmaceuticals.

For article reprint: Dr. R.M. Califf, Box 31123, Duke University Medical Center, Durham, NC 27710, USA. FAX 919-286-4838.

*From N Engl J Med. 1993;329:673-82.


Commentary

In the evidence-based era, the GUSTO-I trial sets a high standard for comparison of a new treatment with standard therapy. Administration of the accelerated tPA regimen soon after acute MI results in a substantial mortality advantage within 24 hours and a more prominent effect at 30 days. This trial shows that this early benefit continues at 1 year. Previous trials that compared thrombolysis with placebo have shown that the benefit is maintained for as long as 5 years (1). We will wait to see whether the same also holds true for the GUSTO trial results.

Should tPA be considered the thrombolytic agent of choice if medical reperfusion therapy is chosen for an appropriate patient? The cost differential between tPA and SK and the modest treatment advantage (number needed to treat with tPA to prevent 1 additional death = 100) makes this a difficult choice. Given the multiplicity of health care systems (hospital, third-party payers, city, region, country), there is no "right" answer to the question that can apply to all patients. Ultimately, the optimal decision can only be made in the context of a particular health care system.

Issues of selection of one agent over another should not distract us from pursuing additional strategies to maximize the potential of thrombolytic therapy in acute MI, including 1) public awareness campaigns of the warning signs of acute MI and the importance of promptly seeking medical attention; 2) ensuring that hospitals that routinely accept responsibility for patients with acute MI can promptly administer thrombolysis and handle complications; 3) expeditiously triaging all patients who are potentially eligible for thrombolysis; and 4) having institutions review and appropriately modify their decision-making and administrative processes to ensure prompt and efficient initiation of thrombolytic therapy.

David Massel, MD
London Health Sciences CentreLondon, Ontario, Canada


Reference

1. Simoons ML, Vos J, Tijssen JP, et al. J Am Coll Cardiol. 1989;14:1609-15.