MAPPET-3

NEJM

October 10, 2002

Heparin Plus Alteplase Compared with Heparin Alone in Patients with Submassive Pulmonary Embolism.

Summarized by: 

Mazen Kherallah

What was the research question?

  • In patients with sub-massive PE, does the addition of alteplase hrombolysis to IV heparin, compared to heparin alone, reduce the composite outcome of mortality or clinical deterioration?

How did they do it?

  • A multicenter, double-blinded, randomized, controlled trial in 49 centers in Germany.

  • 256 patients with submassive pulmonary embolism and pulmonary hypertension or right ventricular dysfunction but without arterial hypotension or shock were randomized to receive heparin plus 100 mg of alteplase (118 patients) or heparin plus placebo (138 patients) over a period of two hours.

  • The primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment (catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter).


What did they find?

  • The incidence of the primary end point was significantly lower in the alteplase group compared to the placebo group (11% vs. 24.6%, P=0.006, NNT 7).

  • This difference was primarily driven by the escalation of treatment that was significantly lower in the alteplase group compared to the placebo group (10.2% vs. 24.6%, P=0.004). This in turn was predominately due to secondary thrombolysis (7.6% vs. 23.2%, P=0.001).

  • There was no significant difference in in-hospital mortality between the alteplase group compared to the placebo group (3.4% vs. 2.2%, P= 0.71).

  • Major bleeding events were not different in the alteplase group compared to the placebo group (0.8% vs. 3.6%, P=0.29).


Are there any limitations?

  • The trial was stopped early for significant improvement; therefore, it is under-powered.

  • Composite outcome is a limitation factor especially that it was not patient oriented.

  • Decision to give secondary thrombolysis as part of the escalttion of therapy was at the discretion of the treating physician rather than based on strict criteria.


What does it mean?

  • Alteplase in conjunction with unfractionated heparin in patients with submassive pulmonary embolism decreases the rate of escalation of treatment compared to heparin alone. Mortality and bleeding complications were not different than placebo.

  • Further evidence is required before this treatment can be recommended

MAPPET-3