Title: Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study

Settings: Retrospective observational study from a combination of Abbott Northwestern Hospital and 15 others as part of the Mayo Health system.

Participants: Patients between 2012 – 2020 who were treated for PE. Patients were propensity-matched according to the probability of a patient receiving a reduced- dose of alteplase.

Outcome measurement: 

• Primary outcome: all-cause and PE-related mortality or hemorrhage within 7 days of alteplase administration.
• Secondary outcomes: shock index at 8 hours after alteplase administration, LOS.

Study Results:

• A total of 284 patients were included in the retrospective analysis; 98 were treated with the full-dose and 186 with the reduced-dose alteplase regimen.
• Primary outcome was similar in both groups:
  • 7-day all-cause (5.6% in full- dose vs. 8% in reduced-dose, p = 0.45) 
  • PE-related (4% in full-dose vs. 4.2% in reduced-dose, p = 0.93)
• All other secondary outcomes were similar between both groups
• overall rates of hemorrhagic complications were significantly lower in the reduced-dose group than in the full-dose group (13% vs. 24.5%, respectively, p = 0.014).
• Major intracranial hemorrhage was higher, but not statistically significant, for full-dose group: 1.3% in reduced-dose vs. 7.1% in full-dose for major, (p = 0.067)

Discussion:

• Overall, there was more risk for full-dose. However, this is a retrospective study so whether it will be factored into clinical practice remains to be seen.
• The PERT team at UMMC still recommends full dose for hemodynamic unstable patients. Perhaps for those with somewhat instability, a half dose should be considered?
• There is still not enough data regarding the newer ones, as UMMS hospitals are starting to use TNK more frequently nowadays.

Conclusion: 

In this retrospective, Propensity-score matching study, the full-dose regimen but is associated with a lower risk of bleeding.

References

Melamed R, Tierney DM, Xia R, Brown CS, Mara KC, Lillyblad M, Sidebottom A, Wiley BM, Khapov I, Gajic O. Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study. Crit Care Med. 2024 May 1;52(5):729-742. doi: 10.1097/CCM.0000000000006162. Epub 2024 Jan 3. PMID: 38165776.