EMCrit Wee – MOPETT Trial

The MOPETT Trial took sub-massive PE patients and randomized them to half-dose tPA vs. standard care. No bleeds in either group. 41% ARR of pulmonary hypertension at 28 months.

Study Description from the Author

PDF of his MOPETT presentation slides

 Does this change your game?

Update:

A new trial using a similar protocol showed benefit without complications (Clinical Cardiology Volume 37, Issue 2, pages 78–82, February 2014)

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Comments

  1. Josh Farkas says:

    Scott,

    Great post, thanks. My practice has been not to lyse sub-massive PE, but your blogs and emerging evidence have changed my mind.

    I *really* like LMWH for PE (1), and I’m glad to see it combined with lytics in the MOPETT trial (and your prior post with Jeff Kline). I wonder if uncontrolled yo-yo-ing of PTT with heparin drips causes more bleeding than thrombolytics.

    Best,
    Josh

    [1] Cochrane Database Syst Rev 2004; CD001100. LMWH vs heparin in PE ==> LMWH reduces major hemorrhage and mortality.

    • agree–i think heparin may be the more dangerous drug in these cases.

      • Neil Waldman says:

        Hi Scott- I just gave half strength TPA to a large PE in a young person here in New Zealand. I cannot get an urgent ultrasound at my small hospital. It was almost occluding her entire right main pulmonary artery. she was hypoxic but hemodynamically stable. She did fine but the internal medicine doctors (multiple) ripped my head off and officially complained to my ED director about me!! They said the MOPETT trial had been “discredited” because it’s results were so discordant with “other larger trials” that showed no benefit to RV on ultrasound, the best being a ” NEJM study”.-I cannot seem to find any of this. They said that “professional colleges” had official policy stances that lytics for submissive PE are officially NOT sanctioned.

        The ED literature seems to be very positive for lyrics for submissive PE…have you heard of these other better studies and of official policy statements?? Are they bullshitting me?? do I need to feel stupid and humbled???

  2. Great post thanks as always for the superb education.

    So would you start ordering Echo’s on all PE pts to see if they meet criteria? Also where/what do you think is the optimal time to lyse, in the ED? Inpatient? clearly these are stable patients… It would also seem like we would need to get Pulmonary buy-in at our own shop before starting something like this..

    • Echo should be done bedside by ED doc. If you are having trouble visualizing or are not there yet with your echo skills, then any sig. sized clot should signal the need for an echo. I lyse in the ED, I think its fine to wait till ICU, but we are much more familiar with lytics and administration.

  3. Great podcasts! My practice (probably influenced by routine bedside ultrasound – hard to ignore the pathetic little LVs crushed in a corner by massive RVs) had been to lyse patients with RV:LV ratios above 1 – they just seemed a lot sicker. It was impressive to see the RV dysfunction improve significantly almost every time. Nice to have some evidence to back it up!

    thanks Scott!

  4. Patrick Burkhardt says:

    Hey Scott-
    I don´t understand the inclusion criteria (and definition of “sub-massive”):
    1) Thrombus on CT + 2 clinical criteria OR
    2) CT + 2 clinical criteria + elevated BNP or Trop I or right heart strain on echo?
    My definition of “sub-massive” PE would be 2), 1) being “mild” – but I don´t seem to get it from the abstract and slides.
    If it´s 1), the *average* PASP seems quite high to me. When I do echo for evaluation of SOB, and see RV enlargement *and* PASP over 60, I tend to think “chronic” and would ask for more PE indicators to send them to CT. If it´s right heart strain and PASP below 40, they go to CT directly. http://spo.escardio.org/eslides/view.aspx?eevtid=40&fp=P4495
    But of course, if they had included patients I would call “mild”, that would make the results even more impressive.
    I think I will present this at my hospital and start half-dose lysing PEs with right heart strain. Hell, we lyse strokes with (IMO) a fraction of the evidence!
    A good new year to you and yours,
    Patrick

    • Agree. These pts are milder than I would normally consider lysis in. They seemed to enter more based on clot size/density than bad signs. I think this is why they called them “moderate” rather than sub-massive as the latter requires the echo/marker signs of heart dysfunction. You would know better than I whether PASP can differentiate chronic vs. acute. I have always looked at RV wall thickness as my arbiter.

      • Patrick Burkhardt says:

        Agreed. Free RV wall thickness, regional wall motion abnormalities as in McConnells sign and TAPSE can all be helpful. But if patients can´t be properly positioned, apical views are often not good especially free RV wall (I call it “The dark territory”). Subcostal view is often best.
        But I think ist makes sense that without chronic cor pulmonale the RV will usually not manage to perform > 60 mmHg of PASP. Of course, patients with cor pulmonale can also have acute PE. I just wondered about the high number of pts with PAH in this group.

  5. Great podcast. If I was having a moderate PE I would much prefer lysis. Gets rid of all that remaining DVT too and might help prevent post phlebitic syndrome in the limbs.
    I have always understood that there is a higher bleeding risk with lysing PE compared to coronary lysis, because when a clot is lysed the FDPs are themselves anticoagulant. This wouldn’t matter with a small clot such as you find inside coronary arteries, but when a large clot is lysed ie not just the PE but the whole remaining DVT in the leg, then this is probably a bleeding risk which explains why half dose lysis was chosen I suppose.

    • Based on Klines look at complications, even full dose has an extremely low complication rate. It is in stroke where we can do a lot of damage with tPA.

  6. Well Goldhaber I think did full dose and didn’t get any bleeds in anyone under age 56yrs. (that was a very old article though that I read years ago), however I guess the risk is theoretical ie if a large clot when lysed does in fact anticoagulate one more from it’s FDPS (and I don’t recall where I read that) then it stands to reason you would choose a lesser dose.

  7. Eli Segal says:

    Thanks for the Podcast. Great work.
    Can you please clarify in your podcast the indications for inclusion in the study. ‘Moderate PE’ in the published article is based upon CT or VQ findings, whereas “RV enlargement or hypokinesia and elevation of biomarkers of RV injury (troponin I and brain natriuretic peptide), although measured, were not a requirement for enrollment”.
    I find the VQ criteria weaker than the CT ones, and it would have been interesting to see how many patients were investigated by either modality. However, the results do seem to suggest a strong benefit with little harm.

    • Yeah, I thought that was weird as well. They went by PE size/location rather than markers of RV dysfunction, that’s why they use the weird name rather than submassive.

      • Wouldn’t it make sense to at least use location as one indicator for inclusion in the study as its based on the assumption that the lungs (and therefore the embolism) receive the complete cardiac output and thus are exposed to the entirety of the the t-PA (on first pass). If you included had small subsegmental clots, even if they resulted in RV strain, you could no longer assume that they would be receiving the entire lytic dose. A large segmental clot should theoretically be exposed to 1/5th of the pulmonary circulation (not accounting for gravitational flow of blood) and be closer to the 15% CO cited in the author’s notes on this article in the following pdf.

        http://emcrit.org/wp-content/uploads/2012/12/Sharifi_MOPETTstudy.pdf

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