Wednesday, January 30, 2013

MOPETT – Half-Dose tPA for PE

It's not very often I read an article and decide to I'd like to incorporate it into my practice.  EMCrit covered this last month, but I reserved judgement until I had a chance to read the primary literature for myself.

This is the MOPETT trial – half-dose (?"safe dose") tPA for "moderate" pulmonary embolism.  We already know what to do for "massive" PE – full-dose thrombolytics when not otherwise contraindicated.  However, the data for full-dose thrombolytics in "submassive" PE is less conclusive.

These authors enrolled relatively ill PE patients – tachypneic, hypoxic, tachycardic patients with >70% thrombotic occlusion of lobar or main pulmonary arteries – but did not apply regularly applied measures of "submassive" – RV dysfunction, elevated troponins, elevated BNP.  Their primary outcome was long-term development of pulmonary hypertension, with mortality and bleeding as their secondary outcomes.  They dosed tPA at 50mg, rather than 100mg – 10mg bolus and 40mg infusion.

Their two cohorts were rather well matched.  Outcomes favored the thrombolysis group, with 16% subsequent pulmonary hypertension compared with 57% in the control group.  Mortality, recurrent pulmonary embolism, and bleeding complications were similar and at rates too low to detect a difference given the power of the study.

I'd like to start doing this.  I wish they published the troponin/BNP/RV dysfunction rates in the two cohorts to provide better context with the other submassive literature.  I also would have preferred to see this study registered with clinicaltrials.gov.  But, in a nice change, none of the authors declare any conflicts of interest!

"Moderate Pulmonary Embolism Treated With Thrombolysis (from the “MOPETT” Trial)"
www.ncbi.nlm.nih.gov/pubmed/23102885

4 comments:

  1. Great RCT, however has some big issues. Reduction in pHTN does not mean reduction in patient oriented outcomes. The patient could care less what his PASP is, he/she only wants to make sure they are not having dyspnea 6 months later. This is critical and has been largely unanswered by the literature. This is the only trial to show a mortality benefit and larger, high quality RCTs have not confirmed it. In fact, meta-analysis demonstrates no mortality benefit and no reduction in recurrent VTE. There is a 2% ICH rate (PEITHO trial) and major bleeding occurs with a NNH 15. For me, until data comes out showing a patient oriented benefit I find it hard to justify giving lytics when we know we have a NNH 15 and unproven benefits.

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    1. Valid criticisms – I would note, however, PEITHO uses full-dose thrombolytics. I have no qualms with folks who prefer to withhold therapy based on surrogate outcomes such as pHTN, particularly in a setting of possible small – but real – fatal bleeding complications.

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    2. Great post and important critiques. I have used half-dose lytics for submassive PE. The couple of times I've done it was on young patients with hemodynamic instability and evidence of right heart strain. I think this is a good place for shared decision making to come into play since we're not talking about mortality but rather long term morbidity. I think pulmonary HTN is a reasonable surrogate for patient functionality but I agree that it would have been nicer to see something like "ability to walk a mile without getting winded."

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    3. Ryan: PEITHO used 30-50mg rt-PA (TNK) which is reduced compared to usual 100mg rt-PA (alteplase). Am i missing something? As far as I know they only differ based on amino acid sites that increase fibrin specificity.

      Anand: I do believe a properly designed RCT would probably show improved patient outcomes (TOPCOAT hinted at such). Big question then becomes WHO benefits and by HOW much? And is the degree of benefit worth the risk of major bleeding. Probably not if it turns out they can only walk 5 more feet if they got the lytics. Lot of answered questions. I love the shared decision making....I'm just not sure you can tell the patient they will feel better 6 months later......yet!
      Like you I'm eagerly waiting good data to answer these questions....I suspect that you will both be proved right.

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