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Welcome new blog team member: Dr. Salim Rezaie

Posted Mar 13 2013 12:00am


There was recently a great study published in the American Journal of Cardiology (2012) by Sharifi et al , questioning whether we should be considering tPA in patients other than those patients with massive pulmonary embolism (PE)? You know the big “Saddle Embolus” we all fear? Well it turns out this is only about 5% of all PEs and although it has the highest mortality, should we be considering tPA in patients with sub-massive PEs?

Sharifi and colleagues hypothesized that “1/2 dose tPA” could be used for PEs.

Why half dose of tPA you ask? 
It turns out that pulmonary blood flow is 100% of cardiac output, making pulmonary arteries very sensitive to lysis. In considering that the brain only uses about 15% of the cardiac output and the heart even less than that at 5%, do we really need to use “full dose” tPA (100 mg) in the lungs?

Methodology
This was a prospective, randomized clinical trial looking at 121 patients, which were randomized to treatment group or control group. The 61 treatment group patients received tPA 10 mg over one minute followed by the rest of the dose over two hours, followed by lovenox or heparin. The control group received no lytics and the treatment dose of lovenox or heparin.

Results
There was a decrease in baseline pulmonary artery systolic pressure (PASP) of 22 mmHg in the treatment arm and 8 mm Hg in the control arm at 28 month follow up. This led to an absolute risk reduction (ARR) of 41%.

Not bad you say. Well, there was NO statistical improvement in overall mortality. As far as the secondary outcomes, there was no major bleeding or intracranial hemorrhage in either group and the hospital length of stay was also shortened in the treatment group by about 2.7 days.

Bottom line on MOPETT study
Half-dose tPA is likely safe and but of questionable clinical benefit.

But wait, look what's hot off the press: PEITHO study
The PEITHO (Pulmonary EmbolIsm THrOmbolysis) study data was just presented at the American College of Cardiology 2013 Scientific Sessions. This is the largest study looking at sub-massive PEs and use of thrombolytics, conducted over 10 years. In this study, sub-massive PE comprised about 15 to 20% of all PEs, and patients were at high risk for death and cardiovascular collapse.

This was a prospective, multicenter study of just over 1000 patients who were randomized to a FULL, weight-dosed bolus of tenecteplase plus heparin (treatment arm) versus just heparin alone (control arm). The primary endpoint evaluated was the combined endpoint of death from any cause and hemodynamic collapse at 7 days.
Video (16:23 min) from TheHeart.org  interviewing primary PEITHO investigator Dr. Stavros Konstantinides
The relative risk reduction (RRR) of the primary endpoint was about 56%, but as we are always cautioned about RRR, the actual numbers show primary endpoint rates of 2.6% in the treatment arm and 5.6% in the control arm, which is an ARR of only 3%. Unfortunately, the rate of major bleeding was significantly higher in the treatment arm (6.3%) compared to the control arm (1.5%).

So are lytics in sub-massive PE ready for primetime? 
My opinion is we are not there yet. Several studies now have shown the risk of major bleeding with lytics, but no real significant improvement in mortality. Let's see what else we have coming up in the pipeline in the near future. Remember our job as physicians is to do no harm, and right now the evidence says we are doing more harm than good with full-dose lytics in sub-massive PE.

________________________________
Coincidentally, this article was also discussed at the 2013 Bay Area EM Residency Journal Club last night with UCSF-SFGH, Stanford-Kaiser, and Highland. See the Twitter discussion
[ View the story "MOPETT and PLEITHO studies on lytics and submassive PEs" on Storify ]

-- Salim R. Rezaie, MD (Twitter:  @srrezaie )

References:
  1. Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7.  PMID 23102885  
  2.  Nainggolan, Lisa.  PEITHO: Persuasive for Thromblolysis inPE?   Heartwire Mar 2013.
  3. Video: http://www.theheart.org/columns/clot-blog/peitho-thrombolysis-in-pe.do
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