Review Article of Note

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Meyer G(1), Vicaut E, Danays T et al for the PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.

CONCLUSIONS: In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. PMID: 24716681

Comments: Lytics are beneficial in massive PE (i.e. with hemodynamic instability), but what about submassive, defined as PE with normal BP but evidence of RV dysfunction or RV injury? Death or hemodynamic decompensation occurred in 2.6% of the tPA + anticoagulant vs. 5.6% in the placebo + anticoagulant group, NNT = 33.3.  But 6.3% of tPA patients had extracranial bleeding vs. 1.2% placebo and stroke (mostly hemorrhagic) in 2.4% tPA vs. 0.2% placebo, NNH bleed = 19.6, NNH stroke = 45.5.  For now, systemic tPA in submassive PE is not safe.  Endovascular lytics or lower dose lytics may be an option in the future.


Righini M, Van Es J, Den Exter PL et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014 Mar 19;311(11):1117-24. doi: 10.1001/jama.2014.2135.

CONCLUSIONS: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism. PMID: 24643601

Comments: The D-dimer cut-off for all is 500ng/mL, but it is known that D-dimer normally increases with age.  Of patients with the age-adjusted D-dimer (age X 10), only 1/331 (0.3%) subsequently had PE.  For patients with "unlikely PE" on simplified Well's score with normal age-adjusted D-dimer, PE is ruled out.


Sharifi M, Bay C, Skrocki L, Rahimi F et al for the “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027. Epub 2012 Oct 24.

CONCLUSIONS: In conclusion, the results from the present prospective randomized trial suggests that "safe dose" [50mg] thrombolysis is safe and effective in the treatment of moderate PE, with a significant immediate reduction in the pulmonary artery pressure that was
maintained at 28 months.

Comments: The FDA approved dose for massive PE is 100mg.  Whether half-dose tPA makes a difference in so called "moderate PE" is not known.  The authors found that the incidence of pulmonary hypertension was reduced even out to 28 months in these patients, NNT = 2.4.  There has been much discussion and controversy about this article. See Kline's discussion on EMRAP.  He points out some anomalies with this study that call into question some of the conclusions.


Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC, Richman PB, O'Neil BJ, Nordenholz K. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6(5):772-80.


Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ, RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-52.


Stein PD, Fowler SE, Goodman LR et al for the PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354(22):2317-27.

CONCLUSIONS: In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA-CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results. PMID: 16738268

Comments: Previously, PIOPED used V/Q scan as the imaging study.  Could CTA/CTV be used alone to diagnose PE?  "The sensitivity of CTA-CTV for pulmonary embolism was 90%, and specificity was 95%"  But in the era of multi-row CT scanners, the sensitivity of CTA alone is adequate.  CT pulmonary angiogram is now the imaging study of choice for PE diagnosis.


Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001;135(2):98-107.

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