What was the study Question?
Does thrombolytic therapy in pulmonary embolism (PE), especially in those with hemodynamic stability and evidence of right ventricular (RV) dysfunction, really increase the rates of intracranial hemorrhage (ICH) without affecting mortality?
Why was the study needed?
A recent randomized controlled trial (RCT) suggested that when patients with intermediate risk PE were treated with thrombolytics versus anticoagulation therapy, there was an increase in bleeding without a decrease in mortality2. However, this study was not powered for mortality and, thus, the link between bleeding and mortality needed to be further investigated.
What were the main results?
Overall, thrombolytic therapy in PE was associated with lower mortality compared to anticoagulant therapy. The number needed to treat with thrombolytics for mortality was 59 with a number needed to harm for ICH at 78. Thus, the benefit appears to outweigh the risk in patients with PE and evidence of RV dysfunction.
What were the study’s strengths?
This is the first study to be powered to detect a mortality difference in patients undergoing thrombolytic therapy versus anticoagulation in patients with PE, even those with hemodynamic stability and RV dysfunction.
What were the study’s limitations?
span class="Apple-converted-space"> Dosages and methods of administration (systemic infusion vs. catheter-based) of the thrombolytics were not compared.
span class="Apple-converted-space"> Though previous studies have shown a higher bleeding risk in patients with intermediate risk PE, this study highlights the potential benefits of being more aggressive with thrombolytic therapy in this risk group. Because the absolute net clinical benefit is modest, in the individual patient an assessment of bleeding risk should be made prior to thrombolytic administration.
1. Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, Kumbhani DJ, Mukherjee D, Jaff MR, Giri J. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: A meta-analysis. JAMA : the journal of the American Medical Association. 2014;311:2414-2421
2. Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV, Investigators P. Fibrinolysis for patients with intermediate-risk pulmonary embolism. The New England journal of medicine. 2014;370:1402-1411