Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713

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Current Issue: 2019 - Volume 45 - Number 1 (January/February)

AUTHOR'S REPLY

Authors' reply: Reflections on the use of thrombolytic agents in acute pulmonary embolism

Resposta dos autores: Reflexões sobre o uso de trombolítico na embolia pulmonar aguda

 

Caio Julio Cesar dos Santos Fernandes1; 2; a; Carlos Vianna Poyares Jardim1; b; José Leonidas Alves Jr1; 2; c; Francisca Alexandra Gavilanes Oleas1; d; Luciana Tamie Kato Morinaga1; e; Rogério de Souza1; f

 

1. Unidade de Circulação Pulmonar, Disciplina de Pneumologia, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de
São Paulo, São Paulo (SP) Brasil.
2. Instituto do Câncer, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.
a. http://orcid.org/0000-0002-4912-021X; b. http://orcid.org/0000-0003-0425-5548; c. http://orcid.org/0000-0001-8943-1947;
d. http://orcid.org/0000-0002-1385-5222; e. http://orcid.org/0000-0002-0900-2737; f. http://orcid.org/0000-0003-2789-9143


 

 

 

The use of systemic thrombolytic agents for the treatment of acute pulmonary embolism is a controversial subject, in which evidence and belief eventually clash. While there is no dispute regarding the benefits of the procedure for high-risk patients,(1) this indication is much more debatable for intermediate-high-risk patients. These latter patients are characterized by maintaining adequate levels of tissue perfusion at the expense of right ventricle injury. It is quite tempting to imagine that pharmacological intervention at this point would prevent progression to right ventricular failure, cardiovascular collapse, and death. It is also intuitive to seek a long-term benefit from the use of thrombolysis in intermediate-high-risk patients; after all, by reducing the thrombotic load, it would be possible to reduce any residual vascular obstruction, thereby reducing the risk of chronic thromboembolic pulmonary hypertension. However, thrombolysis indisputably increases the risk of bleeding. So what to do? The physiological rationale is not always the best path to take. In such cases, seeking the best evidence available can provide better answers.

The study by Meyer et al.(2) is the largest and best study to date to evaluate thrombolysis versus heparin therapy in intermediate-risk patients systematically, although it is not the only one.(1) The number of patients evaluated in the study by Meyer et al.(2) is larger than the total number of patients in all studies that investigated alteplase, the most traditionally used drug in such cases (1006 vs. 657). This results in tenecteplase being the most commonly investigated thrombolytic agent in phase III trials in pulmonary embolism today. In addition, because of the large number of patients, the study by Meyer et al.(2) has an 80% power of detection of intergroup differences. All those studies, with the one by Meyer et al.(2) being the most representative, tend to converge on the same finding: while the use of thrombolytic agents poses an increased risk of bleeding, which is greater in the population known to be at risk, such as the elderly, the benefits of thrombolysis, whether with alteplase, tenecteplase, urokinase, or streptokinase, appear to be quite modest. Traditional heparin therapy appears to be quite safe, with a mortality rate of 1.8% if good medical practices are followed. Monitoring of intermediate-high-risk intensive care patients and prompt institution of reperfusion at the first sign of hemodynamic instability are mandatory prerequisites. However, if these prerequisites are met, and with such low mortality rates, is it worth performing thrombolysis, since conventional therapy is effective? The most reasonable solution appears to be conventional therapy, intensive monitoring, and early reperfusion if there is any sign of hemodynamic instability. And, as suggested earlier, it is possible that lactate levels play a role in this monitoring.

Long-term benefits also do not justify the use of thrombolysis. Data from a study by Konstantinides et al.(3) identified no benefits in mortality rates, residual dyspnea, or diagnosis of chronic thromboembolic pulmonary hypertension. If the short-term benefit is small, the medium-term benefit is zero, and there is the risk of further morbidity, such as bleeding, why do it indiscriminately? Of course, if the choice if for thrombolysis, hemorrhage should be prevented by dose adjustment for weight and age, pressure control, and use of a proton pump inhibitor. Even so, does the benefit justify the risk? To date, the best available evidence tells us that it does not.

REFERENCES

1. Fernandes CJCDS, Jardim CVP, Alves JL Jr, Oleas FAG, Morinaga LTK, Souza R. Reperfusion in acute pulmonary thromboembolism. J Bras Pneumol. 2018;44(3):237-243. https://doi.org/10.1590/s1806-37562017000000204
2. Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-11. https://doi.org/10.1056/NEJMoa1302097
3. Konstantinides SV, Vicaut E, Danays T, Becattini C, Bertoletti L, Beyer-Westendorf J, et al. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol. 2017 Mar 28;69(12):1536-1544. https://doi.org/10.1016/j.jacc.2016.12.039

 

 


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