Anticoagulant heparin reduces the risk of death from complications of COVID-19 by 78% when given in therapeutic dose as soon as the patient arrives at the hospital with signs of respiratory failure, according to a study published this Thursday (14/10) in British Medical Journal.
Currently, the World Health Organization (WHO) recommends for these cases only a prophylactic dose of the drug (indicated to prevent thrombosis), which is four times lower than the therapeutic dose and showed no benefit in the randomized clinical trial. The research involved 465 patients treated in 28 hospitals in six countries, including Brazil.
“We believe these findings should change clinical practice,” says Dr Elnara Negri, co-author of the paper and team member of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (FM-USP) and the Faculty of Medicine, to the FAPESP Syrian-Lebanese Hospital.
The researcher points out, however, that the recommendation does not apply to everyone diagnosed with COVID-19. “The treatment is indicated only for those who are hospitalized and only under medical supervision. If a person takes anticoagulants without need or guidance, he can bleed to death ”.
Patients of both sexes, with a mean age of 60 years, who were admitted to hospital with 93% or less oxygen saturation, participated in the clinical study. The aim was to evaluate the effect of heparin on several possible outcomes of SARS-CoV-2 infection. In addition to reducing mortality, therefore, an attempt was made to observe whether the treatment reduced the need for non-invasive ventilation (with a high-flow catheter or oxygen mask), intubation and admission to intensive care (ICU).
The volunteers were divided into two groups, one receiving the therapeutic dose and the other receiving only the prophylactic dose (control group). The effect on outcomes was evaluated 28 days after drug administration.
“We did not see a significant difference in terms of the need for ICU admission, non-invasive ventilation or intubation. But the death toll was significantly lower in the group that received the therapeutic dose. And the occurrence of major bleeding, which was the main adverse effect observed in the study, was very low. In other words, the therapy is safe, ”says the doctor.
The results also show that heparin must be administered between the seventh and fourteenth day after the onset of symptoms to be beneficial. Previous studies had already shown that anticoagulation does not bring important results when performed after admission to the ICU.
The doctor points out that the benefits at this stage of the disease were only seen with the use of injectable heparin. Orally administered anticoagulants had no effect. “This is likely due to the fact that this drug also has antiviral and anti-inflammatory effects already confirmed in the context of COVID-19. The good news is that it is an inexpensive drug available in the SUS [Sistema Único de Saúde]. ”
In collaboration with colleagues from the FM-USP Department of Pathology, Marisa Dolhnikoff and Paulo Saldiva, Negri was one of the first people in the world to speculate that blood clotting disorders underlie the more severe symptoms of COVID-19. – among them respiratory insufficiency and pulmonary fibrosis. The group published the first article in the scientific literature describing “pathological evidence of pulmonary thrombotic phenomena in severe COVID-19” (for more: agencia.FAPESP.br/33175).
“The virus enters through the respiratory system and some organisms manage to contain it before it reaches the pulmonary alveoli. But when it invades the capillaries that supply the lung, it begins to make holes in the endothelium [camada de células que reveste a parte interna dos vasos] and this causes the blood to begin to clot. Form of microthrombi that prevent the passage of blood to the lung structures where gas exchange takes place ”, he explains.
Heparin helps prevent this from happening through two mechanisms: the drug breaks down the microthrombi that prevent oxygen from passing from the alveoli to the small pulmonary arteries and, in addition, aids in the recovery of the vascular endothelium.
Studies published over the past year indicate that around 15% of people infected with the new coronavirus develop changes in blood clotting. “This is the population that can benefit from heparin treatment, but timing is of the essence,” says Negri.
O artigo Efficacy of therapeutic heparin versus prophylactic heparin in death, mechanical ventilation or ICU admission in moderately ill patients with covid-19 hospitalized: randomized clinical trial RAPID pode ser lido em: www.bmj .com / content / 375 /bmj.n2400.