A “historical milestone” for stroke patients in Brazil was achieved recently, with the country’s Ministry of Health (MOH) publishing Order 1.996/2023 on 24 November to add mechanical thrombectomy to the list of procedures covered by the Brazilian public health system (Sistema Único de Saúde [SUS]). As stated in a World Stroke Organization (WSO) press release, “this achievement crowns the efforts of a tireless network of stroke neurologists and neurointerventionists”.
In 2013—following three international trials that ultimately produced negative findings on mechanical thrombectomy—Raul Nogueira (University of Pittsburgh Medical Center, Pittsburgh, USA) and Sheila Martins (Federal University of Rio Grande do Sul, Porto Alegre, Brazil) started designing the RESILIENT clinical trial to test thrombectomy in acute ischaemic strokes caused by large vessel occlusions (LVOs). Their goal was for the trial to be implemented in the public health system in Brazil.
The Brazilian MOH had published Orders 664 and 665 one year before, including the reimbursement of alteplase for acute ischaemic stroke and establishing criteria to subsidise the implementation of stroke centres. Martins, an MOH advisor at the time and now WSO president, approached the ministry to secure funding for the national, randomised RESILIENT trial in Brazil. The MOH accepted the proposal in 2014, and negotiated with Medtronic and Penumbra to donate thrombectomy devices for use in the trial. Concurrently, the ministry also established the National Stroke Research Network under the coordination of WSO Education Committee co-chair Octávio Marques Pontes Neto (University of São Paulo, Brazil).
Constraints in ethical and regulatory procedures delayed the RESILIENT trial’s commencement, with certain devices not being registered in Brazil. However, five pivotal thrombectomy studies were published between October 2014 and April 2015, establishing the safety and effectiveness of the treatment at a time when the RESILIENT trial was already prepared to start. With those results in hand, a group led by RESILIENT principal investigators Martins and Nogueira approached the MOH again to request the implementation of thrombectomy care.
The Brazilian government was not satisfied with the findings of these studies, conducted in high-income countries, because several questions remained unanswered regarding such a costly procedure: Would the national prehospital delays in diagnosis, triage and transportation; the vulnerability of Brazil’s patient population; the low-resource in-hospital setting; the lack of access to postprocedural care and rehabilitation; and the lack of trained neurointerventionists, affect the results? Were the findings translatable for low- and middle-income countries? Was the procedure cost effective in a public healthcare setting?
“In this sense, the RESILIENT trial was demanded by the Brazilian MOH,” the recent WSO release notes. “The stroke neurologists and neurointerventionists worked hard to reorganise and train the stroke services, and the network to be prepared for the new treatment. Raul Nogueira and the president of the Brazilian Society of Neurointervention, Francisco Mont’Alverne—together with experienced neurointerventionists Daniel Abud, Michel Frudit, Pedro Magalhães, and Leandro Barbosa—provided training to the entire group for the procedure, offering 24/7 telemedicine support in real time for complex cases.”
The release also highlights the fact that RESILIENT’s executive committee and working group—including multiple members and future leaders of the WSO—were available to discuss cases and assist in patient selection. In addition, the study hosted a “special international collaboration” via its data safety monitoring board (DSMB), clinical events committee (CEC), and image adjudication.
The RESILIENT trial recruited its first of 221 patients in February 2017, and was terminated after the first interim analysis due to results overwhelmingly favouring the thrombectomy group. These findings were published in the New England Journal of Medicine in 2020, and the procedure was later proven cost effective in a study published in the International Journal of Stroke by Ana Claudia de Souza (Federal University of Rio Grande do Sul, Porto Alegre, Brazil) and colleagues.
In 2021, the National Commission for the Incorporation of Technologies in the Unified Health System (CONITEC) recommended the incorporation of thrombectomy in the SUS—promptly followed by a favourable decision from the Secretary of Science, Technology, Innovation and Strategic Health Supplies of the MOH to make the treatment available up to 24 hours from symptom onset in LVO acute ischaemic stroke patients.
“Public resources are limited, which was the main reason for the gap between the decision to implement mechanical thrombectomy and its practical implementation in SUS,” the WSO release continues. “The articulation with the federal government—led by the Brazilian Stroke Society, Brazilian Stroke Network, and Brazilian Academy of Neurology, among other societies, politicians and professionals—was critical, as [was] the openness of the MOH to the dialogue. Order 1.996/2023 establishes the reimbursement standards, enables 12 public stroke centres to start offering the procedure promptly, and paves the way for additional stroke centres to submit their interest.
“The legacies of the RESILIENT trial are outstanding. For the scientific field, a research network was created and is pushing forward relevant randomised clinical trials that inspire other low- and middle-income countries to do the same. In terms of populational health, it aims to substantially reduce the burden of stroke in the country, and serve as inspiration to societies and governments worldwide to implement mechanical thrombectomy for acute ischaemic stroke.
“The success of the implementation of mechanical thrombectomy in SUS is a history of translation from research to practice; from impact factor to populational impact; from dream to reality.”
