Letter to the Editor
Sacubitril/valsartan: A practical guide revisited
Sacubitril/valsartan: um guia prático revisitado
Cândida Fonsecaa,
, Dulce Britob, Jorge Ferreirac, Fátima Francod, João Moraise, José Silva Cardosof, Expert opinion endorsed by the Heart Failure Study Group of the Portuguese Society of Cardiology
Autor para correspondência
a Clínica de Insuficiência Cardíaca, Serviço de Medicina III e Hospital Dia, Hospital São Francisco Xavier – Centro Hospitalar de Lisboa Ocidental, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Portugal
b Serviço de Cardiologia, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte, CCUL, Faculdade de Medicina da Universidade de Lisboa, Portugal
c Hospital de Santa Cruz – Centro Hospitalar de Lisboa Ocidental, Serviço de Cardiologia, Portugal
d Hospital Universidade de Coimbra – Centro Hospitalar e Universitário de Coimbra, Serviço de Cardiologia, Coimbra, Portugal
e Centro Hospitalar de Leiria, Serviço de Cardiologia, Leiria, Portugal
f Clínica de Insuficiência Cardíaca e Transplante, Centro Hospitalar de São João, Serviço de Cardiologia, Faculdade de Medicina da Universidade do Porto, Portugal
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Lisboa Norte, CCUL, Faculdade de Medicina da Universidade de Lisboa, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital de Santa Cruz – Centro Hospitalar de Lisboa Ocidental, Serviço de Cardiologia, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Universidade de Coimbra – Centro Hospitalar e Universitário de Coimbra, Serviço de Cardiologia, Coimbra, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Centro Hospitalar de Leiria, Serviço de Cardiologia, Leiria, Portugal" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Clínica de Insuficiência Cardíaca e Transplante, Centro Hospitalar de São João, Serviço de Cardiologia, Faculdade de Medicina da Universidade do Porto, Portugal" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Sacubitril/valsartan: um guia prático revisitado" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Since the publication in the May 2019 issue of our paper “Sacubitril/valsartan: a practical guide”,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> which was based on the PARADIGM-HF<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> trial results, new evidence has become available with recent data from the TRANSITION and PIONEER-HF trials.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3,4</span></a> On the basis of this new evidence, as the authors of the original practical guide we would like to add new considerations to our previous recommendations on the use of this drug.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although it represents a worsening of prognosis in heart failure with reduced ejection fraction (HFrEF), hospitalization for acute heart failure constitutes an opportunity to initiate and successfully up-titrate guideline-recommended therapies. The international guidelines support the initiation and up-titration of all disease-modifying therapy (DMT) early after hemodynamic stabilization following an acute heart failure event in order to improve prognosis, particularly during the vulnerable phase early after discharge.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> Although this has been demonstrated for previous classes of heart failure DMT, there was still a gap in evidence on the optimal time for the initiation of sacubitril/valsartan in HFrEF patients after an acute decompensation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The TRANSITION and PIONEER-HF trials evaluated the initiation of sacubitril/valsartan in severe HFrEF patients after stabilization following an acute heart failure episode, both before and early after discharge, with no run-in phase, closer to the challenges of everyday clinical practice.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The TRANSITION study assessed the safety and tolerability of sacubitril/valsartan in patients admitted with HFrEF, after stabilization following an acute heart failure episode. Patients were enrolled to initiate sacubitril/valsartan either in the hospital or shortly after discharge.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> At 10 weeks, when more than 86% of patients had been receiving sacubitril/valsartan for two weeks or longer without interruption, about half the patients in the study had achieved the primary endpoint, which was a target dose of 200 mg of sacubitril/valsartan twice daily within 10 weeks in both groups.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> The incidence of adverse events and discontinuation of sacubitril/valsartan due to adverse events was also similar in both in-hospital and outpatient settings.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> The tolerability of sacubitril/valsartan in TRANSITION appears to be comparable to that reported for beta-blockers and ACEIs/ARBs under real-life conditions.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3,7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">PIONEER-HF was designed to assess the safety, tolerability and efficacy of in-hospital initiation of sacubitril/valsartan compared to enalapril in stabilized HFrEF patients who had been admitted for acute decompensation.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> The primary endpoint was the time-averaged proportional change in NT-proBNP from baseline through weeks 4 and 8.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4,8</span></a> Patients treated with sacubitril/valsartan achieved a 47% reduction from baseline in time-averaged NT-proBNP, compared to a 25% reduction with enalapril, translating into a statistically significant 29% greater reduction with sacubitril/valsartan over the ACEI (95% CI: 0.63-0.81; p<0.0001).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> Significant reductions in NT-proBNP were observed in sacubitril/valsartan patients as early as one week after treatment initiation.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> There were no new safety signals identified, and the safety profile was comparable to that observed in PARADIGM-HF.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2,4</span></a> Rates of serious adverse events occurring with a frequency of ≥0.5% were similar between the sacubitril/valsartan and enalapril groups.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In a pre-specified exploratory analysis, the composite endpoint of death, rehospitalization for HF, left ventricular assist device implantation or listing for cardiac transplant occurred in 41 (9.3%) patients in the sacubitril/valsartan group and in 74 (16.8%) in the enalapril group (HR 0.54, 95% CI 0.37-0.79; p=0.001).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> The benefit was driven by reductions in death and rehospitalization among patients treated with sacubitril/valsartan. The number needed to treat to prevent one such clinical event during eight weeks of follow-up was 13.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Moreover, TRANSITION and PIONEER-HF are the first randomized studies to provide data on the use of sacubitril/valsartan in new-onset and ACEI/ARB-naive HFrEF patients. In fact, approximately 34% of patients in PIONEER and 29% in TRANSITION were newly diagnosed, with no prior history of heart failure, and slightly more than 50% of patients in PIONEER and 24% in TRANSITION were not receiving ACEI/ARB therapy at the time of admission.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3,4</span></a> Recently presented data from PIONEER-HF also showed that sacubitril/valsartan, titrated to target dose based on systolic blood pressure during hospitalization, had the same beneficial effect on the primary and safety endpoints in ACEI/ARB-naive patients.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In summary, the TRANSITION and PIONEER-HF results provide complementary data to PARADIGM-HF, addressing previous gaps in evidence. They support the use of sacubitril/valsartan both during hospital stay and in outpatient settings. Although there are still a few unanswered questions and unpublished results from both trials, the data from PIONEER-HF and TRANSITION support the in-hospital initiation of sacubitril/valsartan in all NYHA II-III patients early after stabilization, and independently of prior HF diagnosis or ACEI/ARB exposure. There are now grounds for initiating therapy in HFrEF with ACEI safely as a first option, in both in-hospital and outpatient settings.</p><p id="par0045" class="elsevierStylePara elsevierViewall">On the basis of this new information, our paper “Sacubitril/valsartan: a practical guide” should be revisited as in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">Cândida Fonseca has received fees from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Novartis, Orion, Roche, Servier and Vifor (companies that develop and market tests and/or treatments in the area of HF) for HF consulting, sitting on clinical study steering committees and giving lectures at congresses and other scientific sessions. Dulce Brito has received fees from Novartis, Orion, Roche, Servier, St. Jude and Vifor (companies that develop and market tests and/or treatments in the area of HF) for HF consulting, and has given talks at congresses and other scientific sessions. She also reports consultancy and research fellowships from Genzyme-Sanofi and consultancy and lecture fees from Pfizer, and has attended meetings sponsored by Shire Human Genetic Therapies (companies that develop and market treatments in the area of cardiomyopathies). Jorge Ferreira has received consulting and speaker fees from Amgen, AstraZeneca, Boehringer-Ingelheim, MerckSharp & Dohme, Novartis, and Orion. Fátima Franco has received consulting and speaker fees from Novartis. João Morais received honoraria within the last two years from pharmaceutical companies for consulting activities (Bayer Healthcare, Astra Zeneca, Merck Sharp & Dhome, Novartis) and fees for lectures (Boehringer Ingelheim, Bial, Servier, Daiichi Sankyo, Boston Scientific). He is also National Coordinator for the PARADISE-MI trial on sacubitril/valsartan in patients with myocardial infarction. José Silva Cardoso was national coordinator of the PARADIGM-HF study and was a consultant for Novartis, AstraZeneca Pharmaceuticals, Orion, Pfizer, Servier and Vifor (companies that develop and market treatments for HF). He has sat on steering committees for clinical studies sponsored by Novartis, Orion and Pfizer and has received honoraria as a speaker in sessions on HF and research fellowships from Novartis, Abbott, AstraZeneca Pharmaceuticals, Bial, Boehringer Ingelheim, Menarini, Merck Serono, Merck Sharp & Dohme, Orion, Pfizer, Sanofi, Servier and Vifor.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">IN WHOM AND WHEN?</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Indications:</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>• Adult patients with heart failure and reduced ejection fraction (LVEF <40%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>• Replacement of ACEI/ARB in outpatients who remain in NYHA class II-IV despite treatment with an ACEI/ARB, a beta-blocker and an MRA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>• Before discharge, in stabilized patients admitted with a primary diagnosis of decompensated or de novo acute heart failure, irrespective of prior ACEI/ARB exposure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>• Patients should have SBP ≥100 mmHg and serum potassium level <5.5 mmol/l. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Suggested revision of Table 1 in Sacubitril/valsartan: a practical guide.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a></p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sacubitril/valsartan: a practical guide" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. 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Senni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ehf2.12246" "Revista" => array:6 [ "tituloSerie" => "ESC Heart Fail" "fecha" => "2018" "volumen" => "5" "paginaInicial" => "327" "paginaFinal" => "336" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29239515" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0080" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.P. Maggioni" 1 => "S.D. Anker" 2 => "U. Dahlstrom" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurjhf/hft134" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "1173" "paginaFinal" => "1184" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23978433" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0085" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E.J. Velazquez" 1 => "D.A. Morrow" 2 => "A.D. DeVore" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2018.01.004" "Revista" => array:6 [ "tituloSerie" => "Am Heart J" "fecha" => "2018" "volumen" => "198" "paginaInicial" => "145" "paginaFinal" => "151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29653636" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0090" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prior exposure to a conventional renin-angiotensin system antagonist and angiotensin receptor-neprilysin inhibition in acute decompensated heart failure: a prespecified subgroup analysis of the PIONEER-HF trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.P. Ambrosy" 1 => "A. DeVore" 2 => "D. Morrow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:3 [ "titulo" => "Presented at ACC19 (American College of Cardiology annual meeting)" "conferencia" => "New Orleans, Louisiana, March 16-18, 2019" "serieFecha" => "2019" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000003800000007/v6_201912041744/S0870255119304597/v6_201912041744/en/main.assets" "Apartado" => array:4 [ "identificador" => "55963" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Carta ao Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000003800000007/v6_201912041744/S0870255119304597/v6_201912041744/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255119304597?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 8 | 9 | 17 |
| 2024 Outubro | 67 | 54 | 121 |
| 2024 Setembro | 76 | 52 | 128 |
| 2024 Agosto | 64 | 47 | 111 |
| 2024 Julho | 64 | 34 | 98 |
| 2024 Junho | 66 | 50 | 116 |
| 2024 Maio | 64 | 29 | 93 |
| 2024 Abril | 75 | 45 | 120 |
| 2024 Maro | 55 | 30 | 85 |
| 2024 Fevereiro | 41 | 29 | 70 |
| 2024 Janeiro | 45 | 19 | 64 |
| 2023 Dezembro | 66 | 27 | 93 |
| 2023 Novembro | 47 | 42 | 89 |
| 2023 Outubro | 38 | 23 | 61 |
| 2023 Setembro | 36 | 35 | 71 |
| 2023 Agosto | 36 | 18 | 54 |
| 2023 Julho | 45 | 25 | 70 |
| 2023 Junho | 74 | 24 | 98 |
| 2023 Maio | 69 | 34 | 103 |
| 2023 Abril | 50 | 22 | 72 |
| 2023 Maro | 71 | 28 | 99 |
| 2023 Fevereiro | 49 | 26 | 75 |
| 2023 Janeiro | 33 | 23 | 56 |
| 2022 Dezembro | 57 | 33 | 90 |
| 2022 Novembro | 45 | 29 | 74 |
| 2022 Outubro | 70 | 27 | 97 |
| 2022 Setembro | 54 | 47 | 101 |
| 2022 Agosto | 53 | 41 | 94 |
| 2022 Julho | 52 | 56 | 108 |
| 2022 Junho | 64 | 62 | 126 |
| 2022 Maio | 41 | 43 | 84 |
| 2022 Abril | 46 | 45 | 91 |
| 2022 Maro | 49 | 51 | 100 |
| 2022 Fevereiro | 46 | 49 | 95 |
| 2022 Janeiro | 58 | 57 | 115 |
| 2021 Dezembro | 48 | 42 | 90 |
| 2021 Novembro | 42 | 55 | 97 |
| 2021 Outubro | 57 | 59 | 116 |
| 2021 Setembro | 73 | 35 | 108 |
| 2021 Agosto | 38 | 46 | 84 |
| 2021 Julho | 38 | 30 | 68 |
| 2021 Junho | 38 | 30 | 68 |
| 2021 Maio | 57 | 55 | 112 |
| 2021 Abril | 93 | 44 | 137 |
| 2021 Maro | 112 | 54 | 166 |
| 2021 Fevereiro | 48 | 30 | 78 |
| 2021 Janeiro | 59 | 33 | 92 |
| 2020 Dezembro | 34 | 37 | 71 |
| 2020 Novembro | 64 | 36 | 100 |
| 2020 Outubro | 60 | 23 | 83 |
| 2020 Setembro | 75 | 24 | 99 |
| 2020 Agosto | 27 | 24 | 51 |
| 2020 Julho | 50 | 29 | 79 |
| 2020 Junho | 55 | 47 | 102 |
| 2020 Maio | 42 | 32 | 74 |
| 2020 Abril | 22 | 27 | 49 |
| 2020 Maro | 39 | 27 | 66 |
| 2020 Fevereiro | 110 | 106 | 216 |
| 2020 Janeiro | 35 | 41 | 76 |
| 2019 Dezembro | 43 | 30 | 73 |
| 2019 Novembro | 80 | 44 | 124 |
| 2019 Outubro | 101 | 45 | 146 |
| 2019 Setembro | 56 | 61 | 117 |
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