Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC WcLXD4ccHKND66j8xxqrCSn S0066-782X2022005005203 S0066-782X2022000601018 abc.20210328 10.36660/abc.20210328 Artigo Original Alcance das Metas de Colesterol LDL após Infarto Agudo do Miocárdio: Dados Reais do Sistema Público de Saúde da Cidade de Curitiba 0000-0003-4972-5005 Bernardi André 1 2 Olandoski Marcia 1 Erbano Lucas Olandoski 1 Guarita-Souza Luiz Cesar 1 Baena Cristina Pellegrino 1 0000-0002-1397-0634 Faria-Neto José Rocha 1 Faculdade de Medicina Pontifícia Universidade Católica do Paraná Curitiba PR Brasil Faculdade de Medicina, Pontifícia Universidade Católica do Paraná, Curitiba, PR – Brasil Hospital Universitário Evangélico Mackenzie Curitiba PR Brasil Hospital Universitário Evangélico Mackenzie, Curitiba, PR – Brasil Correspondência: André Bernardi • Rua Eduardo Sprada, 630. CEP 81.220-000, Curitiba, PR - Brasil E-mail: bernardiandre@hotmail.com

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 09 05 2022 2022 118 6 1018 1025 13 04 2021 18 08 2021 01 09 2021 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Resumo Fundamento

A redução dos níveis de colesterol LDL é a pedra angular na redução de risco, mas muitos pacientes de alto risco não estão atingindo as metas lipídicas recomendadas, mesmo em países de alta renda.

 Objetivo

Avaliar se os pacientes atendidos na rede pública de saúde da cidade de Curitiba estão atingindo as metas de colesterol LDL após infarto agudo do miocárdio (IAM).

 Métodos

Esta coorte retrospectiva explorou os dados de pacientes internados com IAM entre 2008 e 2015 em hospitais públicos da cidade de Curitiba. Para avaliar o atingimento da meta de colesterol LDL, utilizamos o último valor registrado no banco de dados para cada paciente até o ano de 2016. Para aqueles que tinham pelo menos um valor de colesterol LDL registrado no ano anterior ao IAM, calculou-se o percentual de redução. O nível de significância adotado para a análise estatística foi p<0,05.

 Resultados

Dos 7.066 pacientes internados por IAM, 1.451 foram acompanhados em ambiente ambulatorial e tiveram pelo menos uma avaliação de colesterol LDL. A média de idade foi 60,8±11,4 anos e 35,8%, 35,2%, 21,5% e 7,4% dos pacientes apresentavam níveis de colesterol LDL≥100, 70–99, 50–69 e <50 mg/dL, respectivamente. Destes, 377 pacientes também tiveram pelo menos uma avaliação de colesterol LDL antes do IAM. As concentrações médias de colesterol LDL foram 128,0 e 92,2 mg/dL antes e após o IAM, com redução média de 24,3% (35,7 mg/dL). Os níveis de colesterol LDL foram reduzidos em mais de 50% em apenas 18,3% dos casos.

 Conclusão

Na cidade de Curitiba, pacientes do sistema público de saúde, após infarto do miocárdio, não estão atingindo níveis adequados de colesterol LDL após IAM.

 Doenças Cardiovaculares Infarto do Miocárdio Dislipidemias Prevenção Secundária Diabetes Mellitus Colesterol LDL Epidemiologia Prevenção e Controle Fatores de Risco Introdução

As doenças cardiovasculares (DCVs) são a principal causa de óbito no Brasil e no mundo. Globalmente, reportou-se uma estimativa de cerca de 18 milhões de óbitos por DCV em 2017, 85% das quais foram atribuídas a doenças isquêmicas do coração e cerebrovasculares.1 De acordo com as Estatísticas Cardiovasculares - Brasil, aproximadamente 388.268 pessoas morreram de DCV no país.2 Embora a taxa de mortalidade por doença isquêmica do coração (DIC) tenha permanecido estável na década de 2000,3 dados atuais mostram que a taxa de mortalidade por DIC padronizada por idade tem diminuído no Brasil.2

Níveis plasmáticos elevados de colesterol LDL (lipoproteína de baixa densidade) estão intimamente relacionados com o aumento do risco cardiovascular, independentemente da faixa etária.4 Além disso, a redução do colesterol LDL está associada à redução do risco cardiovascular: uma redução de 39 mg/dL está associada a uma redução de aproximadamente 20% no risco de eventos cardiovasculares maiores,5 um efeito semelhante entre os sexos.6 Em pacientes com alto risco de eventos cardiovasculares, principalmente aqueles com doença coronariana estabelecida, grandes reduções no Colesterol LDL com maiores doses de estatinas têm mostrado resultados melhores do que aquelas com doses inferiores.7,8 Da mesma forma, reduções adicionais no colesterol LDL, por meio do emprego de terapias adicionais combinadas com estatinas em pacientes de alto risco nas doses máximas otimizadas também estão associadas a reduções adicionais em novos eventos.9,10

Embora não se tenha identificado um nível mínimo ideal de colesterol LDL, sem risco de DCVs, os consensos e diretrizes atuais buscam estabelecer metas lipídicas para orientar o atendimento médico individualizado.11-13 Essas metas podem ser expressas como valores-alvo absolutos de colesterol LDL ou como porcentagens mínimas de redução do colesterol LDL. No entanto, muitos pacientes de alto risco não estão atingindo as metas lipídicas recomendadas,14 mesmo sob terapia hipolipemiante.15 Este é um problema multifatorial que requer quantificação em contextos locais específicos para garantir a viabilidade local e a eficácia das soluções propostas.16 No Brasil, embora a saúde seja considerada um dever do Estado, o acesso a estatinas mais potentes é limitado no Sistema Único de Saúde (SUS), sistema público de saúde brasileiro que atende mais de 70% da população.17

Até o momento, alguns estudos de mundo real foram conduzidos no Brasil, mostrando que pacientes com risco cardiovascular estão atingindo as metas lipídicas recomendadas.18,19 O objetivo deste estudo foi determinar a porcentagem de pacientes no sistema público de saúde da cidade de Curitiba, Brasil, que atingiram as metas de colesterol LDL após internação por infarto agudo do miocárdio (IAM), incluindo tanto o alcance dos valores-alvo de colesterol LDL quanto o percentual de redução do colesterol LDL em relação aos níveis anteriores ao IAM.

 Métodos

Trata-se de um estudo de coorte retrospectivo realizado no banco de dados da Secretaria Municipal de Saúde (SMS) de Curitiba, contendo todas as informações dos pacientes internados na rede pública municipal de saúde, desde a entrada até a alta. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa (CEP) da SMS e pela instituição acadêmica envolvida.

A coorte de pacientes selecionada no banco de dados incluiu pacientes de ambos os sexos com 18 anos ou mais, internados em um hospital público da rede de saúde local com diagnóstico primário de IAM (código CID-I21) entre janeiro de 2008 e dezembro de 2015. Os resultados dos exames laboratoriais foram obtidos a partir de um segundo banco de dados e as identidades dos pacientes foram verificadas minuciosamente para evitar duplicação e discrepâncias. Casos duplicados e casos com discrepâncias foram excluídos. Pacientes sem pelo menos um valor de colesterol LDL registrado no ano seguinte ao IAM também foram excluídos. Realizou-se uma busca no banco de dados do laboratório para encontrar os pacientes (entre os pacientes incluídos, ou seja, aqueles com pelo menos um exame após o IAM) que também haviam feito pelo menos um exame de colesterol LDL no ano anterior ao IAM para calcular o percentual de redução.

Avaliação do colesterol LDL

Com base na fórmula de Friedewald, obteve-se o último valor de colesterol LDL, registrado na base de dados após o IAM, ou seja, o mais distante da data do IAM, exceto para pacientes com triglicerídeos acima de 400 mg/dL. Foram determinadas as porcentagens de pacientes que alcançaram níveis médios de colesterol LDL <50, 50–69, 70–99 ou ≥100 mg/dL.

Para determinar o percentual de redução alcançado, pesquisou-se o banco de dados em busca de pacientes com pelo menos um exame de colesterol LDL no ano anterior ao IAM. Nos casos de pacientes com mais de um exame, utilizou-se o valor de colesterol LDL mais próximo ao evento agudo. O valor de colesterol LDL mais próximo ao IAM no ano anterior ao evento foi comparado ao último valor obtido após o IAM. As porcentagens de pacientes que alcançaram reduções do colesterol LDL de 50–100% ou <50% ou aumentos <50% ou 50–100% também foram determinadas.

 Análise Estatística

Realizou-se a análise estatística descritiva dos dados. Os resultados foram expressos como médias e desvios-padrão (variáveis quantitativas) ou como frequências e porcentagens (variáveis categóricas). Utilizou-se o teste t de Student pareado para comparar o colesterol LDL antes e depois do IAM. A normalidade dos dados foi analisada pelo teste de Kolmogorov-Smirnov. Definiu-se a significância estatística com p<0,05. Os dados foram analisados com o programa computacional IBM SPSS Statistics v.20.0. Armonk, NY: IBM Corp.

 Resultados

Do total de 7.066 pacientes internados por IAM entre janeiro de 2008 e dezembro de 2015, 61 foram excluídos devido a pelo menos um dos critérios de exclusão (duplicação ou discrepância entre as datas de internação). Dos 7.005 casos restantes, 5.554 foram excluídos por falta de resultados do exame de colesterol LDL após o IAM. Portanto, avaliou-se o colesterol LDL após o IAM em 1.451 casos (Figura 1). Destes, 377 pacientes também realizaram pelo menos um exame no ano anterior ao IAM, o que permitiu o cálculo da variação percentual.

– Fluxograma das características da amostra do estudo. IAM: Infarto agudo do miocárdio; colesterol LDL: Colesterol LDL (lipoproteína de baixa densidade).

A média de idade dos 1.451 pacientes foi 60,8±11,4. A Tabela 1 mostra a média e o desvio padrão (DP) do colesterol LDL entre os 1.451 casos após o IAM. O tempo médio até o último exame de colesterol LDL realizado após o IAM foi de 32,7 meses. A Figura 2 mostra as porcentagens dos níveis de colesterol LDL dos pacientes. Assim, apenas 28,9% dos pacientes apresentaram níveis de colesterol LDL <70 mg/dL após IAM.

– Média e desvio padrão do colesterol LDL, colesterol HDL, colesterol total e triglicerídeos entre os 1.451 casos após o infarto agudo do miocárdio
Média DP
Colesterol LDL (mg/dL) 93,3 34,2
Colesterol HDL (mg/dL) 42,9 11,6
Colesterol total (mg/dL) 168,1 39,8

LDL: lipoproteína de baixa densidade; HDL: lipoproteína de alta densidade; DP: desvio padrão.

– Distribuição dos níveis de colesterol LDL (n=1.451). LDL-C: colesterol lipoproteína de baixa densidade.

Os valores de colesterol LDL após IAM, entre os 377 pacientes com dados de colesterol LDL no ano anterior ao IAM e pelo menos um exame de colesterol LDL após o evento, foram os seguintes: na mesma faixa de antes (40,3%), em uma faixa menor do que antes (53,3%), e em uma faixa maior do que antes (6,4%) (Tabela 2). O tempo médio entre os exames de colesterol LDL antes e o mais próximo ao IAM e ao evento em si foi de 4,8 meses. As concentrações médias de colesterol LDL (Figura 3) foram 128,0 e 92,2 mg/dL antes e após o IAM, respectivamente (Tabela 3). A Figura 4 mostra que 19,3% dos pacientes tiveram uma redução de mais de 50% nos níveis de colesterol LDL após o IAM. Além disso, aproximadamente 82% dos pacientes alcançaram algum grau de redução do colesterol LDL (Figura 4).

– Distribuição dos níveis de colesterol LDL antes e depois do infarto agudo do miocárdio
Colesterol LDL após IAM (mg/dL) Colesterol LDL antes do IAM (mg/dL) Total
<50 50–69 70–99 ≥100
<50 1 6 8 11 26
0,3% 1,6% 2,1% 2,9%
50–69 2 6 29 56 93
0,5% 1,6% 7,7% 14,6%
70–99 2 4 31 93 130
0,5% 1,3% 8,2% 24,4%
≥100 0 0 13 115 128
0,0% 0,0% 3,7% 30,2%
Total 6 17 82 272 377

LDL: lipoproteína de baixa densidade; IAM: infarto agudo do miocárdio.

– Box-plot do colesterol LDL antes e depois do infarto agudo do miocárdio. Teste t de Student: p<0.05. IAM: Infarto agudo do miocárdio; colesterol LDL: Colesterol LDL (lipoproteína de baixa densidade).

– Média e diminuição do colesterol de lipoproteína de baixa densidade antes e depois do infarto agudo do miocárdio entre os 377 casos
Variável Média DP p*
Antes do IAM (mg/dL) 128,0 42,7 <0,001
Após IAM (mg/dL) 92,2 36,9
Redução (absoluta) (mg/dL) 35,7 40,1
Redução (relativa) (%) 24,3% 28,4%

*Teste t de Student pareado, p<0,05. IAM: infarto agudo do miocárdio; DP: desvio padrão.

– Distribuição dos pacientes de acordo com a alteração no colesterol LDL antes e depois do infarto agudo do miocárdio. LDL: Colesterol LDL (lipoproteína de baixa densidade).

Discussão

Apesar da eficácia da diminuição nas taxas de lipídios na redução de eventos cardiovasculares, muitos pacientes de alto risco não estão atingindo a meta lipídica recomendada. Este novo estudo realizado com dados de pacientes com IAM internados no sistema público de saúde de Curitiba constatou que aproximadamente 82% dos pacientes alcançaram algum grau de redução do colesterol LDL, com apenas aproximadamente 30% atingindo níveis médios <70 mg/dL e aproximadamente 20% tendo uma redução >50% em comparação com os níveis anteriores ao IAM.

Os resultados deste estudo são semelhantes aos conduzidos em contextos socioeconômicos muito diferentes. Dados recentes de 27 países europeus mostraram que, entre 8.261 pacientes coronarianos incluídos no estudo EUROASPIRE V, 80% estavam tomando estatinas e 71% tinham concentrações de colesterol LDL ≥70 mg/dL.15 Em um estudo americano mais antigo, que também avaliou pacientes após síndrome coronariana aguda (SCA) por meio da avaliação do controle lipídico no primeiro ano após o evento, apenas 31% dos pacientes atingiram o nível alvo de colesterol LDL <70 mg/dL.20 Os dados obtidos neste estudo são alarmantes por se tratarem de pacientes com pós-SCA, uma população de alto risco para novos eventos cardiovasculares a curto e médio prazo. O registro GRACE mostrou que aproximadamente 10% dos pacientes que receberam alta após SCA sofrerão IAM não fatal ou morte relacionada ao sistema cardiovascular em seis meses.21 Uma subanálise mais recente de pacientes com IAM prévio incluídos no estudo FOURIER demonstrou que um IAM mais recente apresenta maior risco de um novo evento cardiovascular do que um IAM mais distante (mais de dois anos) e esses pacientes são justamente aqueles que se beneficiam de uma redução lipídica mais agressiva.22

As metas propostas para os níveis de colesterol LDL foram extrapoladas a partir dos resultados de estudos com doses fixas de estatinas porque o primeiro estudo visando uma meta específica de colesterol LDL de 25–50 mg/dL foi conduzido apenas recentemente.23 Portanto, em 2013, a American Heart Association e o American College of Cardiology pararam de recomendar uma meta específica de colesterol LDL e propuseram o tratamento de pacientes de alto risco com altas doses de estatinas potentes capazes de reduzir o colesterol LDL em >50% com base nos resultados estudos intervencionais randomizados conduzidos nessas populações.24 Um estudo clínico que comparou estratégias para reduzir o risco cardiovascular (nível atingido ou porcentagem de redução) para determinar qual é o mais eficaz ainda não foi realizado, mas uma análise de dados de 13.937 pacientes dos três estudos distintos sobre prevenção secundária com estatinas sugere que uma redução de >50% reduziria o risco incrementalmente, mesmo em pacientes com níveis de colesterol LDL <70 mg/dL.25

Na presente amostra, mais pacientes alcançaram níveis de colesterol LDL <70 mg/dL do que aqueles que alcançaram uma redução de >50%. Isso pode ser explicado pelo fato de o percentual de redução estar diretamente associado ao uso de altas doses de estatinas potentes. O acesso a esses medicamentos no sistema público de saúde brasileiro é restrito e a indisponibilidade desses medicamentos neste sistema é uma barreira reconhecida ao seu uso.26 Há relatos de menor uso de medicamentos necessários para a prevenção secundária em países de baixa renda. Por exemplo, o estudo PURE relatou 66,5% e 3,3% do uso de estatinas para prevenção secundária em países de alta e baixa renda, respectivamente.27

Na época em que este estudo foi realizado, a 5ª Diretriz Brasileira de Dislipidemia e Prevenção da Aterosclerose28 recomendava metas de colesterol LDL abaixo de 70 mg/dL para pacientes com alto risco cardiovascular. Além disso, a recomendação para reduzir o colesterol LDL em pelo menos 50% aparece apenas na diretriz brasileira de 2017.11 As evidências atuais indicam que o benefício clínico não depende do tipo de estatina usada, mas sim da extensão da redução do colesterol LDL. Mais importante ainda é avaliar o risco cardiovascular do paciente e iniciar o tratamento visando a redução adequada do risco. Para pessoas de risco muito alto, uma meta de colesterol LDL de <55 mg/dL e uma redução de ≥50% do colesterol LDL basal deve ser alcançada.13

A American Association of Clinical Endocrinologists e o American College of Endocrinology propuseram uma meta de colesterol LDL de <55 mg/dL para uma nova categoria de risco denominada “risco extremo”.29 Esta categoria se refere a pacientes com doença cardiovascular aterosclerótica progressiva (DCAP), incluindo angina instável que persista mesmo após o alcance de um colesterol LDL de <70 mg/dL, ou DCAP clinicamente estável com diabetes, doença renal crônica estágio 3 ou 4 e/ou hipercolesterolemia familiar heterozigótica, ou pacientes com histórico de DCAP prematura (<55 anos de idade para homens ou <65 anos de idade para mulheres). Neste estudo, apenas 7,4% dos pacientes atingiram níveis inferiores a 50 mg/dL após IAM.

Embora as diretrizes americanas recomendem a redução dos níveis de colesterol LDL em pelo menos 50% do nível basal em pacientes coronarianos,30 as diretrizes europeias propõem uma meta de colesterol LDL de <55 mg/dL e uma redução mínima de 50% no colesterol LDL em pacientes com doença arterial coronariana (DAC) documentada.13 As diretrizes americanas e europeias recomendam o tratamento com uma combinação de medicamentos hipolipemiantes para atingir essas metas. No entanto, a diretriz americana concorda que o foco é a redução do colesterol LDL, principalmente com base em uma redução de >50% do valor basal, em vez de atingir os níveis-alvo específicos de colesterol LDL. No entanto, é importante destacar que os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) e a ezetimiba são aceitáveis em pacientes com IAM considerado de risco muito alto e com colesterol LDL ≥70 mg/dL em estatina com tolerância máxima.

Os resultados do estudo IMPROVE-IT mostraram que um número significativamente maior de pacientes com DAC tratados com estatina e ezetimiba alcançaram as metas de colesterol LDL em comparação com estatinas de maneira isolada.31

Limitações do Estudo

Esta análise tem várias limitações possíveis. Apenas uma minoria dos pacientes internados com IAM na rede pública de saúde de Curitiba realizou exame de colesterol no ano seguinte ao IAM. Muitos pacientes que receberam tratamento em Curitiba provavelmente não eram da cidade. Portanto, a perda de seguimento ambulatorial foi significativa, pois esses pacientes retornaram às suas cidades de origem para acompanhamento médico e cuidados de prevenção secundária ou até mesmo interromperam o acompanhamento. Não foram obtidos dados sobre o colesterol LDL de pacientes que não receberam seguimento ambulatorial na rede pública de saúde de Curitiba. No entanto, a coorte de análise foi representativa de uma população real de Curitiba com infarto do miocárdio que sobreviveu à hospitalização. Por fim, a maior limitação deste estudo foi a ausência de dados sociodemográficos e medicamentosos, seja quanto ao uso (ou não) de estatinas, seja quanto às doses administradas antes e após o IAM.

 Conclusão

Após o IAM, uma minoria de pacientes de alto risco cardiovascular atingiu as metas de colesterol LDL recomendadas nesta coorte de pacientes internados no sistema público de saúde da cidade de Curitiba. A semelhança entre os resultados deste estudo e os de estudos realizados em países com condições socioeconômicas muito diferentes sugere que outros fatores, provavelmente relacionados aos próprios médicos e pacientes, podem estar associados a esse cenário.

Concepção e desenho da pesquisa: Bernardi A, Erbano LO, Guarita-Souza LC, Baena CP, Faria-Neto JR; Obtenção de dados: Bernardi A, Erbano LO; Análise e interpretação dos dados e Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Bernardi A, Olandoski M, Guarita-Souza LC, Baena CP, Faria-Neto JR; Análise estatística: Olandoski M, Erbano LO, Faria-Neto JR; Redação do manuscrito: Bernardi A, Faria-Neto JR.

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Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015;385:1397-405. Cholesterol Treatment Trialists C Fulcher J O’Connell R et al Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials Lancet 2015 385 1397 1405 7. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al.et al. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. N Engl J Med.2005;352(14):1425-35. doi: 10.1056/NEJMoa050461. LaRosa JC Grundy SM Waters DD Shear C Barter P Fruchart JC et al.et al Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease N Engl J Med 2005 352 14 1425 1435 10.1056/NEJMoa050461. 8. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. New England Journal of Medicine 2004;350:(14)1495-504. Cannon CP Braunwald E McCabe CH Rader DJ Rouleau JL Belder R et al Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes New England Journal of Medicine 2004 350 14 1495 1504 9. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(15):2387-97. doi: 10.1056/NEJMoa040583. Cannon CP Blazing MA Giugliano RP et al Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes N Engl J Med 2015 372 15 2387 2397 10.1056/NEJMoa040583. 10. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-22. doi: 10.1056/NEJMoa1615664 Sabatine MS Giugliano RP Keech AC et al Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease N Engl J Med 2017 376 18 1713 1722 10.1056/NEJMoa1615664 11. Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune A Neto, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose – 2017. Arq Bras Cardiol. 2017 Jul;109(2 Supl 1):1-76. doi: 10.5935/abc.20170121. Faludi AA Izar MCO Saraiva JFK Chacra APM Bianco HT Afiune A Neto et al Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose – 2017 Arq Bras Cardiol 2017 07 109 2 Supl 1 1 76 10.5935/abc.20170121. 12. Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, De Palma AS, et al. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways . J Am Coll Cardiol.2017;70(14):1785-822. Lloyd-Jones DM Morris PB Ballantyne CM Birtcher KK Daly DD Jr De Palma AS et al 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways J Am Coll Cardiol 2017 70 14 1785 1822 13. Mach F, Baigent C, Catapano AL, Koskinas KC. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2019;41(1):111-88. doi: 10.1093/eurheartj/ehz455. Mach F Baigent C Catapano AL Koskinas KC 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk Eur Heart J 2019 41 1 111 188 10.1093/eurheartj/ehz455. 14. Waters DD, Brotons C, Chiang CW, Ferrieres J, Foody J, Wouter J, et al. Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation 2009;120(1):28-34. 10.1161/CIRCULATIONAHA.108.838466 Waters DD Brotons C Chiang CW Ferrieres J Foody J Wouter J et al Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals Circulation 2009 120 1 28 34 10.1161/CIRCULATIONAHA.108.838466 15. Kotseva K, De Backer G, De Bacquer D, Ryden L, Hoes A, Grobbee D, et al. Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry. Eur J Prev Cardiol. 2019;26(8):824-35. doi: 10.1177/2047487318825350. Kotseva K De Backer G De Bacquer D Ryden L Hoes A Grobbee D et al Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry Eur J Prev Cardiol 2019 26 8 824 835 10.1177/2047487318825350. 16. Murphy A, Faria-Neto JR, Al-Rasadi K, Blom D, Catapano A, Cuevas A, et al World Heart Federation Cholesterol Roadmap. Glob Heart. 2017;12(3):179-97 e5. doi: 10.1016/j.gheart.2017.03.002. Murphy A Faria JR Neto Al-Rasadi K Blom D Catapano A Cuevas A et al World Heart Federation Cholesterol Roadmap Glob Heart 2017 12 3 179 97 e5 10.1016/j.gheart.2017.03.002. 17. Massuda A, Hone T, Leles FAG, de Castro MC, Atun R. The Brazilian health system at crossroads: progress, crisis and resilience. BMJ Glob Health 2018;3(4):e000829. doi: 10.1136/bmjgh-2018-000829. MassudaAHoneTLelesFAGde CastroMCAtunRThe Brazilian health system at crossroads: progress, crisis and resilienceBMJ Glob Health201834e00082910.1136/bmjgh-2018-000829. 18. Waters DD, Brotons C, Chiang CW, Ferrières J, Foody J, Jukema JW, Santos RD, et al. Lipid Treatment Assessment Project 2 Investigators. Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation. 2009 Jul 7;120(1):28-34. doi: 10.1161/CIRCULATIONAHA.108.838466. Waters DD Brotons C Chiang CW Ferrières J Foody J Jukema JW Santos RD et al Lipid Treatment Assessment Project 2 Investigators. Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals Circulation 2009 07 7 120 1 28 34 10.1161/CIRCULATIONAHA.108.838466. 19. Lotufo PA, Santos RD, Figueiredo RM, Pereira AC, Mill JG, Alvim SM, Fonseca MJ, Almeida MC, Molina MC, Chor D, Schmidt MI, Ribeiro AL, Duncan BB, Bensenor IM. Prevalence, awareness, treatment, and control of high low-density lipoprotein cholesterol in Brazil: Baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). J Clin Lipidol. 2016 May-Jun;10(3):568-76. doi: 10.1016/j.jacl.2015.12.029. Lotufo PA Santos RD Figueiredo RM Pereira AC Mill JG Alvim SM Fonseca MJ Almeida MC Molina MC Chor D Schmidt MI Ribeiro AL Duncan BB Bensenor IM Prevalence, awareness, treatment, and control of high low-density lipoprotein cholesterol in Brazil: Baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) J Clin Lipidol 2016 May-Jun 10 3 568 576 10.1016/j.jacl.2015.12.029 20. Melloni C, Shah BR, Ou FS, Roe MT, Smith SC Jr, Pollack CV Jr, et al. Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry. Am Heart J 2010;160:1121-9, 9 e1. doi: 10.1016/j.ahj.2010.09.008. Melloni C Shah BR Ou FS Roe MT Smith SC Jr Pollack CV Jr et al Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry Am Heart J 2010 160 1121 1129 9 e1 10.1016/j.ahj.2010.09.008 21. Fox KAA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Vander Werf F, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 2006;333(7578):1091. doi: 10.1136/bmj.38985.646481.55. Fox KAA Dabbous OH Goldberg RJ Pieper KS Eagle KA Vander Werf F et al Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE) BMJ 2006 333 7578 1091 10.1136/bmj.38985.646481.55 22. Sabatine MS, De Ferrari GM, Giugliano RP, Huber K, Lewis BS, Ferreira J, et al. Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: An Analysis from FOURIER. Circulation 2018;138(8):756-66. doi: 10.1161/CIRCULATIONAHA.118.034309. Sabatine MS De Ferrari GM Giugliano RP Huber K Lewis BS Ferreira J et al Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: An Analysis from FOURIER Circulation 2018 138 8 756 766 10.1161/CIRCULATIONAHA.118.034309 23. Schwartz GG, Bessac L, Berdan LG, Bhatt DL, Bittner V, Diaz R, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J 2014;168(5):682-9. doi: 10.1016/j.ahj.2014.07.028. Schwartz GG Bessac L Berdan LG Bhatt DL Bittner V Diaz R et al Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial Am Heart J 2014 168 5 682 689 10.1016/j.ahj.2014.07.028 24. Stone NJ, Robinson JG, Lichtenstein AH, Bairdy Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(25 Pt B):2889-934. doi: 10.1016/j.jacc.2013.11.002. Stone NJ Robinson JG Lichtenstein AH Bairdy Merz CN Blum CB Eckel RH et al 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2014 63 25 Pt B 2889 2934 10.1016/j.jacc.2013.11.002 25. Bangalore S, Fayyad R, Kastelein JJ, Laskey R, Amarenco P, De Micco DA, et al. 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis? Am J Med 2016;129(4):384-91. DOI: 10.1016/j.amjmed.2015.10.024 Bangalore S Fayyad R Kastelein JJ Laskey R Amarenco P De Micco DA et al 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis? Am J Med 2016 129 4 384 391 10.1016/j.amjmed.2015.10.024 26. Banerjee A, Khandelwal S, Nambiar L, Saxena M, Peck V, Moniruzza M, et al. Health system barriers and facilitators to medication adherence for the secondary prevention of cardiovascular disease: a systematic review. Open Heart 2016;3(2):e000438. doi: 10.1136/openhrt-2016-000438. Banerjee A Khandelwal S Nambiar L Saxena M Peck V Moniruzza M et al Health system barriers and facilitators to medication adherence for the secondary prevention of cardiovascular disease: a systematic review Open Heart 2016 3 2 e000438 10.1136/openhrt-2016-000438 27. Yusuf S, Islam S, Chow CK, Rangarajavan S, Dagemais G, Diaz R, et al. et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey. The Lancet 2011;378(9798):1231-43. doi: 10.1016/S0140-6736(11)61215-4. Yusuf S Islam S Chow CK Rangarajavan S Dagemais G Diaz R et al et al Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey The Lancet 2011 378 9798 1231 1243 10.1016/S0140-6736(11)61215-4 28. Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, et al. et al. V Diretriz Brasileira de Dislipidemia e Prevenção da Aterosclerose. Arq Bras Cardiol. 2013 101(4 Supl1):1-22. DOI: 10.5935/abc.2013S010 Xavier HT Izar MC Faria JR Neto Assad MH Rocha VZ Sposito AC et al et al V Diretriz Brasileira de Dislipidemia e Prevenção da Aterosclerose Arq Bras Cardiol 2013 101 4 Supl1 1 22 10.5935/abc.2013S010 29. Jellinger PS. American Association of Clinical Endocrinologists/American College of Endocrinology Management of Dyslipidemia and Prevention of Cardiovascular Disease Clinical Practice Guidelines. Diabetes Spectr 2018;31(3):234-45. doi: 10.2337/ds18-0009. Jellinger PS American Association of Clinical Endocrinologists/American College of Endocrinology Management of Dyslipidemia and Prevention of Cardiovascular Disease Clinical Practice Guidelines Diabetes Spectr 2018 31 3 234 245 10.2337/ds18-0009 30. Grundy SM, Stone NJ, Bailey AL, Bam C, Birtcher KK, Blumenthall RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139(25):e1082-e1143. doi: 10.1161/CIR.0000000000000625 Grundy SM Stone NJ Bailey AL Bam C Birtcher KK Blumenthall RS et al 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines Circulation 2019 139 25 e1082 e1143 10.1161/CIR.0000000000000625 31. Bohula EA, Giugliano RP, Cannon CP, Zhou J, Murphy AS, White JÁ, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015;132(13):1224-33. doi: 10.1161/CIRCULATIONAHA.115.018381. Bohula EA Giugliano RP Cannon CP Zhou J Murphy AS White JÁ et al Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT Circulation 2015 132 13 1224 1233 10.1161/CIRCULATIONAHA.115.018381

Fontes de financiamento: O presente estudo não teve fontes de financiamento externas.

 Original Article Achievement of LDL-Cholesterol Goals after Acute Myocardial Infarction: Real-World Data from the City of Curitiba Public Health System 0000-0003-4972-5005 Bernardi André 1 2 Olandoski Marcia 1 Erbano Lucas Olandoski 1 Guarita-Souza Luiz Cesar 1 Baena Cristina Pellegrino 1 0000-0002-1397-0634 Faria-Neto José Rocha 1 Brazil Faculdade de Medicina, Pontifícia Universidade Católica do Paraná, Curitiba, PR – Brazil Brazil Hospital Universitário Evangélico Mackenzie, Curitiba, PR – Brazil Mailing Address: André Bernardi • Rua Eduardo Sprada, 630. Postal Code 81.220-000, Curitiba, PR - Brazil E-mail: bernardiandre@hotmail.com

Author Contributions

Conception and design of the research: Bernardi A, Erbano LO, Guarita-Souza LC, Baena CP, Faria-Neto JR; Acquisition of data: Bernardi A, Olandoski M, Erbano LO; Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content: Bernardi A, Olandoski M, Guarita-Souza LC, Baena CP, Faria-Neto JR; Statistical analysis: Olandoski M, Erbano LO, Faria-Neto JR; Writing of the manuscript: Bernardi A, Faria-Neto JR.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

 Abstract Background

Reduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries.

 Objective

To evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI).

 Methods

This retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05.

 Results

Of 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70–99, 50–69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases.

 Conclusion

In the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.

 Cardiovascular Diseases Myocardial Infarction Dyslipidemias Secondary Prevention Diabetes Mellitus Choleterol LDL Epidemiology Prevention and Control Risk Factors Introduction

Cardiovascular diseases (CVDs) are the leading cause of death in Brazil and worldwide. Globally, it is estimated that there were 18 million deaths from CVDs in 2017, 85% of which were attributed to ischemic heart and cerebrovascular diseases.1 According to the Cardiovascular Statistics – Brazil, approximately 388,268 people died from CVDs in this country.2 Although the mortality rate for ischemic heart disease (IHD) remained stable in the 2000s,3 current data have shown that age-standardized mortality rate from IHD has been decreasing in Brazil.2

High plasma low-density lipoprotein cholesterol (LDL-c) levels are closely correlated with increased cardiovascular risk, regardless of the age group.4 Moreover, reduction in LDL-c is associated with reduced cardiovascular risk: a 39 mg/dL decrease is associated with an approximate 20% reduction in the risk of major cardiovascular events,5 an effect that is similar between sexes.6 In patients at high risk for cardiovascular events, especially those with established coronary disease, massive LDL-c reductions with higher doses of statins have shown better results than those for lower doses.7,8 Similarly, additional reductions in LDL-c using additional therapies combined with statins in highest-risk patients at the optimized maximum doses are also associated with further reduction in new events.9,10

Although an optimal minimum LDL-c level at which there is no risk for CVDs has not been identified, the current consensuses and guidelines seek to establish lipid goals to guide individualized medical care.11-13 These goals may be expressed as absolute LDL-c target values or as minimum percentages of LDL-c reduction. However, many high-risk patients are not achieving the recommended lipid goals,14 even under lipid-lowering therapy.15 This is a multifactorial problem requiring quantification in specific local contexts to ensure the local feasibility and effectiveness of the proposed solutions.16 In Brazil, although health is considered a duty of the State, access to potent statins is limited in the Unified Health System (SUS), the Brazilian public health system that assists more than 70% of the population.17

Until now, a few real-world studies have been conducted in Brazil, showing that patients at cardiovascular risk are achieving the recommended lipid goals.18,19 The objective of this study was to determine the percentage of patients in the public health system from the city of Curitiba, Brazil, who achieved the LDL-c goals after admission for acute myocardial infarction (AMI), including both the attainment of the target LDL-c level and the percentage of LDL-c reduction compared to the levels before AMI.

 Method

This retrospective cohort study was conducted using the Municipal Health Secretariat of Curitiba (SMS) database containing all information on patients admitted to the city’s public health system from the date of admission to the date of discharge. This study was approved by the SMS Research Ethics Committee (REC) and by the academic institution involved.

The patient cohort selected from the database included those of both sexes aged 18 and over, who were admitted to a local public hospital with primary diagnosis of AMI (code ICD-I21) between January 2008 and December 2015. The laboratory test results were obtained from a second database and patient IDs were thoroughly checked to avoid duplication and inconsistency. Duplicate cases and cases with inconsistencies were excluded. Patients without at least one LDL-c value recorded in the year following AMI were also excluded. A search was performed in the laboratory database to find those patients (among the included patients, i.e., those with at least one test after the AMI) who also had at least one LDL-c test in the year before the AMI to calculate the percentage reduction.

LDL-c evaluation

The last LDL-c value, based on the Friedewald formula, recorded in the database following AMI, i.e., the most distant from the date of the AMI, was obtained, except for patients with triglycerides over 400 mg/dL. The percentages of patients who achieved mean LDL-c levels <50, 50–69, 70–99, or ≥100 mg/dL were determined.

To determine the percentage reduction achieved, the database was searched for patients with at least one LDL-c test in the year before the AMI. In cases of patients with more than one test, the LDL-c value closest to the acute event was used. The LDL-c value closest to the AMI in the year before the event was compared to the last value obtained after the AMI. The percentages of patients who achieved LDL-c reductions of 50–100% or <50% or with <50% or 50–100% increases were also determined.

 Statistical Analysis

A descriptive statistical analysis of the data was carried out. The results were expressed as means and standard deviations (quantitative variables) or as frequencies and percentages (categorical variables). Paired Student’s t-test was used to compare LDL-c before and after AMI. Data normality was analyzed by Kolmogorov-Smirnov test. Statistical significance was accepted for p <0.05. Data were analyzed using IBM SPSS Statistics v.20.0. Armonk, NY: IBM Corp.

 Results

Of 7,066 total patients admitted for AMI between January 2008 and December 2015, 61 were excluded due to at least one of the exclusion criteria (duplication or inconsistency in dates of admission). Of the 7,005 remaining cases, 5,554 were excluded for lack of LDL-c results after the AMI. Therefore, the level of LDL-c after the AMI event was evaluated in 1,451 cases (Figure 1). Of these, 377 patients also had at least one test in the year before the AMI, which allowed calculation of the percentage variation.

– Flowchart of study sample characteristics. AMI: Acute myocardial infarction; LDL-c: Low-density lipoprotein cholesterol.

The mean age of the 1,451 patients was 60.8±11.4. Table 1 shows the mean and the standard deviation (SD) of LDL-c among the 1,451 cases after the AMI event. The mean time to the last LDL-c test performed after the AMI was 32.7 months. Figure 2 shows the patients’ percentages of LDL-c levels. Thus, only 28.9% of the patients had LDL-c levels <70 mg/dL after AMI.

– Mean and standard deviation of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol and triglycerides among the 1,451 cases after acute myocardial infarction
Mean SD
LDL-c (mg/dL) 93.3 34.2
HDL-c (mg/dL) 42.9 11.6
Total cholesterol (mg/dL) 168.1 39.8

LDL-c: Low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol; SD: standard deviation.

– Distribution of low-density lipoprotein cholesterol (LDL-c) levels (n=1,451). LDL-c: Low-density lipoprotein cholesterol.

LDL-c values after AMI, among the 377 patients with LDL-c data in the year before the AMI and at least one LDL-c test after the event, were as follows: in the same range as before (40.3%), in a lower range than before (53.3%), and in a higher range than before (6.4%) (Table 2). The mean time between the LDL-c tests before and closest to the AMI and the event itself was 4.8 months. The mean LDL-c concentrations (Figure 3) were 128.0 and 92.2 mg/dL before and after AMI, respectively (Table 3). Figure 4 shows that 19.3% of patients had a more than 50% reduction in LDL-c levels after AMI. Additionally, approximately 82% of the patients achieved some degree of LDL-c reduction (Figure 4).

– Distribution of low-density lipoprotein cholesterol levels before and after acute myocardial infarction
LDL-c after AMI (mg/dL) LDL-c before AMI (mg/dL) Total
<50 50–69 70–99 ≥100
<50 1 6 8 11 26
0.3% 1.6% 2.1% 2.9%
50–69 2 6 29 56 93
0.5% 1.6% 7.7% 14.6%
70–99 2 4 31 93 130
0.5% 1.3% 8.2% 24.4%
≥100 0 0 13 115 128
0.0% 0.0% 3.7% 30.2%
Total 6 17 82 272 377

LDL-c: Low-density lipoprotein cholesterol; AMI: acute myocardial infarction.

– Box-plot for low-density lipoprotein before and after acute myocardial infarction. Student’s t-test, p<0.05. AMI: acute myocardial infarction; LDL-c: Low-density lipoprotein cholesterol.

– Mean and decrease in low-density lipoprotein cholesterol before and after acute myocardial infarction among the 377 cases
Variable Mean SD p*
Before AMI (mg/dL) 128.0 42.7 <0.001
After AMI (mg/dL) 92.2 36.9
Decrease (absolute) (mg/dL) 35.7 40.1
Decrease (relative) (%) 24.3% 28.4%

*Paired Student’s t test, p<0.05. AMI: acute myocardial infarction; SD: standard deviation.

– Distribution of patients according to the change in low-density lipoprotein cholesterol before and after acute myocardial infarction. LDL-c: Low-density lipoprotein cholesterol.

Discussion

Despite the effectiveness of lipid reduction on the reduction of cardiovascular events, many high-risk patients are not achieving the recommended lipid goal. This novel study conducted with data on AMI patients admitted to the public health system of Curitiba found that approximately 82% of the patients achieved some degree of LDL-c reduction, with only approximately 30% attaining mean levels <70 mg/dL and approximately 20% having a reduction >50% compared to the levels before AMI.

The results of this study are similar to those conducted in very different socioeconomic contexts. Recent data from 27 European countries showed that, among 8,261 coronary patients included in the EUROASPIRE V study, 80% were using statins and 71% had LDL-c concentrations ≥70 mg/dL.15 In an older US study also evaluating patients after acute coronary syndrome (ACS) through assessment of lipid control in the first year after the event, only 31% of patients achieved the target LDL-c level <70 mg/dL.20 The data obtained in this study are alarming because these are post-ACS patients, a population at very high risk for new cardiovascular events in the short- to medium-term. The GRACE Registry showed that approximately 10% of patients discharged after an ACS will suffer a non-fatal AMI or a cardiovascular-related death within six months.21 A more recent subanalysis of patients with prior AMI included in the FOURIER study demonstrated that a more recent AMI presents a higher risk for a new cardiovascular event than a more distant AMI (more than two years) and these patients are precisely the ones who benefit from a more aggressive lipid reduction.22

The proposed goals for LDL-c levels were extrapolated from the results of studies with fixed doses of statins because the first study aiming at a specific LDL-c target of 25–50 mg/dL was only recently conducted.23 Therefore, in 2013, the American Heart Association and the American College of Cardiology stopped recommending a specific LDL-c goal and proposed the treatment of high-risk patients with high doses of potent statins capable of reducing LDL-c by >50% based on the results of randomized intervention studies conducted in these populations.24 A clinical study comparing strategies to reduce cardiovascular risk (level attained or percentage of reduction) to determine which is the most effective has not yet been performed, but an analysis of data on 13,937 patients from the three distinct studies on secondary prevention with statins suggests that a >50% reduction would reduce the risk incrementally, even in patients with LDL-c levels <70 mg/dL.25

In the present sample, more patients achieved LDL-c levels <70 mg/dL than those achieving a >50% reduction. This may be explained by the fact that the percentage of reduction is directly associated with the use of high-dose potent statins. Access to these medications within the Brazilian public health system is restricted and the unavailability of these medications in this system is a recognized barrier to their use.26 Lower use of medications necessary for secondary prevention in lower-income countries has been reported. For instance, the PURE study reported 66.5% and 3.3% statin use for secondary prevention in high-and low-income countries, respectively.27

By the time this study was conducted, the 5th Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis28 recommended LDL-c goals under 70 mg/dL for patients with high cardiovascular risk. Moreover, the recommendation to lower LDL-c by at least 50% appears only in the 2017 Brazilian guideline.11Current evidence indicates that the clinical benefit does not depend on the type of statin used but rather on the extent of LDL-c reduction. Most importantly, it is necessary to assess the patient’s cardiovascular risk and initiate treatment aiming at adequate risk reduction. For very high-risk individuals, an LDL-c goal of <55 mg/dL and a reduction of ≥50% from baseline LDL-c should be achieved.13

The American Association of Clinical Endocrinologists and the American College of Endocrinology proposed an LDL-c goal of <55 mg/dL for a new category of risk termed “extreme risk”.29 This category refers to patients with progressive atherosclerotic cardiovascular disease (ASCVD), including unstable angina persisting after an LDL-c of <70 mg/dL has been achieved, or clinically stable ASCVD with diabetes, stage 3 or 4 chronic kidney disease and/or heterozygous familial hypercholesterolemia, or patients with a history of premature ASCVD (<55 years of age for men or <65 years of age for women). In this study, only 7.4% of patients achieved levels lower than 50 mg/dL after AMI.

Whereas the American guidelines recommend lowering LDL-C levels by at least 50% of the baseline in coronary patients,30 the European guidelines propose a target LDL-c of <55 mg/dL and at least a 50% reduction in LDL-c in patients with documented coronary artery disease (CAD).13 The American and European guidelines recommend treatment with a combination of lipid-lowering drugs to achieve these goals. However, the American guideline agrees that the focus is LDL-c reduction, mainly based on a >50% reduction from the baseline value rather than on the attainment of specific LDL-c target levels. However, it is important to highlight that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe are reasonable in patients with AMI considered to be at very high risk and with LDL-c ≥ 70 mg/dL on maximally tolerated statins.

The results of the IMPROVE-IT study showed that significantly more patients with CAD treated with a combination of statin and ezetimibe achieved the LDL-c goals compared to statins alone.31

Study limitations

This analysis has several potential limitations. Only a minority of patients admitted for AMI in the public health system of Curitiba underwent a cholesterol test in the year after the AMI. Many patients that were treated for the event in Curitiba were likely not actually from the city. Therefore, the loss to outpatient follow-up was significant because these patients returned to their hometowns for medical follow-up and secondary prevention care or even discontinued follow-up care. No LDL-c data from patients who did not receive outpatient follow-up in the public health system of Curitiba were obtained. Nevertheless, the analysis cohort was representative of a real-world population of Curitiba with myocardial infarction that survived hospitalization. Lastly, the greatest limitation of this study was the absence of sociodemographic and medication details, either regarding the use (or not) of statins or the doses administered before and after AMI.

 Conclusion

After AMI, a minority of cardiovascular high-risk patients achieved the recommended LDL-c goals in this cohort of patients admitted to the city of Curitiba public health system. The similarity between the results of this study and those from studies conducted in countries with very different socioeconomic conditions suggests that other factors, probably related to physicians and patients themselves, may be associated with this scenario.

Sources of Funding: There were no external funding sources for this study.