Proprotein Convertase 9

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Editorial

Discordance of Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol with Severity of Coronary Artery Disease

Cardiovascular diseases (CVDs) are the leading cause of mortality world. Dyslipidemia is a risk and causal factor and is the focus of the therapy for primary and secondary prevention of CVDs.

There is consensus and broad understanding of the causal mechanisms of low-density lipoproteins (LDL) in CVDs, and the benefit of the hypolipidemic therapy, with a magnitude of effect proportional to the reduction in serum levels. However, despite intensive use of lipid lowering agents, there remains a residual risk, a constant target of research and therapy.

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Review Article

PCSK9 Inhibitors: Clinical Relevance, Molecular Mechanisms, and Safety in Clinical Practice

Filipe Ferrari et al. Ricardo Stein Marcelo Trotte Motta Emilio Hideyuki Moriguchi

Abstract

Coronary artery disease (CAD) is one of the leading causes of mortality. High circulating levels of low-density lipoprotein (LDL) in the blood are associated with cardiovascular mortality, whether through an etiological role or through its association with the progression of CAD per se. Randomized clinical trials have shown that, when LDL levels are reduced, cardiovascular risk is also reduced, which reinforces this association. The first major trial involving a hypolipidemic agent of the statin family, the Scandinavian Simvastatin Survival Study (4S), was published in 1994 and found a significant reduction in mortality in patients at high cardiovascular risk. However, even in subsequent studies with different statins, a residual risk persisted, and this seems not to have changed over time; it is speculated that this risk may be due to statin intolerance. In this scenario, the potential exists for novel hypolipidemic agents to drive a true revolution in the therapy of dyslipidemia. The recent discovery of PCSK9 inhibitors (PCSK9i), a class of hypolipidemic monoclonal antibodies, is extremely promising. PCSK9 inhibition is capable of promoting a mean LDL reduction of up to 60%, with potential for very significant clinical repercussions, as every 38 mg/dL reduction in LDL appears to be associated with a 22% reduction in cardiovascular risk. This review addresses a brief history of PCSK9i, major trials of these drugs, cardiovascular outcomes, and aspects related to their efficacy and safety. Finally, the molecular mechanisms and possible pleiotropic effects of PCSK9i are also discussed.

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Viewpoint

Indications of PCSK9 Inhibitors for Patients at High and Very High Cardiovascular Risk

Paulo Eduardo Ballvé Behr et al. Emilio Hideyuki Moriguchi Iran Castro Luiz Carlos Bodanese … Oscar Pereira Dutra Paulo Ernesto Leães Pedro Pimentel Filho

LDL-C as a risk factor

The causality of plasma LDL-C levels and reduced LDL-C uptake mediated by the LDL-C receptor in the pathophysiology of CVD has been very consistently established. For patients at very high risk for premature events, such as those with familial hypercholesterolemia (FH), an elevated LDL-C level is an extremely prevalent risk factor.

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Discordance of Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol with Severity of Coronary Artery Disease

PCSK9 Inhibitors: Clinical Relevance, Molecular Mechanisms, and Safety in Clinical Practice

Abstract

Indications of PCSK9 Inhibitors for Patients at High and Very High Cardiovascular Risk

LDL-C as a risk factor

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Electronic Document Format (Vancouver)

Electronic Document Format (ABNT)

Electronic Document Format (APA)

Electronic Document Format (ISO)

Electronic Document Format (Vancouver)

Electronic Document Format (ABNT)

Electronic Document Format (APA)

Electronic Document Format (ISO)