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1.
Expert Opin Pharmacother ; 21(3): 353-363, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31893957

RESUMO

Introduction: Scientific evidence on subjects treated with statin or other lipid-lowering treatments has established that treatments aiming to lower low-density lipoprotein cholesterol (LDL-C) can reduce atherosclerosis. PCSK9 inhibitors (PCSK9-i), thanks to their efficacy in reducing LDL-C constitute a further step in the treatment of dyslipidemia and cardiovascular (CV) diseases.Areas covered: The purpose of this narrative review is to summarize the current knowledge of PCSK9-i, with particular regard to pharmacodynamic, pharmacokinetic, and clinical data on evolocumab and alirocumab.Expert opinion: PCSK9-I are effective in reducing atherosclerotic events through their significant LDL-C-lowering action similarly to statins. Furthermore, these drugs can be considered safe and well-tolerated. However, some controversies remain with regard to their efficacy in reducing mortality and the paucity of data on both pleiotropic effects and long-term safety of these drugs. However, future studies will focus on understanding the effects of very low cholesterol levels on health. At present, we know that the genetic model of PCSK9 deficiency is characterized by very low LDL-C levels without particular health problems. Yet, we do not know the effect of prolonged PCSK9 inhibition induced by antibody action during the lifetime of normal subjects.


Assuntos
Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue
3.
Prog Cardiovasc Dis ; 62(5): 395-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31715195

RESUMO

Statin therapy is effective in primary and secondary prevention, but substantial residual risk remains on statin treatment, especially among high risk and very high risk patients. Add-on therapy with ezetimibe and proprotein convertase subtilisin /kexin type 9 (PCSK9) inhibitors provides additional risk reduction through further reduction in low density lipoprotein cholesterol. Elevated triglycerides/triglyceride rich lipoproteins contribute to atherogenesis and to the residual risk on statin therapy. Addition of icosapent ethyl to statins has recently been shown to markedly lower risk of ASCVD events in patients with established atherosclerotic CVD (ASCVD) and high risk patients with type II diabetes mellitus. These data are discussed in the context of current guidelines and synthesized in a decision pathway to guide combination lipid-lowering therapy in patients at high ASCVD risk.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Serino Proteinase/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento , Triglicerídeos/sangue
4.
Prog Cardiovasc Dis ; 62(5): 414-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31669498

RESUMO

Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease. FH is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (APOB) and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9). However, the phenotype may be encountered in individuals not carrying the latter monogenic defects, in approximately 20% of these effects of polygenes predominate, and in many individuals no molecular defects are encountered at all. These so-called FH phenocopy individuals have an elevated atherosclerotic cardiovascular disease risk in comparison with normolipidemic individuals but this risk is lower than in those with monogenic disease. Individuals with FH are exposed to elevated LDL-C levels since birth and this explains the high cardiovascular, mainly coronary heart disease, burden of these subjects. However, recent studies show that this risk is heterogenous and depends not only on high LDL-C levels but also on presence of previous cardiovascular disease, a monogenic cause, male sex, smoking, hypertension, diabetes, low HDL-cholesterol, obesity and elevated lipoprotein(a). This heterogeneity in risk can be captured by risk equations like one from the SAFEHEART cohort and by detection of subclinical coronary atherosclerosis. High dose high potency statins are the main stain for LDL-C lowering in FH, however, in most situations these medications are not powered enough to reduce cholesterol to adequate levels. Ezetimibe and PCSK9 inhibitors should also be used in order to better treat LDL-C in FH patients.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Aterosclerose/epidemiologia , Aterosclerose/genética , Biomarcadores/sangue , Ezetimiba/uso terapêutico , Predisposição Genética para Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Fenótipo , Pró-Proteína Convertase 9/antagonistas & inibidores , Pró-Proteína Convertase 9/metabolismo , Medição de Risco , Fatores de Risco , Inibidores de Serino Proteinase/uso terapêutico , Resultado do Tratamento
5.
Expert Opin Drug Saf ; 18(12): 1191-1201, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31623472

RESUMO

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that have been developed since the discovery of the PCSK9 protein in 2003. In addition to background statin treatment, they reduce low-density lipoprotein cholesterol (LDL-C) to unprecedented levels and have shown encouraging results in improving cardiovascular events. Concerns regarding the safety of PCSK9 inhibitors and very low LDL-C have somewhat been allayed after several longer-term prospective studies.Areas covered: A comprehensive literature search was carried out including article searches in electronic databases (EMBASE, PUBMED, OVID) and reference lists of relevant articles. This review examines novel research concerning PCSK9 monoclonal antibodies and cardiovascular outcomes with a special focus on their safety and tolerability. The safety of very low LDL-C concentrations and the link between LDL-C lowering and diabetes is also discussed.Expert opinion: PCSK9 monoclonal antibodies when added to background statin therapy, lowers LDL-C to previously unattainable levels. This is safe with little undesirable effects and impacts positively on cardiovascular disease. Current guidance limits their use to primary prevention. Cost effectiveness should be taken into consideration before allowing a wider use of this new class of cholesterol lowering therapy and more data on their long-term safety is welcome.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticolesterolemiantes/administração & dosagem , Pró-Proteína Convertase 9/antagonistas & inibidores , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Prevenção Primária , Pró-Proteína Convertase 9/imunologia
6.
Clín. investig. arterioscler. (Ed. impr.) ; 31(5): 241-243, sept.-oct. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-184168

RESUMO

Se trata de un paciente con hipercolesterolemia familiar heterocigota y antecedentes de infarto agudo de miocardio, que es remitido a la unidad de lípidos de nuestro centro para ajuste del tratamiento hipocolesterolemiante. Dado que no alcanza los objetivos terapéuticos con tratamiento oral, comienza tratamiento con sesiones quincenales de aféresis de colesterol LDL, que mantiene durante 8 años. Con la introducción y disponibilidad de los inhibidores de la PCSK9, se presenta una nueva opción de tratamiento para este paciente


It is a patient with heterozygous familial hypercholesterolemia and a personal history of acute myocardial infarction, which is referred to our lipid unit for hypocholesterolemic treatment adjustment. Since he does not reach therapeutic goals with oral medication, he starts a treatment with fortnightly sessions of LDL-apheresis, which he keeps for 8 years. With the introduction and availability of PCSK9 inhibitors, a new treatment option is possible for this patient


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/antagonistas & inibidores , Hiperlipoproteinemia Tipo II/diagnóstico , Infarto do Miocárdio/complicações , Anticorpos Monoclonais/farmacologia , LDL-Colesterol/antagonistas & inibidores , Anticolesterolemiantes , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Pró-Proteína Convertase 9/administração & dosagem , Pró-Proteína Convertase 9/metabolismo , Lipoproteínas LDL/efeitos dos fármacos
7.
Int J Clin Pharmacol Ther ; 57(12): 575-589, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549625

RESUMO

OBJECTIVE: Bococizumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, has been shown to reduce low-density lipoprotein cholesterol (LDL-C). Here, we describe the pharmacokinetics and pharmacodynamics of bococizumab and its effect on lipoprotein particle composition and other biomarkers, based on a double-blind, placebo-controlled, randomized, dose-ranging study. MATERIALS AND METHODS: The study consisted of two populations: Japanese subjects with uncontrolled LDL-C (LDL-C ≥ 100 mg/dL) despite treatment with atorvastatin (n = 121) and Japanese subjects naïve to lipid-lowering agents with LDL-C ≥ 130 mg/dL (n = 97). Subjects were randomized to receive either bococizumab 50, 100, or 150 mg or placebo, every 2 weeks. One arm of subjects in the ator-vastatin-treated population received ezetimibe 10 mg instead of bococizumab. RESULTS: In both populations, bococizumab exposure increased with increasing dose, and subjects with lower body weights tended to have higher exposures. Bococizumab treatment was associated with a dose-dependent reduction in LDL particles and a small increase in total high-density lipoprotein (HDL) particles. Significant reductions in lipoprotein-associated phospholipase A2 (Lp-PLA2) were observed for bococizumab-treated subjects but not for subjects treated with placebo or ezetimibe. CONCLUSION: Increased bococizumab dosage resulted in increased exposure. Levels of LDL and HDL particles and biomarkers such as Lp-PLA2 were also altered with bococizumab treatment. (ClinicalTrials.gov identifier: NCT02055976).
.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticolesterolemiantes/farmacocinética , Hipercolesterolemia/terapia , Pró-Proteína Convertase 9/antagonistas & inibidores , Atorvastatina/uso terapêutico , Biomarcadores/sangue , Método Duplo-Cego , Humanos , Japão , Resultado do Tratamento
9.
Clin Adv Periodontics ; 9(1): 20-23, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31490035

RESUMO

INTRODUCTION: Monoclonal antibodies against proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a newly-introduced therapeutic approach against hypercholesterolemia. Clinical trials have reported few adverse effects of PCSK9 inhibitors and there are no reports of oral adverse effects. We present the case of a patient that showed gingival discomfort on eating and toothbrushing, coupled with the presence of gingival ischemia and petechiae, 3 days after a subcutaneous abdominal injection of 75-mg alirocumab for hypercholesterolemia, and contemplate on their possible pathogenesis. CASE PRESENTATION: Αn 81-year-old male presented with gingival discomfort during eating and toothbrushing, 3 days after receiving a subcutaneous abdominal injection of alirocumab. Intraoral examination revealed that the anterior free and attached gingiva of both jaws appeared pale and the surrounding mucosa showed confluent petechiae that were more evident on the anterior palatal gingiva. The patient was asked to brush his teeth with a soft toothbrush and use a mouthwash containing hydrogen peroxide three times daily. At the 8-day re-examination he was symptom-free, and the mucosa appeared totally normal. At the 5-month follow-up visit he reported having the same symptoms after each one of the 12 doses of alirocumab he received. CONCLUSIONS: Adverse dugs effects associated with subcutaneous injection of alirocumab may manifest in the gingiva. Therefore, oral and periodontal examination should be included in the regular follow-up of patients medicated with this drug.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Hipercolesterolemia , Isquemia , Idoso de 80 Anos ou mais , Gengiva/diagnóstico por imagem , Humanos , Hipercolesterolemia/tratamento farmacológico , Isquemia/induzido quimicamente , Masculino , Pró-Proteína Convertase 9/antagonistas & inibidores , Púrpura
10.
Ned Tijdschr Geneeskd ; 1632019 08 29.
Artigo em Holandês | MEDLINE | ID: mdl-31483586

RESUMO

The new Dutch guideline on cardiovascular risk management has lowered the target value for LDL cholesterol from 2.5 to 1.8 mmol/L. The authors claim transparency, yet there is no hard scientific evidence that supports this new target value. There is only a theoretical model developed by theCholesterol Treatment Trialists' (CTT) Collaboration Group. This group has the raw data of the cholesterol trials and they have signed confidentiality agreements with manufacturers stating that they will not share this data with others. This group also produced the Cochrane review on primary cardiovascular prevention with statins. If the real effect of cholesterol-lowering drugs is not disclosed to the population in a transparent manner, this will be done through independent channels with the message 'leave those PCSK9 inhibitors alone until there is hard scientific evidence for their efficacy.' And if patients suffer greatly from, for example,muscle pain, diabetes or amnesia due to taking statins, in accordance with the guideline they will decide for themselves whether or not to continue taking it.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Revelação , Medicina Baseada em Evidências , Disseminação de Informação , Guias de Prática Clínica como Assunto , Anticolesterolemiantes/uso terapêutico , Pesquisa Biomédica , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , LDL-Colesterol/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Países Baixos , Prevenção Primária , Pró-Proteína Convertase 9/antagonistas & inibidores , Valores de Referência , Fatores de Risco , Gestão de Riscos , Resultado do Tratamento
12.
Curr Top Med Chem ; 19(20): 1790-1817, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31400268

RESUMO

BACKGROUND: Cardiovascular diseases remain the leading cause of morbidity and mortality in the world, with elevated Low-Density Lipoprotein-Cholesterol (LDL-C) levels as the major risk factor. Lower levels of LDL-C can effectively reduce the risk of cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in regulating the degradation of hepatic LDL receptors that remove LDL-C from the circulation. PCSK9 inhibitors are a new class of agents that are becoming increasingly important in the treatment to reduce LDL-C levels. Two PCSK9 inhibitors, alirocumab and evolocumab, have been approved to treat hypercholesterolemia and are available in the United States and the European Union. Through the inhibition of PCSK9 and increased recycling of LDL receptors, serum LDL-C levels can be significantly reduced. OBJECTIVE: This review will describe the chemistry, pharmacokinetics, and pharmacodynamics of PCSK9 inhibitors and their clinical effects.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/farmacologia , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Pró-Proteína Convertase 9/metabolismo
13.
Rev Port Cardiol ; 38(6): 391-405, 2019 06.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31324407

RESUMO

Reducing low-density lipoprotein cholesterol (LDL-C) levels is one of the most important strategies for reducing the risk of cardiovascular events. However, in clinical practice, a high proportion of patients do not achieve recommended LDL-C levels through lifestyle and lipid-lowering therapy with statins and ezetimibe. PCSK9 inhibitors (PCSK9i) are a new therapeutic option that significantly (50-60%) reduces LDL-C levels, which in clinical trials translates into an additional reduction in risk for cardiovascular events, and has a good safety profile. However, it is a high-cost therapy, and therefore its use in clinical practice should take its cost-effectiveness into account. Priority should be given to use in patients at higher cardiovascular risk and those in whom high LDL-C levels persist despite optimal lipid-lowering therapy. This consensus document aims to summarize the main data on the clinical use of PCSK9i and to make recommendations for Portugal on the profile of patients who may benefit most from this therapy.


Assuntos
LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/efeitos dos fármacos , Dislipidemias/sangue , Dislipidemias/epidemiologia , Humanos , Incidência , Portugal/epidemiologia
14.
J Assoc Physicians India ; 67(4): 74-85, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31311223

RESUMO

The burden of atherosclerotic cardiovascular (CV) disease is alarmingly high and increasing in our country. Dyslipidemia is one of the major modifiable risk factors, and INTERHEART study showed that dyslipidemia had the highest population attributable risk for myocardial infarction. In the management of dyslipidemia, low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target. In addition to therapeutic lifestyle changes, statins and ezetimibe effectively lower LDL-C and consequently improve CV outcomes. However, there are situations where these drugs fall short of achieving the target or they may not be well tolerated.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Anticolesterolemiantes , LDL-Colesterol , Índia , Pró-Proteína Convertase 9/metabolismo
15.
Expert Opin Pharmacother ; 20(16): 2007-2017, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31344332

RESUMO

Introduction: Cardiovascular disease (CVD) frequently co-exists with chronic kidney disease (CKD). Patients with concomitant CVD and CKD are at very high risk of CVD events. Areas covered: This narrative review discusses the use of hypolipidaemic drugs in patients with both CVD and CKD. Current guidelines are considered together with the evidence from randomised controlled clinical trials. Expert opinion: Statins are the first-line lipid-lowering therapy in patients with CVD and CKD. Some statins require dose adjustments based on renal function, whereas atorvastatin does not. Ezetimibe can be prescribed in patients with CVD and CKD, usually combined with a statin. According to current guidelines, statin±ezetimibe therapy should not be initiated, but should be continued, in dialysis-treated CKD patients. Fenofibrate (dose adjusted or contra-indicated according to renal function) and omega 3 fatty acids lower triglyceride levels; whether they also exert cardiorenal benefits in patients with CVD and CKD remains to be established. The use of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, cholesterol-reducing nutraceuticals, bempedoic acid and apabetalone in such patients should be investigated. Patients with concomitant CVD and CKD should be treated, in terms of lipid-lowering therapy, early and intensively to minimize their very high risk and possibly, progression of CKD.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , LDL-Colesterol/sangue , Ezetimiba/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Fenofibrato/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia
16.
High Blood Press Cardiovasc Prev ; 26(3): 199-207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236902

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-related discoveries of the turn of the century have translated into substantial novelty in dyslipidemia treatment in the last 5 years. With chronic preventable atherosclerotic cardiovascular diseases (ASCVD) representing an epidemic of morbidity and mortality worldwide, low-density lipoprotein cholesterol (LDL-c) reduction represents a public health priority. By overcoming two major statin-related issues, namely intolerance and ineffectiveness, PCSK9 inhibitors have offered a safe and effective option in selected clinical settings where LDL-c reduction is required. Herein, we recapitulate recent findings, clinical applications, and ASCVD prevention potential of PCSK9 inhibition, with focus on anti-PCSK9 monoclonal antibodies, evolocumab and alirocumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Aterosclerose/enzimologia , Aterosclerose/epidemiologia , Biomarcadores/sangue , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/epidemiologia , Humanos , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
17.
Rev Cardiovasc Med ; 20(1): 1-8, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31184090

RESUMO

Cardiovascular disease is the leading cause of morbidity and mortality globally, as estimated by the World Health Organization, where in 2016, 15.2 million deaths were attributed to ischemic heart disease and stroke. It is therefore essential to try to reduce the incidence of Cardiovascular disease by controlling modifiable risk factors. One such major modifiable risk factor is cholesterol, which influences the pathogenesis and progression of atherosclerosis. Statins are often prescribed to lower blood levels of low density lipoprotein cholesterol, thereby reducing the risk of Cardiovascular disease by approximately 25-35%. However, there is an increasing number of patients (in particular those with intolerance to statin therapy and those with familial hypercholesterolemia) for whom statin therapy alone is not enough to control low density lipoprotein cholesterol. In this review, the regulation of cholesterol metabolism will be discussed with an emphasis on novel cholesterol lowering drugs used in clinical trials. These second-generation drugs, monoclonal antibodies against the low density lipoprotein receptor gene known as proprotein convertase subtilisin/kexin type 9 inhibitors, are expected to be prescribed to patients who are intolerant to statins, as well as in conjunction with statins. Future perspectives of the clinical use of these drugs is also discussed.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Dislipidemias/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/epidemiologia , Humanos , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
18.
Medicina (B Aires) ; 79(2): 104-110, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31048275

RESUMO

LDL-cholesterol (LDL-C) lowering is a primary objective in cardiovascular prevention. Recent studies demonstrated clinical benefit when proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i) were added to the treatment in patients who had not achieved the LDL-C goal despite being treated with high intensity statins and ezetimibe, however the use of these drugs is limited by their cost. The American College of Cardiology, the Argentine Society of Cardiology and the European Society of Cardiology recommend an LDL-C goal less than 70 mg/dl in secondary prevention, determining thresholds of LDL-C to start treatment with PCSK9i of 70, 100 or 140 mg/dl respectively. In order to evaluate the lipid-lowering regimen prescribed in patients hospitalized for acute coronary syndrome or coronary revascularization and analyze the proportion of eligible to be treated with PCSK9i in a real and simulated scenario, we conducted a study that included 351 patients with coronary disease collected from an electronic database of a university hospital. The 48.4% received high intensity statins, 11.4% ezetimibe and 54.7% did not achieve the LDL-C goal of less than 70 mg/dL. Using a simulation model in which all would be treated with high intensity statins and ezetimibe, the eligibility to prescribe PCSK9i was 31.1%, 12.8% and 9.1% according to the C- LDL thresholds determined by the three scientific societies. Our study demonstrated a gap between the consensus recommendations for LDL-C lowering and the current practice that should be minimized to optimize the cost/effectiveness ratio in secondary prevention.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Argentina , Estudos Transversais , Ezetimiba/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Fatores Sexuais , Sociedades Científicas , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
19.
Methodist Debakey Cardiovasc J ; 15(1): 32-38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049147

RESUMO

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins remain the first-line therapy for patients with elevated LDL-C and increased risk. However, many at-risk patients do not achieve adequate LDL-C lowering with statin monotherapy or do not tolerate statins because of side effects. Recent cardiovascular outcome trials involving ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated efficacy of nonstatin therapies in further reducing LDL-C levels and ASCVD risk. This review highlights the available nonstatin therapeutic options and explores important novel therapeutic approaches currently under development.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Ezetimiba/uso terapêutico , Ácidos Graxos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pró-Proteína Convertase 9/antagonistas & inibidores , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
20.
J Atheroscler Thromb ; 26(7): 583-591, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31061262

RESUMO

Lipoprotein(a) [Lp(a)], discovered in 1963, has been associated with atherosclerotic cardiovascular disease (ASCVD) independent of other traditional risk factors, including LDL cholesterol. Lp(a) is an apolipoprotein B (apoB)-containing lipoprotein, which contains an LDL-like particle. Unlike LDL, which is a primary therapeutic target to decrease ASCVD, current guidelines recommend measuring Lp(a) for risk assessments because there is no clear evidence demonstrating the clinical benefit of decreasing Lp(a) using classical drugs such as niacin. However, recent Mendelian randomization studies indicate that Lp(a) causally correlates with ASCVD. In addition, novel drugs, including PCSK9 inhibitors, as well as antisense oligonucleotide for apo(a), have exhibited efficacy in decreasing Lp(a) substantially, invigorating a discussion whether Lp(a) could be a novel therapeutic target for further ASCVD risk reduction. This review aims to provide current understanding, and future perspectives, of Lp(a), which is currently considered a mere biomarker but may emerge as a novel therapeutic target in future clinical settings.


Assuntos
Aterosclerose/sangue , Lipoproteína(a)/sangue , Apolipoproteínas B/sangue , Apolipoproteínas B/química , Aterosclerose/tratamento farmacológico , Biomarcadores/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteína(a)/química , Niacina/uso terapêutico , Oligonucleotídeos Antissenso/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Medição de Risco , Fatores de Risco , Inibidores de Serino Proteinase
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