Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 17.181
Filtrar
1.
Eur J Prev Cardiol ; 28(18): 2001-2009, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33624058

RESUMO

AIM: The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS: Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION: This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Colesterol , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Infarto do Miocárdio/prevenção & controle
2.
Dtsch Med Wochenschr ; 147(15): 1001-1012, 2022 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-35915886

RESUMO

Current dyslipidemia guidelines emphasize statins as the cornerstone of pharmacological lipid-lowering therapy. The cholesterol absorption inhibitor ezetimibe, PCSK9-antibodies, as well as bempedoic acid and inclisiran are newly available options to further reduce LDL-cholesterol. Since modern lipid-lowering therapy is characterized by an individual, "treat-to-target" approach the aim of this review is to provide a better understanding of cholesterol metabolism to guide decision-making and the rational for using early individualized combination therapies.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9
3.
J Am Heart Assoc ; 11(15): e024531, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916348

RESUMO

Background Bempedoic acid (BA) inhibits ATP-citrate lyase in the cholesterol synthesis pathway and lowers low-density lipoprotein cholesterol (LDL-C). As with other lipid-lowering therapies, interindividual variation in response to BA was observed in clinical trials. We characterized LDL-C response to BA using guideline-defined statin intensity categories and identified clinical factors associated with enhanced LDL-C lowering with BA. Methods and Results This post hoc analysis used pooled data from 4 phase 3 studies. Patients were randomized 2:1 to once-daily BA 180 mg (n=2321) or placebo (n=1167) for 12 to 52 weeks and grouped based on percent change in LDL-C from baseline to week 12 according to guideline-established statin intensity categories. Factors associated with ≥30% reduction in LDL-C were identified using logistic regression analyses. From baseline to week 12, BA lowered LDL-C levels comparable to a moderate- or high-intensity statin (≥30%) in 28.9% of patients; this degree of LDL-C lowering was observed in 50.9% of patients not receiving background statin therapy. In a multivariable analysis, the absence of statins, female sex, a history of diabetes, ezetimibe use, and higher high-sensitivity C-reactive protein level were associated with increased rates of achieving ≥30% LDL-C reduction with BA (P<0.01 for each). Conclusions A large percentage of patients receiving BA achieved LDL-C reductions comparable to a moderate- or high-intensity statin. Factors including statin absence, female sex, diabetes history, ezetimibe use, and a higher high-sensitivity C-reactive protein level may be useful to identify patients who may have a greater LDL-C reduction with BA. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02666664, NCT02991118, NCT02988115, NCT03001076.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/uso terapêutico , Proteína C-Reativa , Colesterol , LDL-Colesterol , Ácidos Dicarboxílicos , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Ácidos Graxos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resultado do Tratamento
4.
Drug Des Devel Ther ; 16: 2177-2186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832642

RESUMO

Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient's elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.


Assuntos
Anticolesterolemiantes , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Colesterol , LDL-Colesterol , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Humanos , Rosuvastatina Cálcica/uso terapêutico , Sinvastatina , Resultado do Tratamento
5.
Viruses ; 14(7)2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35891519

RESUMO

Many viruses require the maintenance of lysosomal cholesterol homeostasis for a successful infection; however, the role of lysosomal cholesterol homeostasis in the alphaherpesvirus life cycle is not clear. Here we show that the lysosomal cholesterol transport inhibitor U18666A interferes with the replication of pseudorabies virus (PRV), a member of the alphaherpesvirus subfamily. The treatment with U18666A caused a significant reduction in the production of infectious virus particles. The U18666A treatment was shown to suppress the release of PRV particles. Pretreating PRV virions with U18666A did not affect virus production, whereas pretreating target cells with U18666A led to a substantial reduction in virus yield. Our previous study showed that two cyclodextrin derivatives, 2-hydroxypropyl-ß-cyclodextrin (HPßCD) and 2-hydroxypropyl-γ-cyclodextrin (HPγCD), can rescue the cholesterol accumulation defect in primary fibroblasts derived from a Niemann-Pick disease type C (NPC) patient. Here, we demonstrate that treatment with HPßCD or HPγCD not only rescues the U18666A-induced cholesterol accumulation but also rescues the U18666A-induced inhibition of PRV production. Collectively, our data suggest that U18666A interferes with PRV infection via altering cellular functions that are critical for the viral life cycle and may include lysosomal cholesterol homeostasis.


Assuntos
Anticolesterolemiantes , Herpesvirus Suídeo 1 , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Androstenos/farmacologia , Animais , Anticolesterolemiantes/farmacologia , Colesterol , Humanos
6.
Int Heart J ; 63(4): 669-677, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35831153

RESUMO

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors significantly reduce low-density lipoprotein cholesterol (LDL-C) and improve the prognosis of patients with acute coronary syndrome (ACS). However, the feasibility and safety of early application of PCSK9 inhibitors on the basis of statins combined with ezetimibe to strengthen lipid lowering in extremely high-risk coronary heart disease populations are still unknown.This study was a prospective, randomized controlled study. A total of 136 patients with extremely high-risk ACS with LDL-C ≥ 3.0 mmol/L after percutaneous coronary intervention (PCI) treatment were randomly assigned 1:1 to the control group (atorvastatin 40 mg/day and ezetimibe 10 mg/day) or the evolocumab group (evolocumab 140 mg every 2 weeks combined with atorvastatin 40 mg/day and ezetimibe 10 mg/day). We compared the blood lipid profiles, major adverse cardiovascular events (MACEs), and adverse reactions. MACEs included cardiogenic death, nonfatal myocardial infarction, nonfatal stroke, and readmission due to angina. Adverse reactions included allergies, myalgia, poor blood glucose control, and liver damage.Within 1 month, the average level of LDL-C in the evolocumab group decreased from 3.54 to 0.57 mmol/L and that in the control group decreased from 3.52 to 1.26 mmol/L. The LDL-C compliance (< 1.0 mmol/L) rate was significantly increased in the evolocumab group compared with the control group (82.35% versus 22.06%, P < 0.01). The average level of lipoprotein (a) (Lp (a) ) in the control group increased by 9.94 ± 51.93% from baseline after treatment, but evolocumab reduced the Lp (a) level (-38.84 ± 32.40%). Additionally, evolocumab further reduced the levels of apolipoprotein B/A1 (-70.56 ± 22.38% versus -51.29 ± 18.14%), cholesterol (-54.76 ± 18.10% versus -41.16 ± 18.14%), and apolipoprotein B (-66.47 ± 26.89% versus -46.78 ± 24.12%) compared with those in the control group, all P < 0.01. The blood lipid levels of both control and evolocumab groups stabilized after 1 month. During the 3-month follow-up, the incidence of MACEs after PCI was lower in the evolocumab group than in the control group (8.82% versus 24.59%, P = 0.015), and evolocumab combined with statins and ezetimibe did not increase the occurrence of adverse reactions (13.24% versus 11.48%, P = 0.762).In patients with extremely high-risk ACS with high levels of LDL-C, adding evolocumab to their treatment regimen as early as possible may enhance lipid lowering, increase the patient's LDL-C compliance rate in the short term, and improve cardiovascular prognosis but will not increase adverse reactions.


Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/uso terapêutico , Apolipoproteínas , Atorvastatina/uso terapêutico , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos , Prognóstico , Pró-Proteína Convertase 9 , Estudos Prospectivos , Resultado do Tratamento
7.
Kardiologiia ; 62(6): 57-62, 2022 Jun 30.
Artigo em Russo | MEDLINE | ID: mdl-35834343

RESUMO

Inclisiran is a novel hypolipidemic drug that inhibits synthesis of the PCSK9 protein through the process called RNA interference. Inclisiran is a double-stranded, modified RNA bound to the N-acetylgalactosamine (GalNAc) carbohydrate molecule, a ligand of the acialoglycoprotein receptor, that is expressed by hepatocytes. After entering hepatocytes, inclisiran cleaves matrix RNA and, thereby, reduces the PCSK9 protein synthesis. This, in turn, enhances the uptake of circulating low-density lipoproteins (LDL) by specific receptors on hepatocytes, thereby lowering LDL levels in circulation. Efficacy and safety of inclisiran for lowering LDL cholesterol (C) in blood and its effect on the risk of clinical complications of atherosclerosis have been studied in the ORION program that includes multiple clinical trials. According to results of this program, inclisiran effectively reduces both LDL-C levels and the incidence of cardiovascular complications in the absence of clinically significant adverse reactions. An important advantage of inclisiran compared with other lipid-lowering drugs is the administration schedule (twice a year), which allows a considerable improvement of patients' compliance with the treatment and also of the effectiveness of the hypolipidemic treatment.


Assuntos
Anticolesterolemiantes , Pró-Proteína Convertase 9 , Anticolesterolemiantes/efeitos adversos , LDL-Colesterol , Humanos , Hipolipemiantes/efeitos adversos , RNA Interferente Pequeno/efeitos adversos
8.
Lipids Health Dis ; 21(1): 63, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897032

RESUMO

BACKGROUND: To assess the long-term biological coefficient of variation within individuals (CVI) and between individuals (CVG), effect of aging and cholesterol lowering drugs on blood levels of lipids in HIV-1-infected and -uninfected men. METHODS: Bloods were analyzed every six months over 17 years for total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in 140 HIV-uninfected (38-66 years old) and 90 HIV-treated infected (48-64 years old) white Caucasian men to examine CVI, CVG, and the effect of cholesterol lowering drugs (CLDs) on lipid levels, and estimated changes per year of biomarkers. RESULTS: With exception of HDL-C, the long term CVI compared with CVG were higher for serum levels of TC, TGs, and LDL-C in both HIV-1 infected and uninfected men not taking CLDs. Excluding results of TGs in HIV positive men, the CVI compared with CVG were lower for serum levels of TC, HDL-C, and LDL-C in both groups not taking CLDs. There were significant (p < 0.05) differences in the median serum values of lipid biomarkers among 77 HIV negative men taking and 63 not taking CLDs. Also, with exception of HDL, there were significant (p < 0.05) differences in the median values of TC, TGs and LDL-C among 28 HIV positive men taking or not taking CLDs. CONCLUSION: Long term CVI and CVG of biomarkers will be useful for monitoring antiviral therapy side effects on lipid profiles in HIV-infected men. CVI of HIV-infected men for TC, TGs, HDL, LDL were higher significantly than CVI of HIV-uninfected men. Interestingly the long term CVI were higher than CVG for the men, who were on CLDs compared to men not on CLDs. The long-term pattern of CVI and CVG of lipid markers in both HIV-infected and uninfected men on CLDs differed from their short-term pattern.


Assuntos
Síndrome de Imunodeficiência Adquirida , Anticolesterolemiantes , Infecções por HIV , HIV-1 , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Idoso , Anticolesterolemiantes/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Variação Biológica da População , Biomarcadores , HDL-Colesterol , LDL-Colesterol , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Humanos , Los Angeles , Masculino , Pessoa de Meia-Idade , Triglicerídeos
9.
Vasc Health Risk Manag ; 18: 555-566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898405

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent medications in the toolkit for treatment of atherosclerotic cardiovascular disease. These agents have been well studied in clinical trials supporting their efficacy in dramatically reducing low-density lipoprotein cholesterol (LDL-C) and impact on cardiovascular outcomes. Since the approval of commercial use for PCSK9 inhibitors in 2015, we have also gained significant experience in the use of these therapeutics in the real-world setting. In this article, we review current guideline recommendations, clinical trial evidence on efficacy and safety as well as data on cost-effectiveness, prescription and adherence. We focus primarily on the monoclonal antibody class of PCSK9 inhibitors in this review while also touching on other types of therapeutics that are under development.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Fatores de Risco
10.
Comput Math Methods Med ; 2022: 3369226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898474

RESUMO

Objective: To analyze the significance of ezetimibe in combination with low- to moderate-intensity atorvastatin adjuvant aspirin therapy for cerebrovascular disease. Methods: 110 patients with cerebrovascular disease treated in our hospital from June 2020 to June 2021 were selected and divided into 55 patients in the control group and 55 patients in the study group according to the lottery method. After a comprehensive examination, patients in the two groups should be given aspirin for treatment; the control group was treated with conventional dose of atorvastatin on top of the above, and the study group was given ezetimibe and medium-low-dose atorvastatin on top of aspirin treatment, activities of daily living (ADL) score, carotid artery intima-media thickness, lipid level, coagulation level, clinical effect, and adverse rate of the two groups which were tested and compared. Results: After treatment, ADL score, high-density leptin cholesterol (HDL-C), and ATIII levels increased, while carotid artery media thickness, triglyceride (TG), total cholesterol (TC), low-density leptin cholesterol (LDL-C), DD, PC, and hs-CRP levels decreased (P < 0.05). After treatment, ADL score, HDL-C, and ATIII levels were higher in the study group. The levels of carotid media thickness, TG, TC, LDL-C, DD, PC, and hs-CRP were significantly lower (P < 0.05). The clinical effect of the study group was outstanding (P < 0.05). The defect rate of the study group was lower than that of the control group, but there was no difference (P < 0.05). Conclusion: Ezetimibe combined with medium- and low-intensity atorvastatin with aspirin in the treatment of cerebrovascular diseases can effectively improve the coagulation function of patients, reduce the level of inflammatory factors in patients, and improve the level of blood lipids in patients, with high safety and worthy of clinical application.


Assuntos
Anticolesterolemiantes , Transtornos Cerebrovasculares , Atividades Cotidianas , Anticolesterolemiantes/efeitos adversos , Aspirina , Atorvastatina/uso terapêutico , Proteína C-Reativa , Espessura Intima-Media Carotídea , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Leptina , Pirróis , Resultado do Tratamento , Triglicerídeos
11.
Lancet ; 400(10349): 380-390, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35863366

RESUMO

BACKGROUND: Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. METHODS: In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. FINDINGS: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). INTERPRETATION: Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. FUNDING: Hanmi Pharmaceutical.


Assuntos
Anticolesterolemiantes , Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/efeitos adversos , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol , Quimioterapia Combinada , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Rosuvastatina Cálcica , Resultado do Tratamento
14.
Expert Opin Biol Ther ; 22(7): 813-820, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35698895

RESUMO

INTRODUCTION: Familial hypercholesterolemia is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) since birth and an exceedingly high risk of premature cardiovascular disease, especially in the homozygous form (HoFH). Despite the availability of effective cholesterol-lowering drugs, substantial LDL-C and cardiovascular risk reductions in these patients are still problematic, especially in those carrying mutations in the low-density lipoprotein receptor (LDLR) gene. AREAS COVERED: Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) encoding gene are associated with lower levels of LDL-C and reduced cardiovascular risk; the pharmacological inhibition of ANGPTL3 reduces LDL-C levels independently of LDLR. This approach can thus improve the treatment of HoFH using a monoclonal antibody targeting ANGPTL3 (evinacumab). EXPERT OPINION: Most lipid-lowering agents available so far are insufficient to achieve an appropriate response in HoFH patients. The inhibition of ANGPTL3 with evinacumab halves LDL-C levels in HoFH patients by an LDLR-independent mechanism. The results obtained so far have clearly indicated a promising improvement in the management of these patients. As the reduction of CV risk is proportional to the absolute reduction in LDL-C levels, we can expect that treatment with evinacumab, added to the maximally tolerated lipid-lowering therapy, will turn into a significant clinical benefit.


Assuntos
Anticorpos Monoclonais , Anticolesterolemiantes , Hipercolesterolemia Familiar Homozigota , Hiperlipoproteinemia Tipo II , Proteína 3 Semelhante a Angiopoietina , Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol , Hipercolesterolemia Familiar Homozigota/tratamento farmacológico , Humanos , Hiperlipoproteinemia Tipo II/tratamento farmacológico
15.
Adv Ther ; 39(8): 3578-3588, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689725

RESUMO

INTRODUCTION: There is little evidence on the relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and costs in patients on lipid-lowering therapy (LLT). We described healthcare resource use and costs (direct and indirect) by achieved LDL-C in patients receiving LLT after a recent myocardial infarction (MI) in Spain. METHODS: This was a retrospective observational study of anonymized electronic medical records from seven regions in Spain (BIG-PAC® database; n = 1.9 million). Eligible patients were adults (≥ 18 years) hospitalized for an MI between January 2015 and December 2017, treated with a statin and/or ezetimibe, and having recorded LDL-C values at baseline and during follow-up. Healthcare resource use and direct and indirect costs (in 2018, €) were described by achieved LDL-C levels during a follow-up of 18 months. RESULTS: Of 6025 patients (mean age, 69.7 years; 77% male), only 11% achieved LDL-C goals as defined in the 2016 ESC/EAS guidelines (< 70 mg/dL), and just 1% reached the lower target (< 55 mg/dL) in the current 2019 guidelines. Achieving lower LDL-C levels translated to lower healthcare resource use and costs. Mean total (direct and indirect) costs ranged from €5044 for patients with LDL-C < 55 mg/dL to €7567 for patients with LDL-C ≥ 130 mg/dL. CONCLUSION: Very few patients achieved recommended LDL-C goals despite using LLT. Achieving lower LDL-C levels after an MI might be associated with lower healthcare resource use and costs. Use of more intensive LLT, leading to greater reductions in LDL-C, could therefore be beneficial both from a clinical and an economic perspective.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Adulto , Idoso , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol , Atenção à Saúde , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Infarto do Miocárdio/tratamento farmacológico , Espanha , Resultado do Tratamento
16.
Curr Opin Lipidol ; 33(3): 147-159, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35695614

RESUMO

PURPOSE OF REVIEW: Lowering low-density lipoprotein cholesterol (LDL-C) with statins or ezetimibe reduces major adverse cardiovascular events (MACE) in patients with coronary heart disease. Additional treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may lower LDL-C to levels not achievable with conventional lipid-lowering agents. This review summarizes findings from two large, placebo-controlled trials that evaluated the cardiovascular efficacy of monoclonal antibodies directed against PCSK9, added to background statin therapy, in patients with established atherosclerotic cardiovascular disease (ASCVD) or recent acute coronary syndrome (ACS) and persistent elevation of atherogenic lipoproteins despite statin treatment. RECENT FINDINGS: The FOURIER trial with evolocumab and the ODYSSEY OUTCOMES trial with alirocumab demonstrated 15% overall reductions in MACE compared to placebo, associated with average achieved LDL-C levels as low as 30-40 mg/dl. Alirocumab treatment was associated with fewer deaths after ACS. Subgroups with large absolute treatment benefit included those with baseline LDL-C ≥100 mg/dl, diabetes, polyvascular or peripheral artery disease, prior coronary bypass surgery, statin intolerance, or elevated lipoprotein(a) levels. No safety concerns arose with use of PCSK9 monoclonal antibodies, even in patients who achieved LDL-C levels below 20 mg/dl. SUMMARY: In selected patients with established ASCVD or recent ACS, PCSK9 inhibitors can play an important role in reducing the risk of MACE, and may also reduce the risk of death after ACS.


Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Síndrome Coronariana Aguda/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Aterosclerose/tratamento farmacológico , LDL-Colesterol , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/uso terapêutico , Fatores de Risco , Subtilisinas/uso terapêutico
17.
Cardiol Rev ; 30(4): 214-219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35666780

RESUMO

Elevated plasma lipid levels, especially low-density lipoprotein, are correlated with atherosclerotic cardiovascular disease (ASCVD) and increased risk of ischemic heart disease and stroke. Statins are first-line agents for reducing low-density lipoprotein cholesterol (LDL-C) and the risk of major cardiovascular events, but patients with a genetic susceptibility or established ASCVD oftentimes remain subtherapeutic on statin therapy alone. Biotechnological advancements in medication therapy have led to the development of inclisiran, a recently approved twice-yearly injectable agent to help patients with heterozygous familial hypercholesterolemia and clinical ASCVD on a maximally tolerated statin to reach LDL-C targets. Inclisiran has demonstrated robust LDL-C reduction in clinical trials in combination with a favorable safety profile; however, the effect on cardiovascular clinical outcomes still remains under evaluation.


Assuntos
Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , LDL-Colesterol/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico
18.
G Ital Cardiol (Rome) ; 23(7): 481-490, 2022 Jul.
Artigo em Italiano | MEDLINE | ID: mdl-35771013

RESUMO

The last 50 years have experienced a rapid evolution in the development of lipid-lowering agents to reduce low-density lipoprotein cholesterol levels. This significant advance in medicine has not occurred without debate. Whether lowering blood cholesterol levels was beneficial has remained one of the most controversial issues during the past 50 years. The discovery of statins was the revolution that made it possible to delay and stop the progression of the atherosclerotic process resulting in improved health and longevity for millions of people. To date, statins remain the drugs of choice for the treatment of hypercholesterolemia. Despite their use, the risk of cardiovascular events persists. Therefore, the use of non-statin drugs, such as ezetimibe or PCSK9 inhibitors, in combination with statins has been shown to further reduce the risk of cardiovascular events. This review aims to summarize the advances in the field of lipid-lowering therapies over the past 50 years, focusing on advances in the development of drug therapies up to and including gene silencing or gene editing treatments that are expected in the near future.


Assuntos
Anticolesterolemiantes , Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperlipidemias , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Inativação Gênica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/genética , Hiperlipidemias/tratamento farmacológico , Pró-Proteína Convertase 9
19.
G Ital Cardiol (Rome) ; 23(7): 553-561, 2022 Jul.
Artigo em Italiano | MEDLINE | ID: mdl-35771021

RESUMO

BACKGROUND: Despite the availability of effective lipid-lowering drugs, only few high-risk patients attain their LDL cholesterol (LDL-C) guideline-recommended risk-based goal because of underprescription of combination therapy. We present an 18-month experience with variation of prescription protocols after publication of the 2019 ESC/EAS guidelines for the management of dyslipidemias. METHODS: Overall, 621 consecutive patients hospitalized for acute coronary syndrome at Mauriziano Hospital in Turin, Italy, between January 2020 and June 2021 were enrolled. Lipid-lowering therapy recommended at discharge was registered to evaluate how many patients received statin monotherapy, statin plus ezetimibe combination or triple therapy with high-intensity statin plus ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). At 6-month follow-up, the reduction in LDL-C, adverse events, compliance and cardiovascular recurrences was analyzed. RESULTS: Of 621 patients enrolled, 7 died during hospitalization. During the entire study period, 33% of patients received statin monotherapy, 50% were discharged on statin-ezetimibe combination, and PCSK9i (evolocumab) was prescribed to 17% of patients. Between April 2020 and June 2021, when new recommendations were introduced into clinical practice, 20% of patients received evolocumab, 56% combination therapy and only 24% were discharged on statin monotherapy. At the beginning of observation, evolocumab was prescribed to 3% of patients hospitalized for acute coronary syndrome, while at the end of the study period 27% of patients were discharged on PCSK9i, with an increase of the prescription rate by 759%; in the same period, prescription of statin monotherapy decreased by 75%. At 6-month follow-up, LDL-C reduction was 77% in patients treated with PCSK9i vs 48% in patients taking statin-ezetimibe combination therapy (p<0.001). All patients on evolocumab reached the guideline-directed goals and a low rate of adverse events was reported, mainly represented by local injection site reactions. Six patients experienced acute coronary syndrome recurrence; only one of them was treated with evolocumab. CONCLUSION: Prescription of intensive lipid-lowering therapy after acute coronary syndrome, eventually with introduction of PCSK9i during hospitalization or at discharge, leads to attainment of guideline-recommended goals for all patients, with a low incidence of adverse events and optimal compliance.


Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Coronariana Aguda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resultado do Tratamento
20.
Cardiovasc Diabetol ; 21(1): 107, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35706032

RESUMO

BACKGROUND: The Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. However, evidence of the optimal PCSK9 agents targeting PCSK9 for secondary prevention in patients with high-risk of cardiovascular events is lacking. Therefore, this study was conducted to evaluate the benefit and safety of different types of PCSK9 inhibitors. METHODS: Several databases including Cochrane Central, Ovid Medline, and Ovid Embase were searched from inception until March 30, 2022 without language restriction. Randomized controlled trials (RCTs) comparing administration of PCSK9 inhibitors with placebo or ezetimibe for secondary prevention of cardiovascular events in patients with statin-background therapy were identified. The primary efficacy outcome was all-cause mortality. The primary safety outcome was serious adverse events. RESULTS: Overall, nine trials totaling 54,311 patients were identified. Three types of PCSK9 inhibitors were evaluated. The use of alirocumab was associated with reductions in all-cause mortality compared with control (RR 0.83, 95% CrI 0.72-0.95). Moreover, evolocumab was associated with increased all-cause mortality compared with alirocumab (RR 1.26, 95% CrI 1.04-1.52). We also found alirocumab was associated with decreased risk of serious adverse events (RR 0.94, 95% CrI 0.90-0.99). CONCLUSIONS: In consideration of the fact that both PCSK9 monoclonal antibody and inclisiran enable patients to achieve recommended LDL-C target, the findings in this meta-analysis suggest that alirocumab might provide the optimal benefits regarding all-cause mortality with relatively lower SAE risks, and evolocumab might provide the optimal benefits regarding myocardial infarction for secondary prevention in patients with high-risk of cardiovascular events. Further head-to-head trials with longer follow-up and high methodologic quality are warranted to help inform subsequent guidelines for the management of these patients.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Humanos , Metanálise em Rede , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Prevenção Secundária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...