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1.
Vasc Health Risk Manag ; 17: 227-237, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054297

RESUMO

Despite widespread evidence of the effectiveness of lipid modification for the reduction of cardiovascular disease (CVD) risk, lipid modification goals are commonly underachieved in the United Kingdom (UK). In order to understand current UK lipid management guidance and the corresponding attainment of recommended lipid lowering goals relating to treatment with statins and ezetimibe, a literature review was conducted using PubMed focusing on publications between January 2017 and February 2020 in order to capture the most up-to-date literature. Identified publications were reviewed against key clinical guidelines for lipid management in relation to CVD risk from the National Institute for Health and Care Excellence (NICE, CG181), the Scottish Intercollegiate Guidelines Network (SIGN, 149) and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS). Cholesterol lowering goals are central to current lipid lowering therapy guidance, although specific goals vary depending on the guideline and patients' individual risk profile. Current guidance by NICE and SIGN specifies that treatment should achieve a greater than 40% reduction in non-high-density lipoprotein cholesterol (non-HDL-C) at 3 months of treatment, while the ESC/EAS place emphasis on the lowering of low-density lipoprotein (LDL-C) and total cholesterol. Yet, despite widespread availability of guidance and consistent messaging that lipid lowering goals should be ambitious, current evidence suggests a significant proportion of UK patients have sub-optimal reductions in cholesterol/non-HDL-C/LDL-C. The reasons for this are reported to be multifactorial, including a lack of compliance with guidelines, particularly regarding high-intensity statin prescribing, patient adherence, statin intolerance and statin reluctance as well as wider genetic factors. A number of possible strategies to improve current lipid management and attainment of lipid-lowering goals were identified, including improving the patient-healthcare professional partnership, conducting audits of local prescribing versus guidance, implementing plans for the refinement of current services and considering alternative options such as cost-effective single pill combinations for improving adherence.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Benchmarking , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Prevenção Primária , Medição de Risco , Fatores de Risco , Prevenção Secundária , Resultado do Tratamento , Reino Unido
2.
Expert Rev Clin Pharmacol ; 14(7): 793-806, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33970743

RESUMO

Introduction: Reducing low-density lipoprotein cholesterol (LDL-C) with lipid-lowering therapies has been associated with a decrease in the frequency of cardiovascular events.Areas covered: A systematic search was conducted on PubMed (MEDLINE), using the MeSH terms [Rosuvastatin] + [Ezetimibe] + [Dyslipidemia] + [treatment]. Original data from clinical trials, prospective and retrospective studies and more useful reviews were selected.Expert opinion: While statins continue to be the cornerstone of dyslipidemia management, many patients do not attain LDL-C targets with high-intensity statins alone. Rosuvastatin is a high-intensity statin with a low risk of adverse effects and drug-drug interactions and proven benefits in the prevention of cardiovascular disease. Rosuvastatin and ezetimibe have complementary mechanisms of action that enhance their ability to reduce LDL-C levels. Various studies have shown that the combination of rosuvastatin 10-40 mg and ezetimibe 10 mg enables considerable reductions in LDL-C (up to 60-75%) with a good safety profile in a broad spectrum of patients with hypercholesterolemia, including those at high risk and those with atherosclerotic cardiovascular disease. In addition, a fixed-dose combination of rosuvastatin and ezetimibe may improve adherence to medication. In this review, the available evidence on the combination of rosuvastatin and ezetimibe is updated.


Assuntos
Ezetimiba/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacologia , LDL-Colesterol/sangue , Combinação de Medicamentos , Ezetimiba/efeitos adversos , Ezetimiba/farmacologia , Fatores de Risco de Doenças Cardíacas , Humanos , Adesão à Medicação , Rosuvastatina Cálcica/efeitos adversos , Rosuvastatina Cálcica/farmacologia
3.
Endocrinol Diabetes Metab ; 4(2): e00221, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33855221

RESUMO

Background: Calcium oxalate stones are the most common cause of nephrolithiasis in the United States. Smaller studies of <15 patients investigating ezetimibe, a selective cholesterol absorption inhibitor, have suggested increased urine oxalate levels with use of the drug. We attempt to better define this relationship of ezetimibe on urinary oxalate using a larger patient sample analysing multiple urine collections on and off treatment. Materials and Methods: We retrospectively reviewed all consecutive patients from 01/2018 through 04/2019 evaluated for nephrolithiasis with use of ezetimibe documented in their medical record at Mayo Clinic Florida. Primary outcomes included increase in urinary oxalate with use of ezetimibe and reduction in urinary oxalate with discontinuation of medication. Results: Of 57 reviewed patients, 30 (53%) met inclusion criteria yielding 117 24-h urine measurements either on ezetimibe (72 measurements) or off ezetimibe (41 measurements). The mean urinary oxalate level off ezetimibe was 39.86 mg versus 40.45 mg with ezetimibe. After adjusting for age and sex, the estimated difference was 1.239 mg (95% CI, -4.856 to 7.335 mg; p = 0.93). A subset of six patients with urinary oxalate values both on and off ezetimibe showed a difference in 24-h urinary oxalate levels ranged from -16.40 to 14.95 mg (mean difference = 0.93 mg; median difference = 3.84 mg). Conclusion: Use of ezetimibe does not provide clear evidence of a difference in urinary oxalate levels.


Assuntos
Anticolesterolemiantes/efeitos adversos , Ezetimiba/efeitos adversos , Oxalatos/urina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Nefrolitíase/induzido quimicamente , Nefrolitíase/prevenção & controle , Nefrolitíase/urina , Estudos Retrospectivos
4.
Acta Diabetol ; 58(7): 949-957, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33745063

RESUMO

AIMS: Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of low-density lipoprotein cholesterol (LDL-C) that promotes a continuous inflammatory stimulus. Our aim was to evaluate the effect of PCSK9-i on inflammatory biomarkers, neutrophil-to-lymphocyte ratio, monocyte-to-high-density lipoprotein ratio (MHR), and on early atherosclerosis damage analyzed by pulse wave velocity (PWV) in a cohort of FH subjects. METHODS: In this prospective observational study, we evaluated 56 FH subjects on high-intensity statins plus ezetimibe and with an off-target LDL-C. All subjects were placed on PCSK9-i therapy and obtained biochemical analysis as well as PWV evaluation at baseline and after six months of PCSK9-i therapy. RESULTS: After six months of add-on PCSK9-i therapy, only 42.9% of FH subjects attained LDL-C targets. As expected, a significant reduction of LDL-C (- 49.61%, p < 0.001) was observed after PCSK9-i therapy. Neutrophil count (NC) and MHR were reduced by PCSK9-i (-13.82% and -10.47%, respectively, p value for both < 0.05) and PWV significantly decreased after PCSK9-i therapy (- 20.4%, p < 0.05). Finally, simple regression analyses showed that ∆ PWV was significantly associated with ∆ LDL-C (p < 0.01), ∆ NC and ∆ MHR (p value for both < 0.05). CONCLUSIONS: In conclusion, PCSK9-i therapy significantly improved lipid and inflammatory profiles and PWV values in FH subjects; our results support the positive effect of PCSK9-i in clinical practice.


Assuntos
Anticolesterolemiantes/farmacologia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/fisiopatologia , Idoso , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , HDL-Colesterol/sangue , Estudos de Coortes , Quimioterapia Combinada , Ezetimiba/administração & dosagem , Ezetimiba/efeitos adversos , Ezetimiba/farmacologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Itália , Contagem de Leucócitos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/patologia , Estudos Prospectivos , Análise de Onda de Pulso
5.
Atherosclerosis ; 320: 122-128, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33514449

RESUMO

BACKGROUND AND AIMS: Many patients with hypercholesterolemia fail to achieve sufficient low-density lipoprotein cholesterol (LDL-C) lowering despite use of guideline-recommended lipid-lowering therapies. This study evaluated LDL-C lowering with the combination of bempedoic acid, ezetimibe, and atorvastatin. METHODS: This was a phase 2, randomized, double-blind, placebo-controlled study (NCT03051100). After washout of lipid-lowering drugs, patients were randomized 2:1 to triple therapy (bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg; n = 43) or placebo (n = 20) once daily for 6 weeks. The primary endpoint was percent change from baseline in LDL-C at week 6. RESULTS: Mean age for the 63 randomized patients was 61.2 years; baseline LDL-C was 154.8 mg/dL. At week 6, mean LDL-C lowering with triple therapy (-63.6%) was significantly greater than with placebo [-3.1%; difference, -60.5% [(95% CI, -68.0% to -53.0%); p < 0.001]. Significant reductions with triple therapy vs. placebo were also observed for non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein (p < 0.001 for all). With triple-therapy, 90% of patients achieved LDL-C <70 mg/dL and 95% of patients had ≥50% lower LDL-C from baseline to week 6; no patients in the placebo group met either goal. The majority of treatment-emergent adverse events were mild to moderate in severity. No patients experienced clinically relevant elevations in aminotransferase or creatine kinase levels. CONCLUSIONS: Among patients with hypercholesterolemia, the combination of bempedoic acid, ezetimibe, and atorvastatin significantly lowered LDL-C, allowing more than 90% of patients in this study to reach guideline-recommended LDL-C goals.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Anticolesterolemiantes/efeitos adversos , Atorvastatina/efeitos adversos , Ácidos Dicarboxílicos , Método Duplo-Cego , Quimioterapia Combinada , Ezetimiba/efeitos adversos , Ácidos Graxos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamento farmacológico , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Clin Drug Investig ; 41(1): 19-28, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33368025

RESUMO

BACKGROUND AND OBJECTIVE: A limited number of trials have evaluated the efficacy of a fixed-dose combination of bempedoic acid and ezetimibe for the treatment of hypercholesterolemia. The aim of this meta-analysis of existing studies was to evaluate the efficacy and safety of fixed-dose bempedoic acid and ezetimibe combination therapy for the treatment of hypercholesterolemia. METHODS: A systematic literature search was conducted to identify randomized controlled trials (RCTs) comparing bempedoic acid and ezetimibe, versus placebo or ezetimibe alone, to 30 August 2020. A meta-analysis was conducted to investigate the efficacy of bempedoic acid and ezetimibe on lipid parameters and highly sensitive C-reactive protein (hsCRP) levels in patients with hypercholesterolemia or established atherosclerotic cardiovascular disease (ASCVD). Mean differences (MDs) or relative risk (RR) with their corresponding 95% confidence intervals (CIs), using random-effects models, were used to provide pooled estimates. RESULTS: A total of three phase II and III RCTs, comprising 388 patients, of whom 49.2% were treated with bempedoic acid and ezetimibe, and 197 controls, were identified. The duration of treatment was 12 weeks. Bempedoic acid and ezetimibe significantly reduced low-density lipoprotein cholesterol (MD - 29.14%, 95% CI - 39.52 to - 18.76; p < .001), total cholesterol (MD - 15.78%, 95% CI - 20.84 to - 10.72; p = 0.01), non-high-density lipoprotein cholesterol (MD - 18.36%, 95% CI - 24.60 to - 12.12; p = 0.01), and hsCRP levels (MD - 30.48%, 95% CI - 44.69 to - 16.28; p = 0.04). No significant effects on triglycerides (MD - 8.35%, 95% CI - 16.08 to - 0.63; p = 0.72) and improvement in high-density lipoprotein cholesterol (MD 1.63%, 95% CI - 4.03 to 7.28; p = 0.92) were observed with the fixed-dose combination therapy. Regarding safety, bempedoic acid and ezetimibe combination was associated with a non-significant increased risk of drug-related adverse events (RR 1.61, 95% CI 0.86-2.35) and overall adverse events (RR 1.16. 95% CI 0.97-1.35); however, the incidence of discontinuation of therapy (RR 0.75, 95% CI 0.35-1.49) was lower. CONCLUSION: This review found bempedoic acid and ezetimibe significantly lowered lipid parameters, attenuated hsCRP levels, and had an acceptable safety profile for the treatment of hypercholesterolemia and ASCVD.


Assuntos
Ácidos Dicarboxílicos/administração & dosagem , Ezetimiba/administração & dosagem , Ácidos Graxos/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/administração & dosagem , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Combinação de Medicamentos , Ezetimiba/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
7.
Eur J Clin Pharmacol ; 77(5): 747-755, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33215235

RESUMO

PURPOSE: Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. RESULTS: Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22-1.35) for statins, 1.09 (0.79-1.47) for ezetimibe, 1.38 (0.88-2.12) for fibrates, and 2.12 (1.31-3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64-0.74) for statins, 0.60 (0.41-0.86) for ezetimibe, 0.87 (0.51-1.42) for fibrates, and 1.21 (0.69-2.06) for resins. CONCLUSIONS: Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias.


Assuntos
Hipolipemiantes/efeitos adversos , Hiponatremia/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ezetimiba/efeitos adversos , Feminino , Ácidos Fíbricos/efeitos adversos , Nível de Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Socioeconômicos , Suécia/epidemiologia
8.
Cardiovasc J Afr ; 31(5): 245-251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33151240

RESUMO

BACKGROUND: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.8 and 3.5 mmol/l in patients with either very high cardiovascular risk or established atherosclerosis. In South Africa, there is a paucity of data on attainment of LDL-C goal in patients with very high cardiovascular risk who are on maximum tolerated statin with or without ezetimibe. OBJECTIVE: The aim was to assess the percentage of very high cardiovascular risk South African patients with dyslipidaemia not reaching an LDL-C goal of less than 1.8 mmol/l, despite maximum tolerated statin with or without ezetimibe. METHODS: This was a multi-centre, observational, cross-sectional study conducted at 15 private healthcare sector sites and one public sector site. Adults (> 18 years) with very high cardiovascular risk of familial hypercholesterolaemia receiving stable, maximum-tolerated statin therapy for at least four weeks prior to their latest lipid profile were enrolled into the study, and electronic case report forms were completed after written informed consent was provided. LDL-C goal attainment was modelled, first assuming an increase in the statin dose to the registered maximum, followed by the addition of ezetimibe or a PCSK9-inhibitor. RESULTS: In total, 507 patients were screened, of whom 492 were eligible for study participation. One patient was excluded from the analysis because of a missing LDL-C value. Most participants were male (male 329, 67%; female 162, 33%). Most patients were either obese (223, 46.0%) or overweight (176, 36.3%). Hypertension and diabetes mellitus were frequent co-morbidities and were found in 381 (77.6%) and 316 (64.4%) patients, respectively. Eighty (16.3%) patients reported current smoking. Only 68 (13.8%) patients were taking ezetimibe in addition to a statin. Reasons for not using ezetimibe included no requirement for ezetimibe in the opinion of the treating physician (229, 48.7%), cost (149, 31.7%), Physician's choice (39, 8.3%), or other (53, 11.3%). Only 161 (32.8%) of the patients attained their goal LDL-C level. In our modelling analysis, increasing the statin dose to the registered maximum and adding ezetimibe brought an additional 34.5% of patients to goal, while adding a PCSK9-inhibitor, irrespective of any other changes to lipid-lowering therapy brought over 90% of not-at-goal patients to goal. CONCLUSIONS: Most study participants were not at LDL-C goal despite maximum-tolerated statin, highlighting the need for treatment intensification in this high-risk population. Although intensifying treatment by adding a PCSK9-inhibitor brought more patients to goal, the initial addition of ezetimibe would be more reasonable, given the cost of PCSK9-inhibitors.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Comorbidade , Estudos Transversais , Regulação para Baixo , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Ezetimiba/efeitos adversos , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , África do Sul/epidemiologia , Fatores de Tempo , Resultado do Tratamento
9.
Expert Opin Pharmacother ; 21(17): 2137-2151, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32772741

RESUMO

INTRODUCTION: Statins are the first-line treatment to reduce cardiovascular (CV) events, mainly by reducing low-density-lipoprotein cholesterol (LDL-C), but many patients need additional treatments to reach the current lipid goals. AREAS COVERED: Herein, the authors review the published literature on the efficacy and safety of the therapies that are most often added to statins to achieve lipid targets. EXPERT OPINION: Ezetimibe is usually the first additional treatment to achieve LDL-C targets. It reduces LDL-C by about a further 20% and has an excellent safety and tolerability profile. The monoclonal antibody proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab, and alirocumab, can reduce LDL-C by ≥50% when added to statins and they also have a well-established safety and tolerability record. The recently approved bempedoic acid is well tolerated and appears to be free of skeletal muscle-related problems, but the CV outcome study with this drug has not been completed. Inclisiran, a small-interfering RNA targeting PCSK9 is at an advanced stage of development and the available data indicate a satisfactory safety profile and LDL-C lowering efficacy similar to the PCSK9 monoclonal antibodies with the advantage of less frequent administration.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , LDL-Colesterol/sangue , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Ezetimiba/administração & dosagem , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/sangue , Resultado do Tratamento
10.
Clin Investig Arterioscler ; 32(6): 231-241, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32605806

RESUMO

OBJECTIVE: To present the first registry used to analyse the clinical profile of patients treated with evolocumab in Spain, including the effectiveness on the lipid profile and safety in the «real world¼ setting. METHODS: Multicentre, retrospective, and observational study of patients starting treatment with evolocumab from February 2016 to May 2017 in clinical practice in Spanish cardiology units. RESULTS: A total of 186 patients (mean age 60.3 ± 9.8 years were included, 35.5% with familial hypercholesterolaemia, and 94.1% with a previous cardiovascular event) from 31 cardiology units. Baseline lipid profile: Total cholesterol 219.4 ± 52.2 mg/dL, LDL-cholesterol 144.0 ± 49.0mg/dL, HDL-cholesterol 47.7 ± 13.0mg/dL, and triglycerides 151.0 ± 76.2mg/dL. At the time of initiating evolocumab, 53.8% of patients were taking statins (50% had partial or total intolerance to statins), and 51.1% ezetimibe. In all cases, the dose of evolocumab used was 140 mg, mainly every 2 weeks (97.3%). Evolocumab compliance was high (92.3%). Treatment with evolocumab was interrupted in 6 patients (3.2%), with only 1 (0.5%) due to a probable side effect. Evolocumab significantly reduced total cholesterol (30.9% at week 2, and 39.3% at week 12; P<.001), LDL cholesterol (44.4% and 57.6%, respectively; P<.001), and triglycerides (14.8% and 5.2%, respectively; P<001), with no significant changes in HDL-cholesterol (6.7% and 2.0%; P=.14). CONCLUSIONS: In clinical practice, evolocumab is associated with reductions in LDL cholesterol, with nearly 60% after 12 weeks of treatment, and with low rates of interruptions due to side effects and high medication compliance. These results are consistent with those reported in randomised clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Sistema de Registros , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Serviço Hospitalar de Cardiologia/estatística & dados numéricos , Doenças Cardiovasculares/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Ezetimiba/efeitos adversos , Ezetimiba/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/prevenção & controle , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Estudos Retrospectivos , Prevenção Secundária , Espanha , Fatores de Tempo , Triglicerídeos/sangue
12.
Atherosclerosis ; 306: 33-40, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32683135

RESUMO

BACKGROUND AND AIMS: There is disquiet about statin effectiveness and side effects in both the medical and lay media. METHODS: We searched the literature for reports on the incidence of statin intolerance (SI) in which control rates of similar events were also recorded. The number of people who must receive treatment (NNT) to prevent one atherosclerotic cardiovascular disease (ASCVD) event at 5-50% 10-year risk and LDL cholesterol 2-7 mmol/l was compared with the number of those who would experience harm attributable to statin (NNH). Using a similar method, the effectiveness of various strategies to overcome SI in preventing CVD was then compared. RESULTS: Observational studies with non-randomised control groups report higher rates of statin adverse events than randomised trials. Overall, at least 75 patients must be treated for one to experience a side effect. In contrast, the NNT to prevent one ASCVD event with statins as monotherapy or in combination with other cholesterol-lowering medications to achieve at least 50% decrease in LDL cholesterol and <1.8 mmol/l was between 3 and 61, depending on risk and LDL cholesterol. NNH for adverse events of severity equivalent to ASCVD was >750 (<0.1333%). When SI is encountered, the most effective current management for most patients in terms of ASCVD reduction is to rechallenge with low dose potent statin and then up-titrate until the cholesterol target has been achieved with, if necessary, the addition of ezetimibe 10 mg daily. CONCLUSIONS: The most severe complication of SI is discontinuation of effective cholesterol-lowering treatment in patients who, by virtue of their CVD risk and cholesterol level, might otherwise benefit.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Colesterol , LDL-Colesterol , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos
13.
Circulation ; 142(8): 748-757, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32594766

RESUMO

BACKGROUND: The TST trial (Treat Stroke to Target) showed the benefit of targeting a low-density lipoprotein cholesterol (LDL-C) concentration of <70 mg/dL in terms of reducing the risk of major cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature. The impact on carotid atherosclerosis evolution is not known. METHODS: TST-PLUS (Treat Stroke to Target-Plaque Ultrasound Study) included 201 patients assigned to an LDL-C concentration of <70 mg/dL and 212 patients assigned to a target of 100±10 mg/dL. To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe as needed. Ultrasonographers were certified and carotid ultrasound examinations were performed using M'Ath software at baseline and at 2, 3, and 5 years. All images were uploaded to the Intelligence in Medical Technologies database directly from the carotid ultrasound device. The central core laboratory performed all offline measurements of the intima-media thickness of both common carotid arteries blinded from the randomization arm. The main outcomes were newly diagnosed atherosclerotic plaque on carotid bifurcation or internal carotid artery using the Mannheim consensus definition and between-group comparison of common carotid arteries intima-media thickness change. RESULTS: After a median follow-up of 3.1 years, the achieved LDL-C concentrations were 64 mg/dL (1.64 mmol/L) in the lower-target group and 106 mg/dL (2.72 mmol/L) in the higher-target group. Compared with the higher-target group, patients in the lower-target group had a similar incidence of newly diagnosed carotid plaque: 46/201 (5-year rate, 26.1%) versus 45/212 (5-year rate, 29.7%). The change in common carotid arteries intima-media thickness was -2.69 µm (95% CI, -6.55 to 1.18) in the higher-target group and -10.53 µm (95% CI, -14.21 to -6.85) in the lower-target group, resulting in an absolute between-group difference of -7.84 µm (95% CI, -13.18 to -2.51; P=0.004). CONCLUSIONS: In patients with ischemic stroke and atherosclerosis, an LDL-C target of <70 mg/dL (1.8 mmol/L) did not reduce the incidence of new carotid plaques but produced significantly greater regression of carotid atherosclerosis than an LDL-C target of 90 to 110 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.


Assuntos
Doenças das Artérias Carótidas , LDL-Colesterol/sangue , Ezetimiba/administração & dosagem , AVC Isquêmico , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/tratamento farmacológico , Ezetimiba/efeitos adversos , Feminino , Seguimentos , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , AVC Isquêmico/prevenção & controle , Masculino , Pessoa de Meia-Idade , Ultrassonografia
14.
Biomed Pharmacother ; 129: 110388, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32559626

RESUMO

Statin therapy is the gold standard in the treatment of dyslipidemia. Understanding the mechanisms of action of these drugs provides an opportunity to define new therapeutic goals for pharmacotherapy in patients with atherosclerotic lesions. The present review indicates the existence of previously unknown therapeutic targets for statins, such as Krüppel-like Factor 2 (KLF-2), Cystathionine γ lyase (CSE) and the microRNA regulating eNOS activity and synthesis; nuclear PXR receptor and EB transcription factor regulating Inflammasome NLRP3 activity; the Dickkopf-related protein 1 (DKK-1), which inhibits the WNT signalling pathway; the peroxisome proliferator-activated receptor (PPAR-γ) in vascular smooth muscle cells (VSMCs), which regulates the cell cycle, and the ERK5-Nrf2 pathway, which reduces the level of harmful advanced glycation end-products (AGE) in VSMCs during diabetic vasculopathy. Importantly, our review includes a number of promising discoveries, specifically those related to the effects of miR-221, miR-222 and miR-27b on the structure, synthesis and activity of eNOS, such as microRNA-based therapies, which offer promise in future targeted therapies. In contrast to numerous experiments confirming the pleiotropic effect of statins, there is still insufficient evidence on the pleiotropic effect of ezetimibe, which goes beyond its basic inhibitory effect on intestinal cholesterol absorption. However, recent studies indicate that this effect is limited to inhibiting macrophage migration, decreasing VCAM-1 expression and reducing the levels of reactive oxygen species. Defining new therapeutic goals for pharmacotherapy in patients with atherosclerotic lesions and ensuring effective treatment of dyslipidemia and its associated cardiovascular complications requires a thorough understanding of both the mechanisms of action of these drugs and of atherosclerosis itself.


Assuntos
Aterosclerose/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Dislipidemias/diagnóstico , Dislipidemias/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Transdução de Sinais
15.
J Cardiovasc Pharmacol Ther ; 25(6): 548-555, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32567339

RESUMO

BACKGROUND: Controversy remains regarding the influence of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio. OBJECTIVE: This study aimed to clarify the effects of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio in patients with acute coronary syndrome (ACS). METHODS: This was a post hoc sub-analysis of the Heart Institute of Japan-PRoper level of lipid-lowering with pitavastatin and ezetimibe in ACS study. We compared the eicosapentaenoic acid/arachidonic acid ratio changes from baseline to the 3-month follow-up after contemporary lipid-lowering therapy with pitavastatin + ezetimibe therapy and pitavastatin mono-therapy. RESULTS: Among patients with ACS and dyslipidemia, the eicosapentaenoic acid/arachidonic acid increased significantly in the pitavastatin mono-therapy group (0.40 ± 0.26 to 0.46 ± 0.34, P < .0001) but did not increase in the pitavastatin + ezetimibe group (0.37 ± 0.22 to 0.38 ± 0.27, P = .18). When the analysis was limited to patients who received 2 mg/day of pitavastatin during the follow-up period, these trends in changes of the eicosapentaenoic acid/arachidonic acid ratio remained unchanged. Multivariate analysis showed that ezetimibe use (P = .005; ß = 0.09), ST-elevation myocardial infarction (P = .04; ß = -0.01), and baseline low-density lipoprotein cholesterol (LDL-C) level (P = .0003; ß = 0.12) were independent predictors of the percentage change in the eicosapentaenoic acid/arachidonic acid ratio. These trends were similar even when the analysis was limited to patients who did not take statins at enrollment. CONCLUSION: Standard lipid-lowering therapy with pitavastatin mono-therapy improved the eicosapentaenoic acid/arachidonic acid ratio for patients with ACS. Intensive lipid-lowering therapy with pitavastatin + ezetimibe did not improve the eicosapentaenoic acid/arachidonic acid ratio, although LDL-C decreased significantly. Inhibition of the improvement in the eicosapentaenoic acid/arachidonic acid ratio by adding ezetimibe may affect cardiovascular disease prognosis.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Ácido Araquidônico/sangue , Ácido Eicosapentaenoico/sangue , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Quinolinas/uso terapêutico , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Idoso , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Ezetimiba/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
J Cardiovasc Transl Res ; 13(6): 900-907, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32367340

RESUMO

We compared the effects of ezetimibe/rosuvastatin 10/5 mg versus rosuvastatin 20 mg on carotid atherosclerotic plaque inflammation measured by 18FDG PET/CT. Fifty patients with acute coronary syndrome (ACS) were randomly assigned to the ezetimibe/rosuvastatin 10/5 mg and rosuvastatin 20 mg groups. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS), as assessed by 18FDG PET/CT at baseline and at 6 months. Forty-eight patients completed follow-up PET/CT. MDS TBR was - 6.2 ± 13.9% for patients in the ezetimibe/rosuvastatin group and - 10.8 ± 17.7% for those in the rosuvastatin group (difference, 4.6 percentage points; upper limitation of one-sided confidence interval = 13.8; p = 0.60 for noninferiority). In conclusion, combination therapy with ezetimibe 10 mg and rosuvastatin 5 mg compared with rosuvastatin 20 mg did not meet the criterion for non-inferiority for primary outcome, and the present study was not conclusive on whether the former was non-inferior to the latter. Graphical Abstract.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Anticolesterolemiantes/administração & dosagem , Doenças das Artérias Carótidas/tratamento farmacológico , Ezetimiba/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Placa Aterosclerótica , Rosuvastatina Cálcica/administração & dosagem , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Anti-Inflamatórios/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Doenças das Artérias Carótidas/diagnóstico por imagem , Combinação de Medicamentos , Ezetimiba/efeitos adversos , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Rosuvastatina Cálcica/efeitos adversos , Seul , Fatores de Tempo , Resultado do Tratamento
17.
J Cardiovasc Pharmacol Ther ; 25(5): 409-417, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32419478

RESUMO

BACKGROUND: Previous meta-analyses have shown that statins may cause incident diabetes. This article reviews randomized controlled trials using proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) or ezetimibe on the risk of new-onset diabetes. METHODS: Eight trials involving PCSK9i and 3 trials of ezetimibe were selected for review. PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were thoroughly searched for relevant trials. Inclusion criteria included at least 100 patients per treatment arm, follow-up of at least 52 weeks, and at least double-blinded study design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized, placebo-controlled, open-label, and crossover trials. The primary outcome was the number of incident diabetes cases. A random effects model was used. Heterogeneity in effect sizes was measured with I 2 parameter and the Q statistic was used to test for excessive between-study heterogeneity. RESULTS: A total of 52 214 participants for the PCSK9i and a total of 20 084 for the ezetimibe meta-analyses were included. Participants randomized to PCSK9i did not differ from the control patients in diabetes incidence (risk ratio [RR] = 0.99, P = .87, 95% CI = 0.92-1.07). Participants randomized to ezetimibe did not differ from the control patients in diabetes incidence (RR = 1.05, P = .37, 95% CI = 0.95-1.15). DISCUSSION: The use of PCSK9i and ezetimibe does not appear to impact the risk of incident diabetes mellitus when added to guideline-directed medical therapy.


Assuntos
Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus/epidemiologia , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Inibidores de Serino Proteinase/uso terapêutico , Anticolesterolemiantes/efeitos adversos , Diabetes Mellitus/diagnóstico , Método Duplo-Cego , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Ezetimiba/efeitos adversos , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
18.
Lancet Gastroenterol Hepatol ; 5(7): 649-657, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389183

RESUMO

BACKGROUND: An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors. METHODS: HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing. FINDINGS: 30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log10IU/mL (IQR 4·55-5·63) and at least three HCV genotypes were represented (nine [50%] donors with genotype 1, two [11%] with genotype 2, five [28%] with genotype 3, and two [11%] with unknown genotype). All 30 (100%) transplant recipients met the primary endpoint of undetectable HCV RNA at 12 weeks post-transplant, and were HCV RNA-negative at last follow-up (median 36 weeks post-transplant [IQR 25-47]). Low-level viraemia was transiently detectable in 21 (67%) of 30 recipients in the early post-transplant period but not after day 14. Treatment was well tolerated with no dose reductions or treatment discontinuations; 32 serious adverse events occurred in 20 (67%) recipients, with one grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment. Non-serious transient elevations in ALT and creatine kinase during the study dosing period resolved with treatment completion. Among the serious adverse events were two recipient deaths due to causes unrelated to study drug treatment (sepsis at 49 days and subarachnoid haemorrhage at 109 days post-transplant), with neither patient ever being viraemic for HCV. INTERPRETATION: Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors. FUNDING: Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ezetimiba/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/prevenção & controle , Adulto , Idoso , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Canadá/epidemiologia , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Ezetimiba/administração & dosagem , Ezetimiba/efeitos adversos , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Quinoxalinas/administração & dosagem , Quinoxalinas/efeitos adversos , Quinoxalinas/uso terapêutico , Vírus de RNA/genética , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Transplantes/virologia , Carga Viral/estatística & dados numéricos
19.
Clin Pharmacol Ther ; 108(4): 833-843, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32320058

RESUMO

The efficacy and safety of statin and ezetimibe combination therapy in patients with chronic kidney disease (CKD) remains unclear. To assess the effect of statin and ezetimibe combination therapy on controlling lipid profiles and reducing cardiovascular events in patients with CKD, we conducted a systematic review and meta-analysis. We selected randomized controlled trials comparing this combination therapy with statin monotherapy or placebo in patients with CKD from the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases published before September 1, 2018 on the Internet. Eight articles on seven studies, with a total of 14,016 patients with CKD, were selected from 412 full-text articles. Statin and ezetimibe combination therapy had beneficial effects on serum total cholesterol (weighted mean difference (WMD) -20.31 mg/dL, 95% confidence interval (CI), -26.87 to -13.75 mg/dL, P < 0.001), low-density lipoprotein cholesterol (WMD -17.22 mg/dL, 95% CI, -18.93 to -15.51 mg/dL, P < 0.001), and triglycerides (WMD -15.08 mg/dL, 95% CI, -23.41 to -6.75 mg/dL, P < 0.001) compared with statin monotherapy. Statin and ezetimibe combination therapy significantly reduced all-cause mortality and major adverse cardiovascular events (risk ratio 0.86, 95% CI, 0.77 to 0.97, P = 0.01). The incidence of adverse events was low, with no significant difference between statin and ezetimibe combination therapy and statin monotherapy. In conclusion, the statin and ezetimibe combination therapy significantly improved serum lipid profiles and reduced risks of all-cause deaths and major adverse cardiovascular events compared with the control group in patients with CKD.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Rim/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Combinação de Medicamentos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/mortalidade , Ezetimiba/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Clin Lipidol ; 14(1): 88-97.e2, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32192644

RESUMO

BACKGROUND: The 24-week randomized, double-blind ODYSSEY ALTERNATIVE trial (NCT01709513) demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 inhibitor alirocumab vs ezetimibe in statin-intolerant patients, with significantly fewer skeletal muscle events (SMEs; 32.5%) vs atorvastatin (46.0%; hazard ratio: 0.61, 95% confidence interval: 0.38 to 0.99, P = .042). OBJECTIVE: ALTERNATIVE participants could enter an open-label treatment period (OLTP) for assessment of long-term safety. METHODS: Two hundred and eighty one patients entered the OLTP; 93.7%, 84.0%, and 92.9% of patients who received atorvastatin, ezetimibe, and alirocumab, respectively, during double-blind treatment, including 216 patients (76.9%) who completed double-blind treatment, as well as patients who either prematurely discontinued treatment due to SME (n = 51 [18.1%]) or other reasons (n = 14 [5.0%]) but completed week 24 assessments. All patients in the OLTP received alirocumab (75 or 150 mg every 2 weeks based on investigator decision) for ∼3 years or until commercial availability, whichever came first. RESULTS: SMEs were reported by 38.4% of patients in the OLTP. Safety results from the OLTP were similar to those of the alirocumab group in the double-blind period, except for a lower rate of discontinuations due to SMEs observed with alirocumab in the OLTP (3.2% vs 15.9% in the double-blind period). At OLTP week 8, mean LDL-C reduction from baseline (=week 0 of double-blind period) was 52.0%, with reductions sustained through to the end-of-treatment visits (55.4% and 53.7% reduction at weeks 100 and 148, respectively). CONCLUSIONS: In this population of statin-intolerant patients, alirocumab was well tolerated and produced durable LDL-C reductions over 3 years.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/genética , Idoso , Atorvastatina/administração & dosagem , Atorvastatina/efeitos adversos , LDL-Colesterol/efeitos dos fármacos , Método Duplo-Cego , Ezetimiba/administração & dosagem , Ezetimiba/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia
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