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1.
Medicine (Baltimore) ; 98(32): e16646, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393363

RESUMO

To examine whether the Medicare Part D program had an impact on the generic drug prescription rate among residents in long-term care facilities.We analyzed prescription data for 3 drug classes (atypical antipsychotic, proton pump inhibitor, and statin) obtained from a regional online pharmacy serving long-term care centers in Pennsylvania from January 2004 to December 2007.Difference-in-difference is used as a primary analysis method, and different regression methods (probit and multinomial) are used to accommodate different types of outcome measures.Contrary to expectations, the Part D program did not have a statistically significant impact on the generic prescription rate in the long-term care setting during the study period. Only the statin class showed a dramatic increase in generic drug prescriptions, mainly due to the loss of patent protection for one of the most popular brand-name drugs in the class.The complex dynamics of the prescription drug market, particularly the availability of generic versions of popular prescription medications, had a bigger role in increasing the prescription rate of generic drugs than the Part D program. This warrants the need to relax prescription medicines' patent policies and for further study on the impact of such policies.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Medicamentos Genéricos , Seguro de Serviços Farmacêuticos/estatística & dados numéricos , Medicare Part D/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos , Estudos de Casos e Controles , Prescrições de Medicamentos/classificação , Substituição de Medicamentos , Revisão de Uso de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Assistência de Longa Duração/estatística & dados numéricos , Masculino , Inibidores da Bomba de Prótons , Estados Unidos
2.
Klin Lab Diagn ; 64(7): 388-396, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31408589

RESUMO

Inhibition of hydrolysis of palmitic and oleic triglycedires (TG) in very low density lipoproteins (VLDL), slow formation of active apoВ-100 conformation, blockade of апоЕ/В-100 ligand formation in VLDL and their reduced uptake by insulin-dependent cells cause hypertriglyceridemia (HTG). Palmitic and oleic VLDL (>80% total VLDL) are not converted in low density lipoproteins (LDL). Atherosclerosis is not an alimentary deficiency of polyenic fatty acids (PFA), but results from low in vivo bioavailability of PFA in LDL against the background of high dietary palmitic FA and palmitic LDL. Plasma PFA content and cellular PFA deficiency are as high as LDL cholesterol (CL). Primary prevention of atherosclerosis should be based on a decrease in dietary content of palmitic saturated FA, trans FA and a moderate increase in PFA. It seems highly unlikely that the xeobiotics statins, fibrates and probucol produce pleiotropic biological effects in vivo. These effects are brought about by phylogenetically early humoral mediators eicosanoids: prostacyclins, prostaglandins, thromboxanes, leukotrienes, and resolvins. It is reasonable to suggest that all preparations which act according to the same algorithm activate TG hydrolysis in VLDL and normalize cellular uptake of PFA in linoleic and linolenic LDL via apoВ-100 endocytosis. Atherosclerosis is a syndrome of cellular deficiency of essential polyenic FA.


Assuntos
Dieta , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertrigliceridemia/patologia , Lipólise , Lipoproteínas VLDL/metabolismo , Ácidos Graxos/sangue , Ácidos Fíbricos/farmacologia , Humanos , Triglicerídeos
4.
Medicine (Baltimore) ; 98(34): e16931, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441882

RESUMO

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94-0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45-1.62), 0.63 (95% CI, 0.57-0.71), and 0.34 (95% CI, 0.30-0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.


Assuntos
Cognição/efeitos dos fármacos , Demência/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Demência/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologia
5.
Medicine (Baltimore) ; 98(29): e16480, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335710

RESUMO

Whether statin use has any impact on survival of esophageal cancer patients remains controversial. Therefore, we conducted a meta-analysis focusing on current topic for the first time.We systematically searched the following databases for relevant studies comparing survival between statin users and non-users among esophageal cancer patients up to March 16, 2019: Pubmed, Embase, and Web of Science. We extracted data of hazard ratio (HR) with 95%confidence interval (CI) of all-cause and cancer-specific mortality for analysis. We used the STATA 12.0 software to perform this meta-analysis.We finally included a total of 4 cohort studies involving a total of 20,435 esophageal cancer patients (5319 statin users and 15116 non-users). Our meta-analysis found that statin use after diagnosis of esophageal cancer was significantly correlated to decreased all-cause (random effects: HR = 0.81, 95%CI: 0.75-0.89, P < .001; I = 68.1%) and cancer-specific mortality (fixed effects: HR = 0.84, 95%CI: 0.78-0.89, P < .001; I = 46.6%) in esophageal cancer patients. When stratified by pathological subtypes, the protective effect of statin use after diagnosis of esophageal cancer was observed in both esophageal adenocarcinoma patients and esophageal squamous cell carcinoma patients. Moreover, statin use before diagnosis of esophageal cancer was also confirmed to have favorable survival benefit for esophageal cancer patients.Statin use was significantly correlated to lower mortality risk of esophageal cancer patients regardless of the time when statins were taken and pathological subtypes of esophageal cancer. Statins may serve as promising adjunctive anticancer agents for treating esophageal cancer.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Causas de Morte , Humanos , Modelos de Riscos Proporcionais , Análise de Sobrevida
6.
Int J Cardiovasc Imaging ; 35(9): 1745-1753, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312997

RESUMO

No data exist whether statins have robust anti-inflammatory effects of atherosclerotic plaques primarily during the early treatment period or continuously throughout use. This prospective three time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study of the carotid artery assessed anti-inflammatory effects of statin during the early treatment period (initiation to 3 months) and late treatment period (3 months to 1 year) and their correlation with lipid and inflammatory profile changes during a year of therapy. Nine statin-naïve stable angina patients with inflammatory carotid plaques received 20 mg/day atorvastatin after undergoing initial 18F-FDG PET/CT scanning of carotid arteries and ascending thoracic aorta, and then completed serial 18F-FDG PET/CT imaging at 3 and 12 months whose data were analyzed. The primary outcome was the inter-scan percent change in target-to-background ratio (ΔTBR) within the index vessel. At 3 months of atorvastatin treatment, mean serum low-density lipoprotein cholesterol (LDL-C) level decreased by 36.4% to < 70 mg/dL (p = 0.001) and mean serum high-density lipoprotein cholesterol level increased to > 40 mg/dL (p = 0.041), with both maintained with no further reduction up to 1 year (p = 0.516 and 0.715, respectively) while mean serum high sensitivity C-reactive protein level only numerically decreased (p = 0.093). The index vessel ΔTBR showed continuous plaque inflammation reduction over 1 year, by 4.4% (p = 0.015) from the initiation to 3rd months and 6.2% (p = 0.009) from 3rd months to 1 year, respectively, without correlation with lipid profile changes. The ΔTBR of the bilateral carotid arteries and ascending aorta also continuously decreased from 3 months to 1 year. Three time point 18F-FDG PET/CT imaging demonstrates that statin's anti-inflammatory effect continues throughout its use up to 1 year, even though yielding stable below-target plasma LDL-C levels at 3 months.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/tratamento farmacológico , Fluordesoxiglucose F18/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
8.
Einstein (Sao Paulo) ; 17(3): eAO4399, 2019 May 30.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31166482

RESUMO

OBJECTIVE: To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay. METHODS: Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study. RESULTS: Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease. CONCLUSION: Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.


Assuntos
Lesão Renal Aguda/terapia , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/efeitos dos fármacos , Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Terapia de Substituição Renal/estatística & dados numéricos , Triglicerídeos , APACHE , Lesão Renal Aguda/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Creatinina/sangue , Cuidados Críticos/métodos , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Valores de Referência , Terapia de Substituição Renal/mortalidade , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue , Adulto Jovem
9.
Yonsei Med J ; 60(7): 679-686, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31250582

RESUMO

PURPOSE: Statins, metformin, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) have been suggested for treating age-related macular degeneration (AMD) due to their pleiotropic effects. Therefore, we investigated whether these drugs prevent AMD. MATERIALS AND METHODS: We conducted a nested case-control study using the Korean National Health Insurance Service database. Using risk-set sampling of age, sex, cohort entry date, and follow-up duration, we identified incident patients with AMD and 10 matching controls in cohorts with diabetes mellitus or cardiovascular diseases. Exposure was assessed within one year before the index date using patient prescription records. We conducted conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between cardiovascular medications and AMD. RESULTS: Our study included 2330 cases and 23278 controls from a cohort of 231274 patients. The ORs (95% CI) for AMD occurrence in users prescribed with statins, metformin, ACE inhibitors, and ARBs were 1.12 (0.94-1.32), 1.15 (0.91-1.45), 0.90 (0.61-1.34), and 1.21 (1.05-1.39), respectively. A duration-response was not observed. CONCLUSION: Statins, metformin, ACE inhibitors, and ARBs did not inhibit AMD in elderly patients. The absence of a duration-response supports the lack of a causal relationship.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Degeneração Macular/tratamento farmacológico , Metformina/farmacologia , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Modelos Logísticos , Masculino , Metformina/uso terapêutico
10.
Kardiologiia ; 59(5S): 4-12, 2019 Jun 19.
Artigo em Russo | MEDLINE | ID: mdl-31221071

RESUMO

Statins are widely prescribed and the risk of adverse drug reactions of lipid-lowering therapy is actively discussed, including muscle symptoms. This review synthesizes the knowledge about the clinical aspects of statin-associated muscle symptoms, which is important for the practitioner. Potential mechanisms of their development, risk factors, clinical manifestations, treatment and prevention are described. Timely detection the side effects of statins makes it possible to diagnose and eliminate, which is crucial for conducting lipid-lowering therapy for patients with atherosclerotic cardiovascular diseases. Management of statin-associated muscle symptoms requires altering (reduced dosages, use of another statin or alternative lipid-lowering drugs) or discontinuing the statin treatment.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Humanos , Hipolipemiantes , Músculo Esquelético , Fatores de Risco
11.
Kardiologiia ; 59(5S): 13-26, 2019 Jun 20.
Artigo em Russo | MEDLINE | ID: mdl-31221072

RESUMO

This study focused on analysis of current publications evaluating safety of lipid-lowering therapy. Search for literature was performed on websites of cardiological societies and online databases, including PubMed, EMBASE, and eLibrary by the following key words: statins, statin intolerance, lipid-lowering therapy, statin safety, and statin аdverse effects. The focus is on statins, in view of the fact that they are the most commonly prescribed, highly effective and safe drugs for primary and secondary cardiovascular prophylaxis. This review consistently summarized information about myopathies, hepatic and renal dysfunction, potentiation of DM, and other possible adverse effects of lipid-lowering therapy. The author concluded that despite the high safety of statins acknowledged by all international cardiological societies, practicing doctors still continue unreasonably cancel statins, exposing the patient under even greater danger. Information about the corresponding author.


Assuntos
Lipídeos/análise , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases
12.
Kardiologiia ; 59(5S): 47-57, 2019 Jun 20.
Artigo em Russo | MEDLINE | ID: mdl-31221075

RESUMO

This Conclusion of the Board of experts is devoted to the analysis of the evidence base, the position in modern clinical guidelines, the efficacy and safety analysis as well as the options of combined therapy with statins and ezetimibe (Otrio, JSC "AKRIKHIN") in various categories of patients in routine clinical practice in theRussian Federation. Cardiovascular diseases (CVD) continue to lead in the structure of morbidity and mortality inRussia. Hypercholesterolemia is one of the main modifiable risk factors for CVD. Administration of HMGCo-A-reductase inhibitors (statins) remains the basis for the prevention and treatment of the main complications of atherosclerosis, but the achievement of target levels of LDL-C on of statin monotherapy in Russian practice among different categories of risk does not exceed 50%. Proportion of patients (up to 12%) does not tolerate statin therapy, which requires the search for alternative therapies. To optimize the control of the level of LDL-C, combination therapy with statins and ezetimibe is used. Ezetimibe is an effective lipid-lowering drug, an inhibitor of intestinal absorption of cholesterol, which was investigated in many international and Russian studies, the results of which have demonstrated good tolerability, safety and efficacy (reduction of LDL-C levels by 18% in monotherapy). It was noted that the combined therapy with low/medium doses of statins and ezetimibe effectively reduces the level of LDL-C by 44-53%, which is comparable to the effect of high doses of statins and reduces CV risk in patients with CKD and ACS. Otrio (INN Ezetimib) tablets 10 mg ( JSC "AKRIKHIN",Russia) has demonstrated bioequivalence to the original drug Ezetrol tablets 10 mg (Schering-plough Labo N. V,Belgium). Broad use of a new generic product Otrio in combination with different statins will significantly increase the frequency of achievement of target lipid levels in patients with high and very high CV risk, including patients with chronic renal failure, type 2 diabetes and in patients with high hypercholesterolemia (LDL-C > 5 mmol/l) and, ultimately, reduce the burden of CV disease and mortality in Russia.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Anticolesterolemiantes , LDL-Colesterol , Quimioterapia Combinada , Ezetimiba , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Metabolismo dos Lipídeos , Fatores de Risco , Federação Russa
13.
Medicine (Baltimore) ; 98(20): e15484, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096447

RESUMO

INTRODUCTION: The purpose of this study protocol is to provide the methodology for a review to compare the effect of statins vs physical exercise interventions and the effect of different types of physical exercise, on reducing arterial stiffness associated with cardiovascular diseases and mortality. METHODS AND ANALYSIS: The literature search will be conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception until July 31, 2019. We will include randomized controlled trials, nonrandomized experimental studies, and controlled pre-post studies assessing the effect in the general population of statins and physical exercise interventions on arterial stiffness measured by pulse wave velocity. The Cochrane Collaboration's tool and the Quality Assessment Tool for Quantitative Studies will be used to assess the risk of bias for studies included in the systematic review. A Bayesian network meta-analysis will be carried out to determine the comparative effect of the different physical exercise interventions and/or statin intervention. ETHICS AND DISSEMINATION: This study will generate evidence about the effectiveness of both statins and exercise on reducing arterial stiffness that potentially can be transferred to patients and practitioners. Moreover, in light of the importance of reducing arterial stiffness for preventing cardiovascular disease, the evidence provided by this study will be potentially suitable to be included in cardiovascular clinical practice guidelines. STRENGTHS AND LIMITATIONS: This protocol describes the methods of a study examining, using network meta-analysis strategies, the efficacy of statins and different types of exercise on improving arterial stiffness, which is an early marker of atherosclerosis. The results of this study could immediately help clinicians to recommend the best evidence-based intervention to their patients to reduce arterial stiffness and, as a consequence, prevent major complications, such as heart failure, stroke, or myocardial infarction. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019123120.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Exercício/fisiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Rigidez Vascular/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Meta-Análise em Rede , Ensaios Clínicos Controlados não Aleatórios como Assunto , Avaliação de Resultados (Cuidados de Saúde) , Análise de Onda de Pulso/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Rigidez Vascular/fisiologia
14.
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
16.
Methodist Debakey Cardiovasc J ; 15(1): 23-31, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049146

RESUMO

The discovery of statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) is a consequence of the highly targeted, arduous search for naturally occurring compounds that inhibit cholesterol biosynthesis. An enormous amount of basic scientific, genetic, and clinical research substantiated the role of lipoprotein-derived cholesterol in atherogenesis. Quantifying the impact of lipid lowering on cardiovascular event rates became an issue of utmost urgency. Although a variety of nonstatin drugs had been tested in clinical trials, they found limited utility in the clinical setting due to lack of mortality reduction or tolerability issues. As multiple prospective randomized statin trials began publishing their results, it became clear that reducing atherogenic lipoprotein burden with these drugs was highly efficacious, safe, and generally well tolerated. Statins have been shown to reduce risk for nonfatal MI, ischemic stroke, need for revascularization, and cardiovascular and all-cause mortality. They have also been shown to stabilize and even regress established atherosclerotic plaque. For the first 2 decades of their use, statin dosing was largely determined by risk-stratified low-density lipoprotein cholesterol (LDL-C) goals. More recently, there has been a transition away from LDL-C goal attainment with a focus more on cardiovascular risk and percent LDL-C reduction. Unfortunately, long-term adherence rates with statin therapy remain low and, even when used, they tend to be underdosed.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Cálculos da Dosagem de Medicamento , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
17.
Methodist Debakey Cardiovasc J ; 15(1): 32-38, 2019 Jan-Mar.
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 , 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
18.
Molecules ; 24(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035343

RESUMO

Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC-MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t1/2, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC0-12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0-12h of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t1/2. However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV.


Assuntos
Interações de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Metabolômica , Silimarina/farmacologia , Sinvastatina/farmacocinética , Animais , Metabolômica/métodos , Estrutura Molecular , Ratos
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(5): 351-359, 2019 May 24.
Artigo em Chinês | MEDLINE | ID: mdl-31142078

RESUMO

Objective: To assess the use of statins and low-density lipoprotein cholesterol (LDL-C) levels at admission in hospitalized patients aged 75 years and older with acute coronary syndrome (ACS) in China. Methods: Data used in this study derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a nationwide registry with 150 tertiary hospitals reporting details of clinical information of ACS patients. This study enrolled patients 75 years and older with ACS in CCC-ACS project from November 2014 to June 2017. Patients were divided into two groups according to the history of atherosclerotic cardiovascular disease (ASCVD). Pre-hospital statin use, LDL-C levels at admission and prescription of statins at discharge were reported. Results: A total of 10 899 patients 75 years and older with ACS were enrolled. The median age was 79 years and 58.7% (6 397 cases) were male. Among patients with history of ASCVD, 33.9% (1 028 cases) of them received statins before hospitalization. Among patients without history of ASCVD, 12.7% (996/7 871) received statins before hospitalization. The mean level of LDL-C was (2.4±0.9) mmol/L and LDL-C was <1.8 mmol/L in 24.7% (747 cases) of patients with history of ASCVD. The mean level of LDL-C was (2.6±0.9) mmol/L and LDL-C was <2.6 mmol/L in 51.7% (4 072 cases) of patients without history of ASCVD. At discharge, 91.2% (9 524/10 488) of patients were prescribed with statins in patients without contraindications for statin. Conclusion: In elderly patients with recurrent ASCVD, there was an inadequate statin use before hospitalization and most patients did not reach the LDL-C target level when they had the recurrent events. In the elderly ACS patients without history of ASCVD, more than half of the patients had an ideal LDL-C level. It seems that ideal LDL-C level for primary prevention of ACS in elderly people needs to be reevaluated with further studies.


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Aterosclerose/tratamento farmacológico , China , LDL-Colesterol , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino
20.
J Manag Care Spec Pharm ; 25(5): 588-592, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31039060

RESUMO

BACKGROUND: Nearly half of statin users discontinue therapy within the first year of treatment. Nonadherence to statin therapy may lead to an increased risk of atherosclerotic cardiovascular disease and, thus, higher costs due to hospitalizations. Value-based care models, such as accountable care organizations (ACO), are measured on adherence rates to statins through proportion of days covered (PDC). However, there is little research describing pharmacy student-based interventions within value-based care models. OBJECTIVES: To (a) identify mean change in PDC for statins following implementation of a pharmacy student adherence outreach program and (b) identify the proportion of patients converted to PDC ≥ 0.80 following the implementation of the outreach program. METHODS: This single-center retrospective quasi-experimental study included patients actively enrolled in a Humana Medicare Advantage Prescription Drug (MA-PD) plan who completed at least 1 adherence outreach telephone call performed by a pharmacy student between January 1, 2017, and December 31, 2017. RESULTS: 99 patients met inclusion criteria. Atorvastatin was the most commonly prescribed statin (43%), followed by simvastatin (38%). Sixty-four percent of patients had a baseline PDC of < 0.80. Mean (SD) PDC was 0.66 (±0.24) before the pharmacy student adherence outreach intervention, and 0.79 (± 0.23)-a 0.13 increase-after the pharmacy student adherence outreach intervention (P < 0.001). Among patients who had PDC < 0.80 at baseline, 35% of patients (n = 35) were converted to PDC ≥ 0.80 (P < 0.001), and 5% of patients with a baseline PDC ≥ 0.80 had a decrease in PDC to < 0.80 following the intervention. CONCLUSIONS: Among patients enrolled in a Humana MA-PD plan within an ACO, mean PDC for statins increased following exposure to a pharmacy student adherence outreach program. One third of patients converted their PDCs to ≥ 0.80 following the intervention. Value-based care programs may consider incorporating pharmacy student services to improve adherence to statins. DISCLOSURES: No outside funding supported this research. The authors have no financial conflicts of interest to disclose. At the time of conducting this research, all authors were employed at Nova Southeastern University. Preliminary results were presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.


Assuntos
Aterosclerose/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Conduta do Tratamento Medicamentoso/organização & administração , Estudantes de Farmácia , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/economia , Feminino , Custos de Cuidados de Saúde , Implementação de Plano de Saúde , Hospitalização/economia , Humanos , Masculino , Programas de Assistência Gerenciada/organização & administração , Medicare Part C/economia , Medicare Part C/estatística & dados numéricos , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Telefone , Estados Unidos
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