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1.
Hum Exp Toxicol ; 38(11): 1283-1295, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31370695

RESUMO

BACKGROUND: Cyclophosphamide (CP) causes premature ovarian failure (POF) due to ovarian toxicity. The toxicity mechanism is attributed to oxidative stress, inflammation, and apoptosis. We assessed whether quercetin and rosuvastatin could promote ovarian protection against CP ovotoxicity. METHODS: A total of 80 female BALB/c mice were randomly assigned; 10 mice into each of eight groups. Group 1 (control), group 2 (EH), group 3 (CP), group 4 (QH), group 5 (QL), group 6 (RH), group 7 (RL), and group 8 (COM). RESULTS: Quercetin and rosuvastatin groups (4:8) showed signs of restored ovarian function in the form of a significant, dose-dependent increase in primordial follicles number, serum anti-Mullerian hormone level, and ovarian tissue glutathione level (p < 0.05) versus group 3, and a significant, dose-dependent decrease in atretic follicles number and ovarian tissue level of malondialdehyde (p < 0.05) versus group 3. Immunohistochemistry analysis demonstrated a lower expression of caspase and nuclear factor-kappa B of groups (4:8) versus group 3, although quercetin and rosuvastatin showed a nonsignificant reduction in tumor volume. CONCLUSIONS: We demonstrated the protective effect of quercetin and rosuvastatin against ovarian toxicity and POF induced by CP without compromising its antitumor effect.


Assuntos
Antineoplásicos , Carcinoma de Ehrlich/tratamento farmacológico , Ciclofosfamida , Insuficiência Ovariana Primária/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Quercetina/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Animais , Hormônio Antimülleriano/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Ehrlich/sangue , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Feminino , Glutationa/metabolismo , Camundongos Endogâmicos BALB C , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/patologia
2.
Adv Skin Wound Care ; 32(9): 1-5, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31403477

RESUMO

OBJECTIVE: To test the hypothesis that platelet-rich plasma (PRP) improves wound healing in rabbits by analyzing morphologic alterations in lesions with the use of PRP alone or combined with rosuvastatin (RSV). METHODS: Eight adult male New Zealand rabbits were used in this study. Researchers created four wounds on the back of each rabbit with an 8-mm punch. The control wound was treated with a 0.9% sodium chloride solution. Experimental wounds were treated with PRP, RSV, or both PRP and RSV. Dressings were changed with a new application of PRP and RSV every 4 days for 16 days. Wounds were biopsied on days 0, 7, 10, 14, and 17 for histopathologic evaluation of the scar tissue. MAIN RESULTS: Histopathology revealed reepithelialization in 100% of wounds treated with PRP alone after 17 days of treatment, compared with 50% of wounds treated with RSV alone and 75% of the wounds treated with PRP and RSV. Further, combining RSV and PRP reduced blood loss. The use of PRP alone induced 100% neovascularization, compared with 50% and 62.5% in wounds treated with PRP and RSV and RSV alone, respectively. All experimental wounds had a higher percentage of collagen fibers on day 17 postlesion when compared with control wounds (78.27% ± 4.69%). There were no significant differences among treatments; however, wounds treated with RSV alone had the lowest amount of collagen fibers (85.98% ± 3.51%). Wounds treated with PRP alone or PRP and RSV had 90.07% ± 6.20% and 90.76% ± 3.51% collagen fibers, respectively. CONCLUSIONS: The results of this study indicate that PRP elicits higher healing activity in the first 7 days postlesion. Treatments with RSV alone or RSV and PRP did enhance other healing phases.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Plasma Rico em Plaquetas , Rosuvastatina Cálcica/uso terapêutico , Úlcera Cutânea/terapia , Ferimentos Penetrantes/terapia , Animais , Modelos Animais de Doenças , Masculino , Coelhos , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Fatores de Tempo , Cicatrização , Ferimentos Penetrantes/etiologia , Ferimentos Penetrantes/patologia
3.
BMC Res Notes ; 12(1): 386, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288848

RESUMO

OBJECTIVE: Although most clinical practice guidelines endorsed statin use in type 2 diabetes (T2D) patients for reducing cardiovascular diseases (CVD), little is known about statin utilization in case of Ethiopia. Hence, this study was aimed to evaluate prescribing pattern of statins for primary prevention of CVD in T2D patients. A retrospective study conducted in T2D patients with the age group of 40-75 years. Prescriptions were audited for details of statin use and dose intensity. Descriptive analysis was performed using SPSS version 22.0. RESULTS: We included a total of 323 study subjects. Of those, 55.7% study subjects were found to be received statin for their primary prevention of CVD. Commonly prescribed type of statins was simvastatin (37.2%), atorvastatin (32.8%) and rosuvastatin (15.6%). Low, moderate and high intensive dose of statins were prescribed in 27.8%, 46.1%, and 26.1%, respectively. Of those subjects received statin, 60.6% had on target cholesterol level. Overall, a significant percentage of subjects did not receive their recommended statin for primary prevention of CVD which is below the guidelines' recommendation. Therefore, adherence to guidelines may help to promote the use of statins for primary prevention of CVD in T2D and advance interventions to improve statin prescribing should be considered.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Padrões de Prática Médica , Adulto , Idoso , Atorvastatina/uso terapêutico , Etiópia , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Rosuvastatina Cálcica/uso terapêutico , Sinvastatina/uso terapêutico
4.
EuroIntervention ; 15(12): e1099-e1106, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31334703

RESUMO

AIMS: We aimed to assess the effect of 10 mg/day of rosuvastatin plus eicosapentaenoic acid (EPA) versus 2.5 mg/day of rosuvastatin on the extent of neoatherosclerosis using optical coherence tomography (OCT). METHODS AND RESULTS: We randomly assigned 50 patients with non-obstructive neoatherosclerotic plaques detected on OCT to receive either rosuvastatin 10 mg/day and EPA 1,800 mg/day (intensive therapy group) or rosuvastatin 2.5 mg (standard therapy group). Follow-up OCT was performed one year later to evaluate serial changes in neoatherosclerosis. The serum low-density lipoprotein cholesterol (LDL-C) level decreased significantly from baseline to 12-month follow-up in the intensive therapy group (89 mg/dL to 70 mg/dL; p<0.001), while no change occurred in the standard therapy group. Lipid index change and percent changes in macrophage grade were significantly lower in the intensive therapy group than in the standard therapy group (-53.6 vs 310.1, p=0.001; -37.0% vs 35.3%, p<0.001; respectively). Percent changes in lipid index and macrophage grade were positively correlated with the changes in serum LDL-C and C-reactive protein levels, and negatively correlated with the change in serum EPA/arachidonic acid and 18-hydroxyeicosapentaenoic acid (EPA bioactive metabolite) level. CONCLUSIONS: Compared with rosuvastatin 2.5 mg/day, rosuvastatin 10 mg/day and EPA 1,800 mg/day significantly stabilised non-obstructive neoatherosclerotic plaques. CLINICAL TRIAL REGISTRATION: UMIN ID: UMIN000012576. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014711.


Assuntos
Aterosclerose/tratamento farmacológico , Ácido Eicosapentaenoico/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/uso terapêutico , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Estudos Prospectivos , Rosuvastatina Cálcica/administração & dosagem , Rosuvastatina Cálcica/efeitos adversos , Tomografia de Coerência Óptica , Resultado do Tratamento
5.
Phytother Res ; 33(7): 1815-1826, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141276

RESUMO

Capsaicinoid nonivamide (PAVA) and rosuvastatin (RSV) have been shown to exert antioxidant and anti-obesity effects in various animal models, but it is unknown whether their combination would be an effective treatment for obesity-related endothelial dysfunction. This study aimed to investigate the mechanism of PAVA in synergy with RSV. Male Sprague-Dawley rats were given a high-fat diet (HFD) or normal diet during a 20-week period. At 16 weeks, rats in each diet group were divided into subgroups. Normal diet rats were divided into Normal diet control, Normal diet with PAVA, and Normal diet with RSV groups. HFD rats were subdivided into HFD control, HFD with PAVA, HFD with RSV, and HFD with PAVA + RSV groups and evaluated for metabolic parameters, blood pressure, aortic function, and histological change of the aorta in rats. Our results showed the combined therapy had a significantly greater effect than the monotherapy in all measured parameters; this was indicated by improvement in insulin sensitivity and aortic function, decreased blood pressure, lower oxidative stress, and prevention of vascular damage. The synergistic effect of the PAVA and RSV can protect HFD-induced obesity-related endothelial dysfunction, suggesting that the combination of PAVA and RSV could be an effective alternative treatment for obesity-related complications in patients with cardiovascular disease.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Capsaicina/análogos & derivados , Obesidade/tratamento farmacológico , Rosuvastatina Cálcica/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Capsaicina/uso terapêutico , Dieta Hiperlipídica , Sinergismo Farmacológico , Quimioterapia Combinada , Resistência à Insulina , Masculino , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
6.
Arterioscler Thromb Vasc Biol ; 39(6): 1182-1190, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31070471

RESUMO

Objective- Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA2-IIA (group IIA secretory phospholipase A2) plays an integral role in regulating vascular inflammation. Although studies investigated sPLA2-IIA in secondary prevention, we prospectively evaluated sPLA2-IIA mass and genetic variants with CVD events in a primary prevention population with chronic inflammation. Approach and Results- The JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) randomized participants with LDL (low-density lipoprotein) <130 mg/dL and hsCRP (high-sensitivity C-reactive protein) ≥2 mg/L to high-intensity rosuvastatin versus placebo. Baseline and 1-year plasma sPLA2-IIA mass was measured (N=11 269 baseline; N=9620 1 year). We also identified genetic variants influencing sPLA2-IIA using genome-wide association and examined them with CVD. Three hundred thirteen incident CVD events occurred during follow-up. Baseline sPLA2-IIA mass (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/mL) was associated with increased risk of CVD: risk factor-adjusted hazard ratio (95% CI; P) per SD increment: 1.22 (1.08-1.38; P=0.002). This remained significant (1.18; 1.04-1.35; P=0.01) after incrementally adjusting for hsCRP. Similar estimates were observed in rosuvastatin and placebo groups ( P treatment interaction>0.05). The rs11573156C variant in PLA2G2A (encoding sPLA2-IIA) had the strongest effect on sPLA2-II: median (25th-75th percentile, ng/mL) for CC and GG genotypes: 2.79 (1.97-4.01) and 7.38 (5.38-10.19), respectively; and had nonsignificant trend for higher CVD risk (hazard ratio, 1.11; 95% CI, 0.89-1.38; P=0.34). Conclusions- In the JUPITER population recruited on chronic inflammation, sPLA2-IIA mass was associated with CVD risk relating to vascular inflammation not fully reflected by hsCRP. Additional studies, including larger functional genetic and clinical studies, are needed to determine whether sPLA2-IIA may be a potential pharmacological target for primary prevention of CVD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.


Assuntos
Doenças Cardiovasculares/enzimologia , Dislipidemias/enzimologia , Fosfolipases A2 do Grupo II/sangue , Inflamação/enzimologia , Idoso , Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Dislipidemias/genética , Feminino , Predisposição Genética para Doença , Fosfolipases A2 do Grupo II/genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Inflamação/tratamento farmacológico , Inflamação/epidemiologia , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevenção Primária , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Rosuvastatina Cálcica/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
7.
Med Arch ; 73(1): 19-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31097854

RESUMO

Introduction: Postoperative Atrial Fibrillation (POAF) is associated with a higher rate of postoperative complications and mortality, as well as with longer hospitalization and increased treatment costs. We have designed and performed a randomized, trial of pharmacological prophylaxis in which the event of interest is POAF. Aim: The aim of this study is to reduce the risk of postoperative, complications associated with this arrhythmia. Methods: We included 240 stable patients with a coronary heart disease, who were referred to elective surgical revascularization of the myocardium. The patients were assigned into three groups of 80 patients each: group A (BB, beta blocker, comparator), group B (BB+ Amiodarone) and group C (BB + Rosuvastatin). The goal was to establish whether intervention by combination therapy was more useful than a comparator. Results: An event of interest (POAF) has occurred in 66 of the total 240 patients. Number of new POAF cases is the lowest in Group B, 14 (17.5%) compared to 25 (31.25%) new cases in the comparator group, and 27 new cases (33.75%) in group C. Absolute risk reduction was 13.75%, ≈14% less POAF in group B compared to comparator. Relative risk reduction was 56% (RR 0.56, p = 0.04). Number Needed to Treat was 7.27. In group C, 33.75% of patients developed POAF. Absolute risk was insignificantly higher in group C (2.5%, NS) compared to the comparator .The number needed to harm was high, 40. Conclusion: The results of our research show that prophylaxis of POAF with combined therapy BB + Amiodarone was the most efficient one.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/prevenção & controle , Revascularização Miocárdica/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Rosuvastatina Cálcica/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/etiologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Complicações Pós-Operatórias/etiologia , Rosuvastatina Cálcica/administração & dosagem
8.
Int J Oncol ; 54(6): 2149-2156, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942448

RESUMO

Mitotane (also termed o,p'­DDD) is the most effective therapy for advanced adrenocortical carcinoma (ACC). Mitotane­induced dyslipidemia is treated with statins. Mitotane and statins are known to exert anti­proliferative effects in vitro; however, the effects of statins have never been directly evaluated in patients with ACC and ACC cells, at least to the best of our knowledge. Thus, in this study, we aimed to examine the effects of the rosuvastatin on ACC cells. It has been shown that the combined use of mitotane and statins significantly increases the tumor control rate in patients with ACC; however, it would be of interest to elucidate the molecular mechanisms involved in this potentiation. In this study, we examined the effects of mitotane, rosuvastatin and their combination in NCI­H295R human ACC cells using proliferation assays, gene expression analyses and free intracellular cholesterol measurements. The results revealed that mitotane dose­dependently reduced cell viability, induced apoptosis and increased intracellular free cholesterol levels, considered as one of the key features of mitotane action, while rosuvastatin alone reduced cell viability and increased apoptosis at high concentrations. We also demonstrated that rosuvastatin potentiated the effects of mitotane by reducing cell viability, inducing apoptosis, increasing intracellular free cholesterol levels, and by decreasing the expression of 3­hydroxy­3­methylglutaryl­CoA reductase (HMGCR) and ATP binding cassette subfamily a member 1 (ABCA1), genes involved in cholesterol metabolism, and inhibiting steroidogenesis. Collectively, potentiating the effects of mitotane with the use of rosuvastatin may provide novel therapeutic strategies for ACC, given that the combination of these drugs, pending clinical validation, may lead to the better management of ACC.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Mitotano/farmacologia , Rosuvastatina Cálcica/farmacologia , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Mitotano/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico
9.
Colloids Surf B Biointerfaces ; 177: 541-549, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825846

RESUMO

The present work entails development of novel phospholipid-based self-nanoemulsifying systems (SNES) of rosuvastatin calcium for improving the oral biopharmaceutical performance via intestinal lymphatic pathways. The phospholipid complex-loaded SNES exhibited emulsification time of 142 s, particle size of 182.5 nm, polydispersity index of 0.35, zeta potential of -22.5 mV and complete in vitro drug release within 3 h. Cell line study on Caco-2 indicated absence of cytotoxicity and excellent cellular uptake of PL-SNES vis-à-vis plain SNES. Permeability study revealed >85% enhancement in the permeation, while intestinal perfusion study showed 2.9 and 3.5-fold increase in the permeation and absorption of the drug from the optimized PL-SNES over the pure drug suspension. Nearly 2.2 and 7.2-folds improvement in AUC0-t and Cmax, and 0.33-fold reduction in the Tmax of drug was observed for PL-SNES vis-à-vis the pure drug suspension during pharmacokinetic study. Moreover, PL-SNES also showed superior antihyperlipidemic activity over the pure drug suspension during pharmacodynamic study. Overall, the developed nanoformulation yielded significant improvement in the oral deliverability of the explored drug candidate.


Assuntos
Quilomícrons/química , Hiperlipidemias/tratamento farmacológico , Nanopartículas/química , Rosuvastatina Cálcica/administração & dosagem , Rosuvastatina Cálcica/uso terapêutico , Animais , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Coloides/química , Portadores de Fármacos/química , Humanos , Hiperlipidemias/patologia , Masculino , Ratos , Ratos Wistar , Rosuvastatina Cálcica/química , Rosuvastatina Cálcica/farmacologia
10.
Neurology ; 92(13): e1435-e1446, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30814321

RESUMO

OBJECTIVE: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. METHODS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. RESULTS: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. CONCLUSIONS: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. CLINICALTRIALSGOV IDENTIFIER: NCT00468923. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Disfunção Cognitiva/epidemiologia , Hidroclorotiazida/uso terapêutico , Hipolipemiantes/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Cognição , Combinação de Medicamentos , Feminino , Humanos , Masculino
11.
Georgian Med News ; (286): 67-72, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30829592

RESUMO

The aim of the study was to increase the efficacy of treatment of patients with HFHC and NASH by developing a personified approach to the therapy with rosuvastatin 20 mg/day and combined hepatoprotector at the inpatient and outpatient stages of treatment. 124 patients with clinical HFHC were examined. The object of the study was 55 patients (age 55.45±5.5 years) with a clinical diagnosis of HFHC, NASH. All patients underwent a detailed physical examination, laboratory-instrumental (general clinical, biochemical (hepatic transaminases, lipidogram, ultrasonography of the abdominal organs), molecular genetic examination (polymorphism of the SLCO1B1 gene). Two groups of study were formed, in the first group patients received rosuvastatin 20 mg/day, in the second group - rozuvastatin 20 mg/day and combined hepatoprotector 2 capsules 3 times a day for 90 days. The patients treated with rosuvastatin 20 mg/day and hepatoprotector were revealed a reliable decrease in the level of TC by 46%, which was 5.1±0.59 mmol/l (p<0.005), the level of LDL significantly decreased by 68.5% - 2.23±0.58 mmol/l (p<0.005), the level of HDL increased by 73% and amounted to 2.56±0.29 mmol/l (p<0.005). On the 90th day of therapy, the activity of hepatic transaminases reached reference values: ALT 32.16±7.83 units/l, AST - 30.11±6.32 units/l (p<0.005). Based on the complex examination and determination of polymorphism of SLCO1B1, a personified dose of statin was selected.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Hepatopatia Gordurosa não Alcoólica , Rosuvastatina Cálcica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Polimorfismo Genético , Rosuvastatina Cálcica/uso terapêutico , Resultado do Tratamento
12.
Am J Cardiol ; 123(10): 1565-1571, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851941

RESUMO

Statins are widely used to lower cholesterol and to reduce cardiovascular events. Whether all statins have similar effects on plaque stabilization is unknown. We aimed to investigate coronary plaque response to treatment with different statins that result in similar lipid reduction using serial multimodality intracoronary imaging. Patients with de novo coronary artery disease requiring intervention were randomized to rosuvastatin 10mg (R10) or atorvastatin 20mg (A20) daily. Optical coherence tomography and intravascular ultrasound were performed at baseline, 6 months, and 12 months. Untreated nonculprit plaques were analyzed by optical coherence tomography for thin-cap fibroatheroma, minimum fibrous cap thickness, lipid arc, and lipid length. Total and percent atheroma volume, respectively were analyzed by intravascular ultrasound. Forty-three patients completed the protocol (R10: 24 patients, 31 plaques; A20: 19 patients, 30 plaques). The decrease in serum lipids was similar. From baseline to 6 months to 12 months, minimum fibrous cap thickness increased in the R10 group (61.4 ± 15.9 µm to 120.9 ± 57.9 µm to 171.5 ± 67.8 µm, p <0.001) and the A20 group (60.8 ± 18.1 µm to 99.2 ± 47.7 µm to 127.0± 66.8 µm, p <0.001). Prevalence of thin-cap fibroatheroma significantly decreased in the R10 and A20 groups (-48% and -53%, respectively, p <0.001 for intragroup comparisons). Only the R10 group had a decrease in macrophage density (-23%, p = 0.04) and microvessels (-12%, p = 0.002). Total atheroma volume decreased in the R10 group (109.2 ± 62.1 mm3 to 101.8 ± 61.1 mm3 to 102.5 ± 62.2 mm3, p = 0.047) but not in the A20 group (83.3 ± 48.5mm3 to 77.6 ± 43.0 mm3 to 77.9 ± 48.6 mm3, p = 0.07). In conclusion, although both statins demonstrated similar reductions in lipid profiles, the rosuvastatin group showed more rapid and robust plaque stabilization, and regression of plaque volume compared to the atorvastatin group.


Assuntos
Atorvastatina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Rosuvastatina Cálcica/uso terapêutico , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Estudos Prospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
13.
Int J Clin Pharm ; 41(2): 460-469, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30864086

RESUMO

Background While there is clear evidence for the benefit of statins in the secondary prevention of cardiovascular and cerebrovascular events, there is a lack of research on the effects of statin regimens in older patients aged 75 years and over. Objectives To compare the effectiveness of statin regimens in the secondary prevention of ischemic cardiovascular and cerebrovascular events among patients aged 75 years and over. Setting Claims data from the South Korean National Health Insurance Database from 2006 to 2014. Methods This retrospective cohort study included patients aged 75-100 years with a prior history of cardiovascular or cerebrovascular disease who began statin therapy in 2009-2011. Propensity score matching and the Cox proportional hazards regression model were used to compare the effectiveness of the statin regimens in secondary prevention. Main outcome measure The hazard ratios for ischemic cardiovascular and cerebrovascular events and all-cause mortality. Results Neither high nor low-intensity statin therapy significantly differed from moderate-intensity statin therapy in preventing ischemic cardiovascular and cerebrovascular events or all-cause mortality. Of the moderate-intensity statin therapies, the use of 10 mg rosuvastatin was more strongly associated with a reduced risk of ischemic cardiovascular and cerebrovascular events than was 10 mg atorvastatin [HR 0.79 (95% CI 0.64-0.98), p = 0.029]. Subgroup analysis revealed that the protective effects of 10 mg rosuvastatin against ischemic cardiovascular and cerebrovascular events were more obvious for patients who were 75-79 years old, those who were statin-adherent, those who did not have diabetes mellitus at baseline, and those who were non-adherent to aspirin or antiplatelet drugs during the selection and follow-up periods. Conclusion The results of this study support the preferential prescription of moderate-intensity rosuvastatin over moderate-intensity atorvastatin for the secondary prevention of ischemic cardiovascular and cerebrovascular events in older patients aged ≥ 75 years.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Secundária/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Atorvastatina/uso terapêutico , Feminino , Humanos , Benefícios do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Masculino , Fatores de Proteção , Estudos Retrospectivos , Rosuvastatina Cálcica/uso terapêutico
14.
Med Decis Making ; 39(3): 264-277, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30873906

RESUMO

BACKGROUND: Patients and clinicians are often required to make tradeoffs between the relative benefits and harms of multiple treatment options. Combining network meta-analysis results with user preferences can be useful when choosing among several treatment alternatives. OBJECTIVE: Using cholesterol-lowering statin drugs as a case study, we aimed to determine whether an interactive web-based platform that combines network meta-analysis findings with patient preferences had an effect on the decision-making process in a general population sample. METHOD: This was a pilot parallel randomized controlled trial. We used Amazon's Mechanical Turk to recruit adults residing in the United States. A total of 349 participants were randomly allocated to view either the interactive tool (intervention) or a series of bar charts (control). The primary endpoint was decisional conflict, and secondary endpoints included decision self-efficacy, preparation for decision making, and the overall ranking of statins. RESULTS: A total of 258 participants completed the trial and were included in the analysis. On the primary outcome, participants randomized to the interactive tool had significantly lower levels of decisional conflict than those in the control group (difference, -8.53; 95% confidence interval [CI], -12.96 to -4.11 on a 100-point scale; P = 0.001). They also appeared to have higher levels of preparation for decision making (difference, 4.19; 95% CI, -0.24 to 8.63 on a 100-point scale; P = 0.031). No difference was found for decision self-efficacy, although groups were statistically significantly different in how they ranked different statins. CONCLUSION: The findings of our proof-of-concept evaluation suggest that an interactive web-based tool combining published clinical evidence with individual preferences can reduce decisional conflict and better prepare individuals for decision making.


Assuntos
Técnicas de Apoio para a Decisão , Inibidores de Hidroximetilglutaril-CoA Redutases/normas , Preferência do Paciente/psicologia , Medicina de Precisão/métodos , Adulto , Atorvastatina/normas , Atorvastatina/uso terapêutico , Comportamento de Escolha , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lovastatina/normas , Lovastatina/uso terapêutico , Masculino , Preferência do Paciente/estatística & dados numéricos , Projetos Piloto , Pravastatina/normas , Pravastatina/uso terapêutico , Medicina de Precisão/normas , Medicina de Precisão/estatística & dados numéricos , Psicometria/instrumentação , Psicometria/métodos , Rosuvastatina Cálcica/normas , Rosuvastatina Cálcica/uso terapêutico , Autoeficácia , Sinvastatina/normas , Sinvastatina/uso terapêutico
15.
Prensa méd. argent ; 105(1): 34-40, mar 2019. tab, graf
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1026338

RESUMO

Being the main treatment for cholelithiasis, laparoscopic cholecystectomy does not always solve the problem. It often entails postcholecystectomy syndrome (PCS). Oral medication to dissolve gallstones with bile acids is alternative therapy for some patients. However, lack of efficacy and limited medical indications make it necessary to apply combination treatment tactics. This study was conducted to investigate the dissolution of gallstones during the combined effects of ursodeoxycholic acid (UDCA) and rosuvastatin as well as to assess the results of eradication therapy in the presence of H. pylory as a measure to prevent cholelithiasis in the course of treatment.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ácido Ursodesoxicólico/uso terapêutico , Colelitíase/prevenção & controle , Colelitíase/tratamento farmacológico , Administração Oral , Helicobacter pylori , Quimioterapia Combinada/tendências , Erradicação de Doenças , Rosuvastatina Cálcica/uso terapêutico
16.
Am J Cardiovasc Drugs ; 19(4): 415-420, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30793259

RESUMO

INTRODUCTION: Atherosclerosis erodes large elastic arteries and damages peripheral small vessels. Evaluating retinal vessel caliber enables exploration of the effect of improving microcirculation with statins. OBJECTIVE: We investigated whether rosuvastatin therapy improves retinal vasculature in hypercholesterolemic patients with a low-to-moderate risk of coronary artery disease (CAD). METHODS: This was a prospective, open-label, randomized study in which 127 patients were enrolled and randomized (ratio 1:1) into rosuvastatin and control groups. RESULTS: Rosuvastatin increased retinal arteriolar calibers by 3.560 µm at 12 months, decreased retinal venular calibers by 3.110 µm at 6 months and by 5.860 µm at 12 months, and increased the artery-vein ratio (AVR) by 2.68% at 6 months and by 5.90% at 12 months. Meanwhile, in the control group, retinal arteriolar calibers decreased by 1.110 µm at 12 months, retinal venular calibers increased by 1.020 µm at 6 months and by 1.04 µm at 12 months, and AVR decreased by 1.12% at 6 months and by 1.73% at 12 months. All the above parameters were statistically significant between groups, but there was no significant change in retinal arteriolar calibers at 6 months. The increased AVR correlated significantly with decreased C-reactive protein (CRP) at 6 months and decreased low-density lipoprotein and CRP at 12 months. DISCUSSION: For patients with a low-to-moderate risk of CAD, we found a significant effect of rosuvastatin on retinal microvasculature, including AVR increase, venular constriction, and arteriolar dilation after 6-12 months of treatment. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier number ChiCTR-IOR-15006664.


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Vasos Retinianos/efeitos dos fármacos , Rosuvastatina Cálcica/uso terapêutico , Arteríolas/efeitos dos fármacos , Grupo com Ancestrais do Continente Asiático , Aterosclerose/metabolismo , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Vênulas/efeitos dos fármacos
17.
BMJ Case Rep ; 12(2)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30798276

RESUMO

This 37-year-old man presented with left sided facial warmth and numbness associated with new sudden-onset right hemiparesis. The patient first developed sudden numbness of his left lip and warmth in left ear which travelled to the rest of left face. His past medical history was significant for hypertension, Hodgkin lymphoma treated with radiation therapy at the age of 10, and sleeve gastrectomy for obesity 1 year ago complicated by bilateral ischaemic cerebral infarctions with residual left hemiparesis. No acute infarcts were found on MRI. Transesophageal echocardiography revealed a complex atheroma near the sinotubular junction in ascending aorta.


Assuntos
Valva Aórtica/fisiologia , Doenças das Valvas Cardíacas/diagnóstico , Paresia/etiologia , Acidente Vascular Cerebral/diagnóstico , Adulto , Anticolesterolemiantes/uso terapêutico , Valva Aórtica/diagnóstico por imagem , Aspirina/uso terapêutico , Ecocardiografia Transesofagiana , Inibidores do Fator Xa/uso terapêutico , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Paresia/fisiopatologia , Rivaroxabana/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
18.
Am Heart J ; 210: 18-28, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716508

RESUMO

The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations. METHODS: We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes. RESULTS: In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile. CONCLUSIONS: All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Atorvastatina/efeitos adversos , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Método Duplo-Cego , Fluvastatina/efeitos adversos , Fluvastatina/uso terapêutico , Cefaleia/induzido quimicamente , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Nefropatias/induzido quimicamente , Lovastatina/efeitos adversos , Lovastatina/uso terapêutico , Pessoa de Meia-Idade , Doenças Musculares/induzido quimicamente , Náusea/induzido quimicamente , Neoplasias/induzido quimicamente , Placebos/uso terapêutico , Pravastatina/efeitos adversos , Pravastatina/uso terapêutico , Medição de Risco , Rosuvastatina Cálcica/efeitos adversos , Rosuvastatina Cálcica/uso terapêutico , Sinvastatina/efeitos adversos , Sinvastatina/uso terapêutico , Suspensão de Tratamento
19.
J Cardiovasc Pharmacol Ther ; 24(3): 233-241, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30599756

RESUMO

OBJECTIVE: Chemotherapy-induced cardiotoxicity is a major and leading cause of death in breast cancer survivors. It can present decades after chemotherapy and can manifest in different ways; some chemotherapeutic agents have a powerful dose-dependent relationship with cardiotoxicity. The aim of this study was to investigate the effect of rosuvastatin on preventing chemotherapy-induced cardiotoxicity in patients with breast cancer. METHODS: Our study was a randomized, single-blind, placebo-controlled trial that involved 89 women with newly diagnosed breast cancer who were scheduled to receive chemotherapy. Patients were randomly assigned to receive rosuvastatin or a placebo in a 1:1 ratio for 6 months. Echocardiography, using 2-dimensional (2D) Doppler, tissue Doppler, and speckle-tracking methods, was used to determine the absolute changes in the left ventricular systolic ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial (LA) diameter, transmitral Doppler early diastolic velocity (E wave), tissue Doppler early diastolic (e') and peak systolic (s') mitral annular velocities, E/e' ratio, and global longitudinal systolic strain. RESULTS: The LVEF was significantly reduced in the placebo group at the end of the study when compared with the baseline value. However, there was no significant difference in the LVEF in the intervention group (intergroup P = .012). Furthermore, compared with the intervention group at the end of the study, there was a significant increase in the 4- and 2-chamber LVESV, LA diameter, and E/e' ratio in the placebo group (intergroup P = .019, P = .024, P < .001, and P = .021, respectively) and a significant decrease in the e' and s' velocities in the placebo group (intergroup P < .001 and P < .006, respectively). CONCLUSIONS: The present study showed that the prophylactic use of rosuvastatin may prevent the development of chemotherapy-induced cardiotoxicity.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Cardiotoxicidade , Ecocardiografia Doppler , Feminino , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Estudos Prospectivos , Substâncias Protetoras/efeitos adversos , Rosuvastatina Cálcica/efeitos adversos , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
20.
Res Social Adm Pharm ; 15(3): 252-259, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29753643

RESUMO

BACKGROUND: Individuals who suffer from major cardiovascular events every year have one or more risk factors. Cardiovascular disease (CVD) risk assessment is an important strategy for the early identification of modifiable risk factors and their management. There is substantial evidence that shifting the focus from treatment to primary prevention reduces the burden of CVD. OBJECTIVES: To evaluate the preparedness of community pharmacists in Qatar for the provision of CVD risk assessment and management services; and to explore the pharmacists' views on the provision of these services. METHODS: A cross-sectional study using simulated-client methodology. Using standardized scenarios, community pharmacists were approached for consultation on two medicines (Aspirin® and Crestor®) used for managing specific CVD risk factors. Pharmacists' competency to assess CVD risk was the primary outcome evaluated. Scores for each outcome were obtained based on the number of predefined statements addressed during the consultation. RESULTS: The mean cumulative score for all the competency outcomes assessed was 11.7 (SD 3.7) out of a possible score of 31. There were no differences for the majority of the competencies tested between the two scenarios used. Significantly more pharmacists exposed to the Aspirin® scenario than to the Crestor® scenario addressed hypertension as one of the risk factors needed to assess CVD risk (22% versus 11%, p = 0.03); whereas significantly more pharmacists in the Crestor® scenario compared to the Aspirin® scenario, addressed dyslipidemia as one of the risk factors needed to assess CVD risk (30% versus 7%, p = 0.02). Significantly more pharmacists exposed to the Aspirin® scenario provided explanation about CVD risk than those exposed to the Crestor® scenario 36% versus 8%, p < 0.01). CONCLUSION: The results suggest that many community pharmacists in Qatar are not displaying competencies that are necessary for the provision of CVD prevention services.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Competência Clínica , Serviços Comunitários de Farmácia , Farmacêuticos , Medição de Risco , Adulto , Aspirina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Paciente , Prevenção Primária , Papel Profissional , Catar , Rosuvastatina Cálcica/uso terapêutico
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