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1.
Parasit Vectors ; 17(1): 51, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308372

RESUMO

BACKGROUND: Babesia canis is a clinically relevant vector-borne pathogen in dogs, and its presence is expanding. The efficacy of Simparica Trio® (Zoetis) in the prevention of B. canis transmission was evaluated at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight. METHODS: Twenty-four (24) dogs were randomly allocated to either a placebo-treated group or one of two treatment groups with Simparica Trio. Dogs were infested with B. canis-infected Dermacentor reticulatus ticks 21 or 28 days after treatment administration. Blood samples for antibody and DNA detection were collected from each dog prior to tick infestation until 28 days after infestation. A dog was defined as being B. canis positive if it tested positive by both an indirect immunofluorescence assay (IFA) and PCR at any time during the study. RESULTS: No treatment-related adverse reactions were recorded during the study. All placebo-treated animals displayed clinical signs due to babesiosis and tested positive on both IFA and PCR. None of the Simparica Trio-treated animals displayed any clinical symptoms or tested positive, resulting in a 100% efficacy in the prevention of canine babesiosis (P < 0.0001). CONCLUSIONS: A single treatment with Simparica Trio at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight prevents the transmission of B. canis by infected D. reticulatus to dogs for at least 28 days.


Assuntos
Acaricidas , Babesia , Babesiose , Doenças do Cão , Animais , Cães , Acaricidas/uso terapêutico , Administração Oral , Azetidinas , Babesia/genética , Babesiose/prevenção & controle , Dermacentor , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Macrolídeos , Pirantel/uso terapêutico , Compostos de Espiro , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária
2.
Nat Commun ; 15(1): 1430, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365756

RESUMO

Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).


Assuntos
Anticorpos Monoclonais Humanizados , Azetidinas , Melanoma , Piperidinas , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/etiologia , Vemurafenib/uso terapêutico , Terapia Neoadjuvante , Proteínas Proto-Oncogênicas B-raf/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Mutação
4.
J Immunother Cancer ; 12(2)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316517

RESUMO

BACKGROUND: Pancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer. METHODS: In the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one or two prior regimens) received nivolumab 3 mg/kg every 2 weeks, ipilimumab 1 mg/kg every 6 weeks, and cobimetinib 60 mg orally once daily for 21 days on and 7 days off (triplet arm). The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints were investigator-assessed progression-free survival (PFS), PFS rate, overall survival (OS), OS rate, safety, and tolerability. Additionally, ORR, PFS, and duration of response were assessed by blinded independent central review (BICR) in the triplet arm. RESULTS: 18 patients received nivolumab monotherapy, 21 received nivolumab plus ipilimumab, and 30 received nivolumab plus ipilimumab plus cobimetinib. In the triplet arm, partial responses were observed in two patients per investigator (ORR 6.7% (95% CI 0.8% to 22.1%)) and in three patients per BICR (ORR 10% (95% CI 2.1% to 26.5%)); no responses were observed in the other arms. Median (95% CI) PFS per investigator was 1.4 (1.3 to 2.0), 1.4 (1.2 to 2.7), and 3.0 (1.5 to 4.1) months for the monotherapy, nivolumab plus ipilimumab, and triplet arms, respectively. Median (95% CI) OS was 5.1 (2.0 to 9.0) months, 4.0 (1.9 to 5.6) months, and 6.2 (3.9 to 11.4) months, respectively. Most treatment-related adverse events were grade 2 or less. CONCLUSIONS: Nivolumab with or without ipilimumab did not elicit objective responses in previously treated patients with advanced pancreatic adenocarcinoma, although three confirmed partial responses and manageable safety were observed with cobimetinib-containing triplet therapy. The small sample size and differences in baseline disease-specific characteristics between arms limit interpretation of these results.


Assuntos
Adenocarcinoma , Azetidinas , Neoplasias Pancreáticas , Piperidinas , Humanos , Nivolumabe/uso terapêutico , Ipilimumab/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico
5.
Health Technol Assess ; 28(4): 1-113, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38343072

RESUMO

Background: Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus). Objectives: To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib). Data sources: Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review. Methods: A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources. Results: Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost. Conclusions: The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations. Future work and limitations: The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective. Study registration: This study is registered as PROSPERO CRD42021266219. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.


Atopic dermatitis is one of the most common skin conditions in children but can also develop in adulthood. People with atopic dermatitis have dry, red (inflamed) skin that is also extremely itchy (pruritus). There is no cure for atopic dermatitis. Therapy starts with topical treatments that are applied to the skin, such as emollients. Severe forms of atopic dermatitis are often treated with systemic treatments, which are drugs that are provided as tablets or an injection. Ciclosporin A is often the first systemic therapy given. If atopic dermatitis does not get better with ciclosporin A, options available in the National Health Service are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for atopic dermatitis but have not been assessed for use in the National Health Service are abrocitinib, tralokinumab and upadacitinib. The aim of this project is to review the medical benefits, risks and value for money for the National Health Service of abrocitinib, tralokinumab and upadacitinib for the treatment of moderate-to-severe atopic dermatitis in a multiple technology appraisal. Our review found that: For children aged between 12 and 18 years, abrocitinib and a low dose of upadacitinib (15 mg) are good value for money for the National Health Service. For adults who need a first systemic treatment, upadacitinib is unlikely to be good value for money for the National Health Service. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, upadacitinib 15 mg and tralokinumab could be good value for money for the National Health Service if they are used on their own. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, but need to take it with steroid cream, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab could all be good value for money for the National Health Service.


Assuntos
Anticorpos Monoclonais , Azetidinas , Dermatite Atópica , Eczema , Compostos Heterocíclicos com 3 Anéis , Purinas , Pirazóis , Pirimidinas , Sulfonamidas , Criança , Adulto , Adolescente , Humanos , Pré-Escolar , Dermatite Atópica/tratamento farmacológico , Ciclosporina/uso terapêutico , Medicina Estatal , Resultado do Tratamento , Análise Custo-Benefício
6.
J Med Chem ; 67(4): 2529-2548, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38331432

RESUMO

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99 values <10 µM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.


Assuntos
Azetidinas , Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Azetidinas/farmacologia , Azetidinas/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Testes de Sensibilidade Microbiana
9.
Parasit Vectors ; 17(1): 32, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267960

RESUMO

BACKGROUND: In January 2021, a female 1-year-old Kunekune was presented at the University Clinic for Swine with severe reduction of the field of vision resulting in prolonged reaction time when targeting barriers, due to moderate to severe thickening of the skin around both orbits also affecting the eyelids. METHODS: Clinical examination revealed skin hyperplasia, nodular enlargement of the skin pores of the axillar and inguinal region. Ophthalmologists decided to remove parts of the thickened periocular skin, followed by histopathological examination. RESULTS: Once large amounts of demodectic mites were detected by histopathology, demodicosis could be diagnosed and treatment of the pig was started using sarolaner. Morphological and molecular analyses were performed. Histopathological and parasitological exams led to the aetiological diagnosis of demodicosis in the affected Kunekune pig. Severe skin lesions were revealed to be the consequence of an infestation with Demodex sp. Morphological analyses confirmed the involvement of D. phylloides. Molecular characterization indicated a Demodex species closely related to mites documented in wild boar - most probably D. phylloides for which no explicit sequences are available in GenBank yet. Treatment with sarolaner (2.6 mg/kg) resulted in a substantial regression of skin lesions, already detectable 1 month after first treatment. CONCLUSIONS: Demodicosis is a very rare disease in pigs that is most probably related to an impaired immune response to the mites. Demodectic mange should be included in the list of differential diagnoses in cases of periocular alterations of the skin of pigs.


Assuntos
Azetidinas , Pele , Compostos de Espiro , Suínos , Animais , Feminino , Instituições de Assistência Ambulatorial , Diagnóstico Diferencial
10.
Intern Med ; 63(3): 461-464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38296523

RESUMO

A 48-year-old woman visited our hospital because of bilateral lacrimal gland enlargement. Her serum immunoglobulin G4 (IgG4) level was high, and positron emission tomography-computed tomography showed significant positive findings in the bilateral lacrimal gland. A biopsy revealed a considerable increase in IgG4/CD138, leading to a diagnosis of IgG4-related dacryoadenitis. The disease did not respond to steroid therapy, so treatment was started with baricitinib because of exacerbation of the original atopic dermatitis and dacryoadenitis after the second dose of the coronavirus disease 2019 (COVID-19) vaccine. Baricitinib was effective for resolving both dermatitis and dacryoadenitis, and steroids were able to be discontinued. The IgG4 level also improved.


Assuntos
Azetidinas , Dacriocistite , Aparelho Lacrimal , Purinas , Pirazóis , Sulfonamidas , Feminino , Humanos , Pessoa de Meia-Idade , Dacriocistite/etiologia , Aparelho Lacrimal/patologia , Biópsia/efeitos adversos , Imunoglobulina G
11.
Int Immunopharmacol ; 127: 111435, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38150881

RESUMO

BACKGROUNDS AND AIMS: Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over the last few years, with the advancement of novel treatment approaches. The current systematic review aims to evaluate the safety and efficacy of Janus kinase (JAK) inhibitors and spleen tyrosine kinase (Syk) inhibitors in treating HS. METHOD: A thorough systematic search was performed on PubMed/Medline, Web of Science, and Ovid Embase databases up to September 23th, 2023. Clinical studies published in English were included. RESULTS: Our search yielded ten articles with a total of 165 patients treated with four types of JAK inhibitors (upadacitinib, povorcitinib, tofacitinib, and baricitinib) and one Syk inhibitor (fostamatinib). Upadacitinib, povorcitinib, and tofacitinib improved clinical outcomes, with a significant reduction in hidradenitis suppurativa clinical response (HiSCR) and abscess and inflammatory nodule count (AN count) during the treatment period. Also, these drugs are well tolerated in most HS patients with minimal adverse events (AEs). Moreover, baricitinib depicted an amelioration in signs and symptoms of HS in one case report. Also, fostamatinib exhibited favorable tolerability throughout a 12-week in moderate-to-severe HS patients. The remarkable clinical improvement, as assessed through HiSCR and hidradenitis suppurativa severity (IHS4), corresponded closely with serological indicators of inflammation following fostamatinib administration was achieved. CONCLUSION: JAK and Syk inhibitors are potentially efficacious in managing moderate-to-severe HS since the proinflammatory cytokines are mediated by JAK and Syk signaling pathways. However, further research with a more rigorous examination is mandatory to evaluate such medication's long-term safety and efficacy.


Assuntos
Aminopiridinas , Azetidinas , Hidradenite Supurativa , Inibidores de Janus Quinases , Morfolinas , Purinas , Pirazóis , Pirimidinas , Sulfonamidas , Humanos , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/diagnóstico , Adalimumab/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Baço , Quinase Syk , Resultado do Tratamento , Índice de Gravidade de Doença
14.
Medicine (Baltimore) ; 102(48): e36313, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050265

RESUMO

BACKGROUND: This study aimed to investigate the efficacy and safety of baricitinib in patients with severe coronavirus disease 2019 (COVID-19). METHODS: Databases were searched for studies that compared the clinical efficacy and adverse effects of baricitinib with standard therapy for the treatment of severe COVID-19 and clearly reported relevant outcomes published until December 31, 2022. The corresponding data were extracted from these studies. A fixed-effects model was used to calculate the pooled estimates. The study protocol can be accessed at PROSPERO (CRD42023394173). RESULTS: The baricitinib group had a significantly lower mortality rate and proportion of patients who received mechanical ventilation than the control group (OR = 0.61, 0.57; P = .008, 0.02; 95% CI 0.42-0.88; 0.35-0.92; I2 = 71% and 86%, respectively). The length of hospital stay and rates of severe adverse events were not significantly different between the 2 groups. CONCLUSION: Baricitinib reduces mortality and mechanical ventilation requirements in patients with severe COVID-19. Therefore, we developed a comprehensive understanding of the role of baricitinib in patients with severe COVID-19.


Assuntos
Azetidinas , COVID-19 , Humanos , Tratamento Farmacológico da COVID-19 , Azetidinas/uso terapêutico , Grupos Controle
16.
Eur J Med Res ; 28(1): 536, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990249

RESUMO

OBJECTIVES: Several clinical trials have evaluated the efficacy and safety of baricitinib in COVID-19 patients. Recently, there have been reports on critical patients, which are different from previous research results. The meta-analysis was performed to investigate the effects of baricitinib in COVID-19, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. METHODS: Studies were searched in PubMed, Embase, and Cochrane Library databases on January 31, 2023. We performed a meta-analysis to estimate the efficacy and safety of baricitinib for the treatment of hospitalized adults with COVID-19. This study is registered with INPLASY, number 202310086. RESULTS: A total of 3010 patients were included in our analyses. All included studies were randomized controlled trials or prospective study. There was no difference in 14-day mortality between the two groups [OR 0.23 (95% CI 0.03-1.84), I2 = 72%, P = 0.17]. In subgroup analyses we found that baricitinib did not seem to improve significantly in 24-day mortality critically ill patients [OR 0.60 (95% CI 0.35-1.02), I2 = 0%, P = 0.06]. Fortunately, baricitinib have led to faster recovery and shorter hospital stays for COVID-19 patients. There were no difference in infections and infestations, major adverse cardiovascular events, deep vein thrombosis and pulmonary embolism. CONCLUSIONS: Baricitinib did not increase the incidence of adverse reactions. At the same time, we can find that it reduces the mortality of COVID-19 patients, not including the critically ill.


Assuntos
Azetidinas , COVID-19 , Humanos , Adulto , Estado Terminal , Tratamento Farmacológico da COVID-19 , Azetidinas/efeitos adversos
17.
Medicina (Kaunas) ; 59(11)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38004029

RESUMO

Background and Objectives: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis and a predictor of cardiovascular and cerebral events. The effects of ezetimibe on CIMT have been inconsistently reported. The aim of this meta-analysis is to compare the effects of ezetimibe/statin and statin alone therapies on CIMT reduction. Materials and Methods: The PubMed, Embase, and Cochrane library databases were searched for randomized controlled trials (RCTs) published prior to 26 January 2023 with the MeSH keywords 'Ezetimibe' and 'Carotid Intima-Media Thickness'. The results were presented as standard mean difference (SMD) with 95% confidence intervals using the random-effect model method, and heterogeneity was assessed. Subgroup, meta-regression, and sensitivity analyses were conducted. Results: Five RCTs with 642 participants were included. CIMT reduction was not significantly different between the ezetimibe/statin and statin alone groups. However, in subgroup analyses, CIMT in the ezetimibe/statin group was significantly reduced in patients with non-familial hypercholesterolemia (SMD: -0.34 mm and p = 0.002) and in patients with secondary prevention (SMD: -0.38 mm and p = 0.002). The low-density lipoprotein cholesterol level was significantly reduced in the ezetimibe/statin group (SMD: -0.58 mg/dL and p < 0.001). Conclusions: The effect of ezetimibe on CIMT reduction was shown in non-familial hypercholesterolemia and secondary prevention. These results suggest that the efficacy of ezetimibe may vary with potential CIMT reduction benefits in certain subpopulations.


Assuntos
Anticolesterolemiantes , Azetidinas , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ezetimiba/uso terapêutico , Espessura Intima-Media Carotídea , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , LDL-Colesterol , Ensaios Clínicos Controlados Aleatórios como Assunto , Quimioterapia Combinada
18.
Medicine (Baltimore) ; 102(47): e36122, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013289

RESUMO

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.


Assuntos
Anticolesterolemiantes , Azetidinas , Ácidos Heptanoicos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Humanos , Atorvastatina/uso terapêutico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol , Hipercolesterolemia/tratamento farmacológico , Azetidinas/uso terapêutico , Ácidos Heptanoicos/efeitos adversos , Pirróis/uso terapêutico , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Colesterol , Resultado do Tratamento , Método Duplo-Cego , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
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