RESUMEN
This post hoc analysis and modeling study examined the mechanism of action of odanacatib using a statistical model to explain sCTx response in ODN-treated patients as a function of other bone-turnover biomarkers that, with other observed biomarker changes, showed that odanacatib persistently inhibited osteoclastic bone removal activity without preventing osteoclastogenesis. INTRODUCTION: Odanacatib (ODN) is an oral selective cathepsin K (CatK) inhibitor, previously in development for osteoporosis treatment. A post hoc analysis examined ODN's mechanism of action on bone-turnover biomarkers. METHODS: A subset of patients who completed 60 months' treatment in the Long-Term Odanacatib Fracture Trial (LOFT; NCT00529373) (N = 112 [57 ODN, 55 placebo]) were evaluated. Serum (s) and urine (u) samples were assayed at baseline and months 6-60 for 10 known bone-remodeling biomarkers: sCTx, uαα- and ußßCTx/Cr, uNTx/Cr, sNTx, uDPD/Cr, sICTP, sTRAP5b, sPINP, and sBSAP. Because the CrossLaps® CTx assay identifies the CTx peptide as well as larger molecular weight CTx-containing peptides, including ICTP, a best-fit model was developed to explain the transient sCTx reduction in ODN-treated patients. RESULTS: ODN persistently reduced the bone-resorption markers sNTx, uNTx/Cr, uαα- and ußßCTx/Cr, and uDPD/Cr, and gradually increased the target-engagement marker sICTP and osteoclast number (sTRAP5b), versus placebo from baseline to month 60. sCTx was transiently reduced with ODN within 12 months, returning to baseline by month 48. Modeling suggested that sCTx changes in the ODN group were primarily due to increased accumulation of larger CTx species, including sICTP. The bone-formation markers sPINP and sBSAP showed partial reductions, versus placebo, in the first 6 months but approached baseline by months 48-60. CONCLUSION: Observed changes in bone-turnover biomarkers support the persistent efficacy of ODN in direct inhibition of osteoclastic bone-resorption activity, without inhibition of osteoclastogenesis. Long-term evaluation also underscores the unique mechanism of ODN on osteoclastic collagen processing and subsequently osteoblastic bone formation. TRIAL REGISTRATION: NCT00529373.
Asunto(s)
Conservadores de la Densidad Ósea , Resorción Ósea , Osteoporosis Posmenopáusica , Biomarcadores , Compuestos de Bifenilo/uso terapéutico , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Resorción Ósea/inducido químicamente , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Catepsina K , Femenino , Humanos , Osteoporosis Posmenopáusica/inducido químicamente , Osteoporosis Posmenopáusica/tratamiento farmacológico , PosmenopausiaRESUMEN
INTRODUCTION: Since the outbreak of COVID-19, measures were taken to protect healthcare staff from infection, to prevent infection of patients admitted to the hospital and to distribute PPE according to need. To assure the proper protection without overuse of limited supply of these equipments, screening of patients before surgical or diagnostic procedure was implemented. This study evaluates the results of this screening. METHOD: All patients screened for COVID-19 before procedure warranting either general, locoregional anaesthesia or sedation were included. Screening included a symptom questionnaire by phone, PCR and HRCT chest testing. Surgical or procedural details were registered together with actions taken based on screening results. RESULTS: Three hundred ninety-eight screenings were performed on 386 patients. The symptom questionnaire was completed in 72% of screenings. In 371 screenings, PCR testing was performed and negative. HRCT chest found 18 cases where COVID-19 could not be excluded, with negative PCR testing. Three patients had their surgery postponed due to inconclusive screening, and additional measures were taken in three other patients. There were incidental findings in 14% of HRCT chest scans. DISCUSSION: Pre-operative screening will differentiate if PPE is needed for procedures and which patients can safely have elective surgery during this COVID-19 pandemic and in the times to come. HRCT chest has no additional value in the pre-operative screening of asymptomatic patients. Screening can be performed with a symptom questionnaire, and additional screening with PCR testing in high-risk patient groups should be considered.
Asunto(s)
Infecciones Asintomáticas , Betacoronavirus , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Pruebas Diagnósticas de Rutina , Procedimientos Quirúrgicos Electivos , Tamizaje Masivo/métodos , Neumonía Viral/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Femenino , Humanos , Control de Infecciones/instrumentación , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Equipo de Protección Personal , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2 , Adulto JovenAsunto(s)
Prueba de Ácido Nucleico para COVID-19 , Prueba de COVID-19 , COVID-19/diagnóstico , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Cuidados Preoperatorios/métodos , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Anestesia , Infecciones Asintomáticas , COVID-19/transmisión , Humanos , AnamnesisRESUMEN
AIMS: The objective was to assess the consistency of effect of switching to ezetimibe/simvastatin 10/20 mg versus doubling the baseline statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg across subgroups of subjects with (n = 617) and without (n = 191) metabolic syndrome (MetS). METHODS: This was a post hoc analysis of a randomized, double-blind, 6-week study of adults 18-79 years with cardiovascular disease and diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. The percent change in LDL-C and other lipids was estimated within each subgroup separately. Safety and tolerability were assessed. RESULTS: In subjects with MetS, percent changes in LDL-C and other lipids were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin, except high-density lipoprotein cholesterol and apolipoprotein (Apo) AI (mean percent changes in LDL-C were: -22.49% ezetimibe/simvastatin, -9.64% doubled baseline statin and -19.20% rosuvastatin). In subjects without MetS, percent changes in LDL-C, total cholesterol and Apo B were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin (mean percent changes in LDL-C were: -25.14% ezetimibe/simvastatin, -4.75% doubled baseline statin and -19.75% rosuvastatin). Safety profiles were generally similar. CONCLUSION: These results showed that switching to ezetimibe/simvastatin 10/20 mg was more effective at reducing LDL-C, total cholesterol and Apo B versus doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg regardless of MetS status. These results were generally similar to those of the full cohort.
Asunto(s)
Azetidinas/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , LDL-Colesterol/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Simvastatina/uso terapéutico , Adolescente , Adulto , Anciano , Anticolesterolemiantes/uso terapéutico , Apolipoproteínas B/sangre , Apolipoproteínas B/efectos de los fármacos , Atorvastatina , Glucemia/efectos de los fármacos , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/prevención & control , Método Doble Ciego , Esquema de Medicación , Combinación de Medicamentos , Quimioterapia Combinada , Combinación Ezetimiba y Simvastatina , Ayuno , Femenino , Fluorobencenos/uso terapéutico , Ácidos Heptanoicos/uso terapéutico , Humanos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Rosuvastatina Cálcica , Sulfonamidas/uso terapéutico , Resultado del TratamientoRESUMEN
AIMS: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg vs. rosuvastatin (ROSUVA) 10 mg. METHODS: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) > or = 2.59 and < or = 4.92 mmol/l] and with high cardiovascular risk who were taking a stable daily dose of one of several statin medications for > or = 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation/screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose/potency, patients were randomised to EZE/SIMVA 10/20 mg (n = 314) or ROSUVA 10 mg (n = 304) for 6 weeks. RESULTS: EZE/SIMVA produced greater reductions in LDL-C (-27.7% vs. -16.9%; p < or = 0.001), total cholesterol (-17.5% vs. -10.3%; p < or = 0.001), non-high-density lipoprotein cholesterol (HDL-C) (-23.4% vs. -14.0%; p < or = 0.001) and apolipoprotein B (-17.9% vs. -9.8%; p < or = 0.001) compared with ROSUVA, while both treatments were equally effective at increasing HDL-C (2.1% vs. 3.0%; p = 0.433). More patients achieved LDL-C levels < 2.59 mmol/l (73% vs. 56%), < 2.00 mmol/l (38% vs. 19%) and < 1.81 mmol/l (25% vs. 11%) with EZE/SIMVA than ROSUVA (p < or = 0.001). A borderline significantly greater reduction in triglycerides (p = 0.056) was observed for EZE/SIMVA (-11.0%) vs. ROSUVA (-5.3%). There were no between-group differences in the incidences of adverse events or liver transaminase and creatine kinase elevations. CONCLUSION: EZE/SIMVA 10/20 mg produced greater improvements in LDL-C, total cholesterol, non-HDL-C and apoB with a similar safety profile as for ROSUVA 10 mg.
Asunto(s)
Azetidinas/uso terapéutico , Enfermedad de la Arteria Coronaria/prevención & control , Fluorobencenos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Pirimidinas/uso terapéutico , Simvastatina/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Azetidinas/efectos adversos , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Ezetimiba , Femenino , Fluorobencenos/efectos adversos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Persona de Mediana Edad , Pirimidinas/efectos adversos , Factores de Riesgo , Rosuvastatina Cálcica , Simvastatina/efectos adversos , Sulfonamidas/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of the study was to compare the efficacy/safety of doubling the dose of low-, medium- and high-potency statins on lipids/lipoproteins versus ezetimibe/simvastatin (EZE/SIMVA) 10/40 mg in patients with a recent coronary event. METHODS: In this open-label study, patients were stratified by baseline statin therapy (low, medium and high potency) and randomized equally to statin dose doubling or EZE/SIMVA 10/40 mg for 12 weeks. Primary analysis concerned change in low-density lipoprotein cholesterol for the whole population. Treatment-by-stratum interaction evaluated the consistency of treatment effect across statin potency strata. Post hoc analysis of between-group efficacy within strata was performed using ANCOVA. RESULTS: Within each stratum, EZE/SIMVA produced significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and non-high-density lipoprotein cholesterol (HDL-C) compared to statin doubling. Numerical trends toward smaller between-group reductions were observed with higher-potency statins and reached statistical significance for apolipoprotein B and non-HDL-C. No significant between-group differences in HDL-C and C-reactive protein were observed within each stratum. EZE/SIMVA produced larger reductions in triglycerides versus low-potency statin, whereas it was similarly effective compared with intermediate-/high-potency statins. The safety/tolerability profiles of the treatments were similar across the strata. CONCLUSIONS: EZE/SIMVA 10/40 mg produced greater improvements in lipids with a similar safety profile compared to doubling the dose of low-, medium- and high-potency statins.
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Azetidinas/administración & dosificación , Enfermedad Coronaria/etiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/complicaciones , Hipercolesterolemia/tratamiento farmacológico , Simvastatina/administración & dosificación , Anciano , Angina Inestable/etiología , Anticolesterolemiantes/efectos adversos , Apolipoproteínas B/sangre , Azetidinas/efectos adversos , Proteína C-Reactiva/metabolismo , HDL-Colesterol/sangre , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Combinación Ezetimiba y Simvastatina , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Persona de Mediana Edad , Simvastatina/efectos adversosRESUMEN
BACKGROUND: The aim of this study was to investigate the efficacy and safety profile of switching to ezetimibe/simvastatin (Eze/Simva) 10/40 mg compared with doubling the statin dose upon discharge in patients taking a statin and admitted to the hospital for the investigation of a coronary event. DESIGN: This phase IV, multi-centre, randomised, open-label, active-controlled, parallel group study enrolled 424 patients (aged >/= 18 years) hospitalised for an acute coronary event and taking a stable dose of a statin (>/= 6 weeks) that could be doubled per the product label. Upon discharge from the hospital, patients were stratified by their statin dose/potency (high, medium and low) and randomised 1 : 1 to doubling of the statin dose (n = 211) or Eze/Simva 10/40 mg (n = 213) for 12 weeks. The primary efficacy variable was the absolute low-density lipoprotein cholesterol (LDL-C) value (mmol/l) at study end-point. RESULTS: Mean baseline LDL-C for the two treatment groups were 2.48 and 2.31 mmol/l for the Eze/Simva and statin groups respectively. At study end-point, least squares mean LDL-C values were 1.74 mmol/l in the Eze/Simva group and 2.22 mmol/l in the statin group resulting in a significant between-group difference of -0.49 mmol/l (p = 0.001). Eze/Simva 10/40 mg also produced significantly lower total cholesterol (-0.49 mmol/l), non-high-density lipoprotein cholesterol [(non-HDL-C); -0.53 mmol/l] and apolipoprotein B (-0.14 mmol/l) values compared with doubling the statin dose (p = 0.001 for all). Both treatments produced similar effects on triglycerides, C-reactive protein and HDL-C; the between treatment group differences were not significant (p >/= 0.160). Significantly more patients achieved LDL-C levels < 2.5 (< 100 mg/dl; 86% vs. 72%), < 2.0 (< 77 mg/dl; 70% vs. 42%) and < 1.8 mmol/l (< 70 mg/dl; 60% vs. 31%) with Eze/Simva than statin (all p = 0.001). Eze/Simva was generally well tolerated, with a safety profile similar to statin. There were no differences in the incidences of liver transaminases >/= 3 x upper limit of normal (ULN) or creatine kinase >/= 10 x ULN between the groups. CONCLUSIONS: In patients taking a statin and admitted to the hospital for investigation of a coronary event, treatment with Eze/Simva 10/40 mg for 12 weeks produced greater improvements in lipids with a similar safety profile compared with doubling of the statin dose.
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Azetidinas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Simvastatina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Ezetimiba , Hospitalización , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
AIM: This randomized, double-blind study evaluated the efficacy of switching from atorvastatin (ATV) 10 mg to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg, EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes (T2D). METHODS: Eligible patients had haemoglobin A(1C)< or =10%, were aged > or =18 years and were on ATV 10 mg for > or =6 weeks before study entry. After a 4-week open-label ATV 10 mg run-in, patients were randomized to EZE/SIMVA 10/20 mg (n = 220), EZE/SIMVA 10/40 mg (n = 222) or ATV 20 g (n = 219) daily for 6 weeks. RESULTS: Greater (p < or = 0.001) reductions in low-density lipoprotein cholesterol (LDL-C) (the primary end-point) were achieved by switching to EZE/SIMVA 10/20 mg (26.2%) or 10/40 mg (30.1%) than by doubling the dose of ATV to 20 mg (8.5%). EZE/SIMVA 10/20 mg and 10/40 mg produced greater (p < or = 0.001) reductions in total cholesterol, non-high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B relative to ATV 20 mg. A reduction (p < or = 0.050) in C-reactive protein was observed with EZE/SIMVA 10/40 mg vs. ATV 20 mg. Similar reductions in triglycerides were observed across the three groups, and none of the treatments produced a significant change in HDL-C. A greater (p < or = 0.001) proportion of patients achieved LDL-C <2.5 mmol/l with EZE/SIMVA 10/20 mg (90.5%) and 10/40 mg (87.0%) than with ATV 20 mg (70.4%). Both EZE/SIMVA doses were generally well tolerated, with an overall safety profile similar to ATV 20 mg. CONCLUSIONS: EZE/SIMVA 10/20 and 10/40 mg provided greater lipid-altering efficacy than doubling the dose of ATV from 10 to 20 mg and were well tolerated in patients with T2D.
Asunto(s)
Azetidinas/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ácidos Heptanoicos/uso terapéutico , Pirroles/uso terapéutico , Simvastatina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anticolesterolemiantes/uso terapéutico , Atorvastatina , Índice de Masa Corporal , Colesterol/sangre , Enfermedad Coronaria/prevención & control , Angiopatías Diabéticas/prevención & control , Método Doble Ciego , Ezetimiba , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
STUDY DESIGN: An open-label, multicentre study was conducted to evaluate the antihypertensive efficacy of a 4-week course of losartan 50 mg plus hydrochlorothiazide 12.5 mg in Asian patients with essential hypertension whose blood pressure had previously been treated with but not controlled by valsartan 80 mg. METHODS: A total of 237 eligible patients with mean trough sitting diastolic blood pressure (SiDBP) 95-115 mmHg and a mean trough sitting systolic blood pressure (SiSBP) < 190 mmHg entered the baseline period of treatment with valsartan 80 mg/day for 4 weeks. Those (n = 165) whose SiDBP remained > 90 mmHg and who were not excluded for other reasons were then switched to a single-tablet formulation of losartan 50 mg/hydrochlorothiazide 12.5 mg combination once daily for a further 4 weeks. RESULTS: Mean SiDBP (study primary endpoint) at the end of combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions after switching from valsartan 80 mg to losartan 50 mg/hydrochlorothiazide 12.5 mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively (p < or = 0.001 for both outcomes). The goal of SiDBP < or = 90 mmHg was attained in 72% of the patients previously not controlled to the same level by valsartan 80 mg/day. Combination therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg was generally well tolerated. Mean compliance with the losartan 50 mg/hydrochlorothiazide 12.5 mg combination was > 99%. CONCLUSION: These results demonstrate that in Asian patients who do not reach the goal of mean trough SiDBP < or = 90 mmHg with valsartan monotherapy at 80 mg once-daily, switching to a single-tablet combination of losartan 50 mg/hydrochlorothiazide 12.5 mg once-daily is well tolerated, provides effective control of blood pressure and is an excellent choice to achieve blood pressure reduction goals.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Losartán/uso terapéutico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Adulto , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antihipertensivos/administración & dosificación , Pueblo Asiatico , Combinación de Medicamentos , Femenino , Humanos , Losartán/administración & dosificación , Masculino , Persona de Mediana Edad , Inhibidores de los Simportadores del Cloruro de Sodio/administración & dosificación , Tetrazoles/uso terapéutico , Valina/análogos & derivados , Valina/uso terapéutico , ValsartánRESUMEN
Preference is a composite, patient-oriented endpoint incorporating efficacy, tolerability, formulation, and convenience of medications. The objective of this study was to compare patient preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute treatment of migraine. In this multicentre, open-label, two-period, crossover study, out-patients were randomly assigned to treat the first of two moderate to severe migraines with rizatriptan or eletriptan and the second with the alternate therapy. Patients completed diary assessments at baseline and up to 24 h after taking study medication. At the last visit, patients completed a psychometrically validated preference questionnaire. A total of 372 patients (mean age 38 years, 85% female) treated two migraine attacks, and 342 patients (92%) expressed a preference for treatment. Significantly more (P < or = 0.001) patients preferred rizatriptan 10-mg wafer [61.1%; 95% confidence interval (CI) 55.7, 66.3] to eletriptan 40-mg tablet (38.9%; 95% CI 33.7, 44.3). The most common reason given for preference of either treatment was speed of headache relief. At 2 h, 80% and 69% of patients reported that rizatriptan and eletriptan, respectively, was convenient or very convenient to take (mean convenience score 1.99 vs. 2.31, respectively; P < or = 0.001). Both triptans were well tolerated. In this head-to-head study designed to evaluate global patient preference, significantly more patients preferred the rizatriptan 10-mg wafer to the eletriptan 40-mg tablet for acute treatment of migraine. The single most important reason for preference was speed of relief, consistent with results from previous preference studies.
Asunto(s)
Trastornos Migrañosos/tratamiento farmacológico , Pirrolidinas/administración & dosificación , Agonistas de Receptores de Serotonina/administración & dosificación , Triazoles/administración & dosificación , Triptaminas/administración & dosificación , Administración Oral , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Comprimidos , Factores de TiempoRESUMEN
This randomised, double-blind study evaluated the efficacy and safety of ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg tablet compared to doubling the atorvastatin (ATV) dose in hypercholesterolaemic patients with atherosclerotic or coronary heart disease (CHD). The study group included 435 male and female CHD patients (aged >or=18 years) who had not achieved their low-density lipoprotein cholesterol (LDL-C) goal of <2.50 mmol/l while on a stable dose of ATV 10 mg for >or=6 weeks. After a 1-week diet/stabilisation period, patients with LDL-C >or=2.50 mmol/l and Asunto(s)
Anticolesterolemiantes/administración & dosificación
, Azetidinas/administración & dosificación
, Ácidos Heptanoicos/administración & dosificación
, Hipercolesterolemia/tratamiento farmacológico
, Pirroles/administración & dosificación
, Simvastatina/administración & dosificación
, Adulto
, Anciano
, Anciano de 80 o más Años
, Apolipoproteínas B/sangre
, Aterosclerosis/complicaciones
, Aterosclerosis/tratamiento farmacológico
, Atorvastatina
, HDL-Colesterol/sangre
, LDL-Colesterol/sangre
, Enfermedad Coronaria/complicaciones
, Enfermedad Coronaria/tratamiento farmacológico
, Método Doble Ciego
, Quimioterapia Combinada
, Europa (Continente)
, Ezetimiba
, Femenino
, Humanos
, Hipercolesterolemia/complicaciones
, Masculino
, Persona de Mediana Edad
, Taiwán
, Resultado del Tratamiento
RESUMEN
This randomised, double-blind, placebo (PBO)-controlled study evaluated the efficacy and safety of ezetimibe (EZE) co-administered with ongoing atorvastatin (ATV) therapy in 450 hypercholesterolemic patients with coronary heart disease (CHD) who had not achieved their low-density lipoprotein cholesterol (LDL-C) goal < or =2.60 mmol/l while on a stable dose of ATV 10 or 20 mg/day for > or =6 weeks. After a 4-week diet/baseline active run-in period, patients with LDL-C >2.60 mmol/l and < or =4.20 mmol/l were stratified by ATV dose and randomised (1 : 1) to EZE 10 mg or PBO for 6 weeks while continuing open-label ATV. Significantly more patients achieved an LDL-C goal < or =2.6 mmol/l with EZE than PBO (81.3 vs. 21.8%; p < or = 0.001). Compared to PBO, co-administration of EZE with ongoing ATV led to significantly (p < or = 0.001) greater reductions in LDL-C, total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B; HDL-C was significantly (p < or = 0.05) increased. Co-administration of EZE and ATV was well tolerated, with an overall safety profile similar to ATV alone.
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Azetidinas/administración & dosificación , Enfermedad Coronaria/tratamiento farmacológico , Ácidos Heptanoicos/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Pirroles/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anticolesterolemiantes/efectos adversos , Atorvastatina , Azetidinas/efectos adversos , LDL-Colesterol/sangre , Método Doble Ciego , Quimioterapia Combinada , Ezetimiba , Femenino , Ácidos Heptanoicos/efectos adversos , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Pirroles/efectos adversos , SeguridadRESUMEN
OBJECTIVE: To evaluate the addition of ezetimibe or placebo to on-going simvastatin treatment on attaining the LDL-C treatment target of = 2.60 mmol/L (100 mg/dL) in coronary heart disease (CHD) patients with hypercholesterolemia. METHODS: Patients with documented CHD were recruited if they were on a stable dose of simvastatin 10 mg or 20 mg for at least 6 weeks, had LDL-C > 2.60 mmol/L and = 4.20 mmol/L (> 100 mg/dL and = 160 mg/dL), triglycerides = 4.00 mmol/L (355 mg/dL) and hepatic transaminases and creatine kinase = 50% above the upper limit of normal. After a 4-week placebo and diet run-in period, eligible patients were randomized to a double-blind, placebo-controlled comparative study with ezetimibe 10mg co-administered with on-going simvastatin 10mg or 20 mg (n = 208) versus placebo to match ezetimibe co-administered with simvastatin 10mg or 20mg for 6 weeks (n = 210). RESULTS: When ezetimibe was added to on-going simvastatin therapy, a significantly greater percentage of patients attained the LDL-C target of = 2.60 mmol/L after 6 weeks of treatment compared to placebo added to on-going simvastatin (80.4% vs. 17.4%, respectively;p = 0.001). When co-administered with on-going simvastatin therapy, mean percentage reduction in LDL-C from baseline was significantly larger in the ezetimibe group compared to placebo (27.1% vs. 4.1%, respectively; p = 0.001). The co-administration of ezetimibe or placebo to on-going simvastatin treatment was generally well tolerated. CONCLUSIONS: Ezetimibe co-administered with on-going simvastatin 10 mg or 20 mg treatment enabled more CHD patients with hypercholesterolemia to attain the LDL-C treatment target of = 2.60 mmol/L.