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1.
Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe 总被引:2,自引:0,他引:2
Lowering serum cholesterol levels reduces the risk of coronary heart disease (CHD)-related events. Statins are commonly prescribed as first-line treatment but many patients at high-risk for CHD still fail to reach their cholesterol or low-density lipoprotein cholesterol (LDL-C) goals with statin monotherapy. National and international guidelines for the prevention of CHD recommend the modification of lipid profiles and particularly LDL-C [e.g. the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III; 2001) and Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (2003) Guidelines]. Several recent clinical trials indicated an added benefit from aggressive lowering of LDL-C levels. Based on these findings, the NCEP ATP III revised the LDL-C target from < 100 mg/dL (2.6 mmol/L) to < 70 mg/dL (1.8 mmol/L) (optional target) for very high-risk patients and < 130 mg/dL (3.4 mmol/L) to < 100 mg/dL (2.6 mmol/L) for moderately high-risk patients. For patients who fail to achieve their LDL-C target, inhibiting the two main sources of cholesterol - synthesis and uptake - can produce more effective lipid lowering, allowing more patients to reach their LDL-C goal. Ezetimibe is a highly-selective inhibitor of cholesterol absorption and simvastatin is an evidence-based inhibitor of cholesterol synthesis. The LDL-C-lowering efficacy of targeting both major sources of cholesterol with ezetimibe plus simvastatin was demonstrated in several multicentre, double-blind, placebo-controlled trials in patients with hypercholesterolaemia. For patients who do not reach their cholesterol goal with a statin, adding ezetimibe 10 mg significantly reduces LDL-C compared with statin monotherapy. Thus, this treatment option may help patients reach the new 'stricter' cholesterol goals. This review, based on a Medline database search from January 2000 to August 2005, considers the LDL-C-lowering efficacy of ezetimibe and discusses the role of this agent for patients who fail to achieve guideline cholesterol goals with statin monotherapy. 相似文献
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《Current medical research and opinion》2013,29(4):713-719
ABSTRACTObjective: Patients with primary hypercholesterolaemia and concomitant coronary heart disease (CHD) and/or diabetes mellitus (DM), who are at particularly high risk of cardiovascular events such as stroke or myocardial infarction, benefit from aggressive lipid lowering strategies. The present studies investigated the incremental efficacy and safety of dual cholesterol inhibition with ezetimibe/simvastatin in such high-risk patients pre-treated with statins but not reaching the 100?mg/dL (2.6?mmol/L) low density cholesterol (LDL?C) cholesterol threshold in the primary care setting.Methods: Two open-label, prospective, non-randomised, observational studies (study 1 with n = 19?194 patients, predominantly with CHD; study 2 with n = 19?484 patients, predominantly with DM). Patients received – almost all after statin pre-treatment – ezetimibe 10?mg plus simvastatin 10?mg (study 1: 15%, study 2: 16%), 20?mg (in 68% each), 40?mg (12%/10%) or 80?mg (1%/1%) as fixed dose combinations over 3 months (dosage at investigator's discretion).Results: Mean LDL-C was reduced by 28%/27% (study 1/ study 2) compared with baseline values (on statin monotherapy). Mean total cholesterol was decreased by 22% in each study, mean triglycerides by 16/17%, and mean high density cholesterol (HDL?C) was increased by 9/10%. Adverse events were reported in 0.3% and 0.2% of patients, respectively.Conclusion: Dual cholesterol inhibition with ezetimibe/simvastatin was effective and well tolerated under real practice conditions in high-risk patients with CHD and/or DM. 相似文献
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《Current medical research and opinion》2013,29(9):2183-2192
ABSTRACTBackground: Recent guidelines underline the need for high-risk patients to reach strict low density lipoprotein cholesterol (LDL?C) targets (1.8–2.6?mmol/L; 70–100?mg/dL), and specifically mention the possible use of combination therapy (e.g. statin + ezetimibe) to achieve these goals.Methods: A retrospective case-note audit was carried out to assess the response to administering ezetimibe in patients unable to tolerate statins (Group 1), or high dose of statins (Group 2) and patients who cannot achieve the LDL?C target (2.6?mmol/L; 100?mg/dL) despite taking a statin (Group 3).Results: Ezetimibe lowered LDL?C levels by 20–29% across the 3 patient groups after 2–3 months of treatment. High density lipoprotein cholesterol (HDL?C) levels tended to remain unchanged, although there was a consistent trend for a fall if baseline values were ‘high’. However, the LDL-C/HDL-C ratio changed significantly and favourably in all groups. The fall in fasting triglyceride levels in all groups was greater (reaching 19–25%) when baseline levels were ≥ 1.5 or 1.7?mmol/L (136–150?mg/dL). There were no marked abnormalities in liver function tests or creatine kinase activity. In Group 3 there was a significant trend for a fall in serum creatinine levels across the tertiles of baseline creatinine values.Limitations of the present study include the small sample size (especially in Groups 1 and 2), its short-term duration and the absence of event-based end-points. Therefore, the results are hypothesis-generating rather than conclusive.Conclusions: When used alone or added to a statin, ezetimibe favourably altered the LDL?C/HDL?C ratio and lowered triglyceride levels. Ezetimibe was well tolerated in patients with statin intolerance and was associated with a 26% fall in LDL?C. An additional action may be some degree of improved renal function. Further studies are needed to confirm these findings. 相似文献
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《Current medical research and opinion》2013,29(4):767-775
ABSTRACTObjective: Combination of ezetimibe (EZE) with a statin represents an attractive strategy for cholesterol-lowering treatment, as it inhibits the two main sources of cholesterol: absorption from the intestine (inhibited by EZE) and endogenous biosynthesis (inhibited by statins).Research design and methods: This multicentre, double-blind, placebo-controlled study randomised a total of 148 men and women with primary hypercholesterolaemia and coronary heart disease (CHD) to receive treatment for 6 weeks with either EZE 10?mg + atorvastatin 10?mg (EZE + ATV; n = 72) or placebo/atorvastatin 10?mg (ATV; n = 76). The primary efficacy variable was the mean percentage change in low-density lipoprotein cholesterol (LDL?C) from baseline to study endpoint.Results: At 6 weeks, EZE + ATV provided a significantly greater adjusted mean change from baseline in LDL?C compared with ATV monotherapy (–50.5% vs. –36.5%; p < 0.0001), equating to an additional 14.1% reduction (95% CI –17.90, –10.19) in LDL?C. A significantly higher proportion of patients on EZE + ATV achieved the new Joint British Societies (JBS 2) recommended LDL?C goal of < 2?mmol/L (62% vs. 12% with ATV alone; p < 0.0001) and the JBS 2 minimum treatment standard of < 3?mmol/L (93% vs. 79% with ATV alone). Patients receiving EZE + ATV were 12 times more likely to reach LDL?C targets (odds ratio 12.1; 95% CI 5.8, 25.1; p < 0.0001) compared with patients receiving ATV monotherapy. Clinical chemistry profiles and the incidence of adverse events were similar in both groups.Conclusions: Adding EZE to ATV monotherapy represents an attractive and well-tolerated treatment option to bring patients at high risk of CHD to the aggressive LDL?C goals recommended by recent treatment guidelines. 相似文献
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《Current medical research and opinion》2013,29(8):2009-2026
ABSTRACTObjective: To review and analyse the evidence for the cholesterol-lowering effect of ezetimibe in adult patients with hypercholesterolaemia who are not at low-density lipoprotein cholesterol (LDL?C) goal on statin monotherapy.Research design: Systematic review and meta-analysis.Methods: MEDLINE and EMBASE were searched to identify ezetimibe randomised controlled trials (RCTs) published between January 1993 and December 2005. The meta-analysis combined data from RCTs, with a minimum treatment duration of 6 weeks, that compared treatment with ezetimibe 10?mg/day or placebo added to current statin therapy.The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in total cholesterol (TC), LDL?C, and high-density lipoprotein cholesterol (HDL?C), and number of patients achieving LDL?C treatment goal. Meta-analysis results are presented for a modified version of the inverse variance random effects model.Results: Five RCTs involving a total of 5039 patients were included in the meta-analysis. The weighted mean difference (WMD) between treatments significantly favoured the ezetimibe/statin combination over placebo/statin for TC (–16.1% (–17.3, –14.8); p < 0.0001), LDL?C (–23.6% (–25.6, –21.7); p < 0.0001) and HDL?C (1.7% (0.9, 2.5); p < 0.0001). The relative risk of reaching the LDL?C treatment goal was significantly higher for patients on ezetimibe/statin relative to those on placebo/statin (3.4 (2.0, 5.6); p < 0.0001). In pre-defined sub-group analyses of studies in patients with coronary heart disease, the WMD between treatments remained significantly in favour of ezetimibe/statin (?p < 0.0001) for TC and LDL?C but was no longer significant for HDL?C. Elevations in creatine kinase, alanine aminotransferase or aspartate aminotransferase that were considered as an adverse effect did not differ significantly between treatments.Conclusions: The meta-analysis we performed included only five studies and was restricted to analysis of the changes in cholesterol levels relative to baseline. However, the results suggest that ezetimibe co-administered with ongoing statin therapy provides significant additional lipid-lowering in patients not at LDL?C goal on statin therapy alone, allowing more patients to reach their LDL?C goal. 相似文献
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《Current medical research and opinion》2013,29(8):1821-1827
ABSTRACTBackground: Hypercholesterolaemia is one of the major risk factors for the development of coronary heart disease (CHD). European guidelines emphasize the importance of reducing low-density lipoprotein cholesterol (LDL?C) levels below 115?mg/dL (3.0?mmol/L) in patients with high CHD risk.Objective: The present study evaluates whether selection of the atorvastatin starting dose based on baseline LDL?C levels and previous statin treatment status would result in an achievement of LDL?C targets without the need for up-titration.Methods: A multicentre, prospective, open-label study conducted in Belgium. Patients were at high risk defined as either a history of CHD, another atherosclerotic disease, diabetes mellitus Type 2 or an estimated 10?year CHD risk > 20%. The primary endpoint was the proportion of patients achieving the LDL?C goal after 12 weeks of treatment.Results: Overall, 96.4% of the 195 statin-naïve patients reached the LDL?C target after 12 weeks of treatment. The majority of the patients (95.4%) already reached LDL?C control at Week 6. Mean (SD) LDL?C levels decreased from 159 (25)?mg/dL[(4.1 (0.6)?mmol/L] to 86 (14)?mg/dL [2.2 (0.4)?mmol/L] after 12 weeks of treatment. Only 4.6% of the patients needed an up-titration at Week 6.Conclusions: Taken together, the results demonstrate that LDL?C based dose selection of atorvastatin is highly efficacious for rapid achievement of target LDL?C levels with a low need for up-titration. Application of this flexible first dosing strategy in general practice will, based on available evidence, increase adherence to atorvastatin treatment in patients with high CHD risk. 相似文献
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《Current medical research and opinion》2013,29(3):685-694
ABSTRACTObjective: To assess the incremental low-density lipoprotein-cholesterol (LDL-C) lowering efficacy of doubling the statin dose or switching to the ezetimibe/simvastatin 10/20?mg combination tablet (EZE/SIMVA) in patients on simvastatin 20?mg or atorvastatin 10?mg not at LDL-C target < 2.5?mmol/L.Study design and methods: Patients with documented coronary heart disease (CHD) and/or type 2 diabetes (DM2) with LDL-C ≥ 2.5 and < 5.0?mmol/L despite treatment with atorvastatin 10?mg or simvastatin 20?mg were randomized to (1) double statin dose or (2) switch to ezetimibe/simvastatin 10/20, according to a PROBE study design. LDL-C, lipoprotein subfractions and safety data were assessed during the study.Results: 119 of 178 (67%) patients in the EZE/SIMVA group and 49 of 189 (26%) in the doubling statin group reached target LDL-C < 2.5?mmol/L. The odds ratio of success for EZE/SIMVA versus doubling statin treatment in reaching the LDL-C target of < 2.5?mmol/L was 5.7 (95% CI: 3.7–9.0, p < 0.0001). A reduction in total cholesterol (TC), total/high density lipoprotein (HDL) cholesterol ratio and apolipoprotein B was observed in both groups, but this reduction was significantly more pronounced in the EZE/SIMVA group as compared with the doubling statin dose group. Treatment was well tolerated and no difference was observed between the two groups with regard to adverse effects.Conclusions: In CHD/DM2 patients treated with simvastatin or atorvastatin with LDL-C persistently ≥ 2.5?mmol/L, switching to the EZE/SIMVA was more effective in attaining the LDL-C target of < 2.5?mmol/L than doubling the statin dose. 相似文献
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《Current medical research and opinion》2013,29(11):2191-2200
ABSTRACTObjective: The primary aim of this study was to compare the effect of colesevelam HCl in combination with ezetimibe to ezetimibe monotherapy on low-density lipoprotein cholesterol (LDL.C) levels in subjects with primary hypercholesterolemia.Methods: Subjects with primary hypercholesterolemia (N = 86) were enrolled in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a 4- to 8‐week washout period, subjects received colesevelam HCl 3.8?g/day plus ezetimibe 10?mg/day or colesevelam HCl placebo plus ezetimibe 10?mg/day for 6 weeks. The primary efficacy endpoint was the mean percent change in LDL‐C during randomized treatment. Secondary endpoints included mean absolute change in LDL‐C, mean absolute and mean percent change in levels of high-density lipoprotein cholesterol (HDL‐C), non-HDL‐C, total cholesterol (TC), apolipoprotein (apo) A-I and apo B, and median absolute and percent changes in triglycerides (TG) and high-sensitivity C‐reactive protein from baseline to end of treatment. Of the 86 subjects randomized to treatment, 85 were included in the intent-to-treat analysis.Results: After 6 weeks of treatment, colesevelam HCl plus ezetimibe produced a mean percent change in LDL‐C of –32.3% versus–21.4% with ezetimibe monotherapy (?p < 0.0001). Colesevelam HCl plus ezetimibe was significantly more effective than ezetimibe alone at producing mean percent reductions in TC, non‐HDL‐C, and apo B and increases in apo A-I (?p < 0.005 for all). Neither treatment regimen resulted in significant changes in median TG levels compared with baseline (?p = NS). Both treatments were safe and generally well tolerated.Conclusions: Colesevelam HCl plus ezetimibe combination therapy significantly reduced mean LDL‐C, TC, non-HDL‐C, and apo B levels and increased apo A-I levels (?p < 0.005 for all) without significantly increasing median TG levels in hypercholesterolemic subjects compared with ezetimibe alone. Although limited in that atherosclerotic coronary heart disease outcomes were not evaluated, this study demonstrated that combining colesevelam HCl with ezetimibe is a therapeutic option in hypercholesterolemic patients, such as those in whom statins are contraindicated and/or who may have intolerances to statin therapy. 相似文献
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《Current medical research and opinion》2013,29(9):1437-1445
SUMMARYObjective: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS).Research design and methods: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of adding ezetimibe 10?mg/day versus placebo to ongoing, open-label statin treatment for 8 weeks in hypercholesterolemic patients. Qualifying LDL-C levels and target LDL-C goals were based on National Cholesterol Education Program risk categories. The DM subgroup were patients who entered the study with a prior diagnosis of DM. Patients were classified as having MetS if they met 3 or more of the following criteria at baseline: triglycerides (TG) ≥ 150?mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) < 40?mg/dL (1.04 mmol/L) for men or < 50?mg/dL (1.29 mmol/L) for women; fasting serum glucose (FSG) ≥ 110?mg/dL (≥ 6.1 mmol/L); a diagnosis of hypertension or taking hypertension medication or blood pressure ≥ 130/ ≥ 85 mmHg; waist circumference > 88?cm (women) or > 102?cm (men). DM patients were excluded from the MetS subgroup analysis.Main outcome measures: The objectives were to assess the effects of treatment on plasma concentrations of LDL-C and other lipid variables, and on the percentage of patients achieving LDL-C target levels at the end of the study.Results: Of 769 patients enrolled in the original study, there were 191 (24.8%) with DM and 195 (25.4%) with MetS. Regardless of subgroup, ezetimibe + statin was significantly more effective than statin alone at lowering plasma levels of LDL-C, non-HDL-C, total cholesterol, apolipoprotein B, and triglycerides (between-group p < 0.001 for all). For all lipid parameters, the relative treatment effects were generally consistent regardless of DM or MetS status. Significantly more ezetimibe than placebo patients in all subgroups achieved prespecified LDL-C goals (?p < 0.001 for all), and although more patients in the DM and MetS groups, respectively, achieved the goal compared with their non-DM and non-MetS counterparts [83.6% (DM) versus 67.2 (non-DM) and 71.8% (MetS) versus 65.6% (non-MetS)], these differences were not significant after adjusting for differences in baseline LDL-C levels. Ezetimibe was well-tolerated and had a favorable safety profile in all subgroups.Conclusions: The co-administration of ezetimibe with statins, a therapeutic regimen that inhibits both the absorption and synthesis of cholesterol, offers a well-tolerated and efficacious treatment to lower LDL-C in patients with DM and MetS. 相似文献
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《Current medical research and opinion》2013,29(6):1659-1668
ABSTRACTObjective: To determine (a) the proportion of patients at high risk of cardiovascular events who achieve low-density lipoprotein cholesterol (LDL-C) goals as recommended by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) guidelines, and (b) the predictors of poor LDL-C control.Methods: Two open-label, prospective, non-randomised, observational studies (study 1 with n?=?19 194 patients, predominantly with coronary artery disease (CHD); study 2 with n?=?19 484 patients, predominantly with diabetes mellitus (DM)). Patients received, usually after statin pretreatment, ezetimibe 10?mg plus simvastatin as fixed-dose combinations over 3?months. Bivariate and multivariate regression analysis was performed to identify factors associated with poor LDL-C control.Results: At study end, 38?%?(up from 4.7?%?at baseline) of CHD and 35?%?(up from 3.3?%?at baseline) of diabetic patients achieved the target LDL value?<?100?mg/dl (2.6?mmol/l) after treatment with a fixed-dose ezetimibe–simvastatin combination. In both studies, concomitant atherosclerotic disease was associated with good control. Conversely, factors associated with poor control were, among others, high baseline LDL-C values, pretreatment with certain statins, and (in the DM study) high HbA1c, and high body mass index.Conclusion: Under real world, general practice conditions, a substantial proportion of high-risk patients with CHD and/or DM met LDL-C target levels on dual cholesterol inhibition with ezetimibe/simvastatin. A limited number of easily recognisable factors allow physicians to identify high risk patients whose LDL-C is likely to be difficult to control. Early identification of this patient group may have profound clinical benefits in general practice by enabling specific early interventions such as counselling on physical activity, dietary support and/or follow up visits to the GP. 相似文献
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《Current medical research and opinion》2013,29(1):249-259
ABSTRACTBackground: Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and ratios of these sterols to total cholesterol (TC) are reported to correlate with efficiency of intestinal cholesterol absorption, whereas levels of certain cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios to TC correlate with cholesterol biosynthesis. However, there is a paucity of published data concerning the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) on these parameters.Objectives: To characterize the effects of ezetimibe co-administered with statins, compared with each treatment alone, on cholesterol precursor sterols and plasma phytosterol levels.Methods: A post-hoc analysis was performed to determine the effects of treatment with ezetimibe 10?mg, simvastatin (10–80?mg), and atorvastatin (10–80?mg), alone or in combination, on these non-cholesterol sterols using plasma samples from two randomized controlled trials involving patients with primary hypercholesterolemia (low-density lipoprotein [LDL-C]?=?145–250?mg/dL; triglycerides ≤350?mg/dL; N?=?975) but without a recent (≤6-month) history of coronary heart disease (CHD) or either uncontrolled or newly diagnosed diabetes mellitus.Results: Ezetimibe monotherapy significantly reduced plasma sitosterol and campesterol concentrations from baseline compared with placebo (both p?<?0.001), whereas statins significantly lowered desmosterol and lathosterol levels (p?<?0.001 vs. placebo). Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these sterols (p?<?0.001).Conclusions: The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe–statin) doses and circulating non-cholesterol levels. 相似文献
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Dr Jean-Claude Ansquer Ivan Bekaert Martine Guy Markolf Hanefeld Alain Simon 《Am J Cardiovasc Drugs》2009,9(2):91-101
Background
Patients with type IIb, or mixed, dyslipidemia have high levels of low-density lipoprotein cholesterol (LDL-C) with predominance of small dense LDL particles, high levels of triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Fenofibrate significantly reduces TG and, more moderately, LDL-C, increases HDL-C and produces a shift from small to large LDL particle size; the main effect of ezetimibe is a reduction in LDL-C levels. Combined treatment with fenofibrate and ezetimibe may correct all the abnormalities of type IIb dyslipidemia.Objective
To assess the efficacy and safety of coadministration of fenofibrate (NanoCrystal®) and ezetimibe in patients with type IIb dyslipidemia and the metabolic syndrome compared with administration of fenofibrate and ezetimibe alone (ClinicalTrials.gov Identifier: NCT00349284; Study ID: CLF178P 04 01).Methods
This was a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Sixty ambulatory patients (mean age 56 years; 50% women, 50% men) were treated in each group. For inclusion in the study, patients were required to have LDL-C ≥4.13 mmol/L (≥ 160 mg/dL), TG ≥1.71 mmol/L and ≤4.57 mmol/L (≥150 mg/dL and ≤405 mg/dL), and at least two of the following National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome: low HDL-C or increased fasting plasma glucose, blood pressure, or waist circumference. Patients received fenofibrate 145 mg, ezetimibe 10 mg, or coadministration of both (fenofibrate/ezetimibe) daily for 12 weeks. The outcome measures were changes in lipids and related parameters, apolipoproteins, glucose metabolism parameters, and high-sensitivity C-reactive protein (hsCRP).Results
Fenofibrate/ezetimibe was more effective than either fenofibrate or ezetimibe in reducing LDL-C (?36.2% vs ?22.4% and ?22.8%, respectively), non-HDL-C (?36.2% vs ?24.8% and ?20.9%, respectively), total cholesterol (TC) [?27.9% vs ?18.9% and ?17.1%, respectively], apolipoprotein B (?33.3% vs ?24.5% and ?18.7%, respectively), TC/HDL-C ratio (?34.2% vs ?23.0% and ?17.0%, respectively), and apolipoprotein B/apolipoprotein AI ratio (?37.5% vs ?27.0% and ?17.7%, respectively) [p<0.001 for all comparisons between fenofibrate/ezetimibe and monotherapies]. Fenofibrate/ezetimibe was as effective as fenofibrate and more effective than ezetimibe in reducing remnant-like particle cholesterol (?36.2% and ?30.7% vs ?17.3%, respectively), and in increasing LDL size ( + 2.1% and + 1.9% vs + 0.7%, respectively), apolipoprotein AI (+7.9% and + 5.1% vs +0.2%, respectively) and apolipoprotein AII ( + 24.2% and +21.2% vs + 2.7%, respectively). Fenofibrate/ezetimibe and fenofibrate were equally effective in reducing TG (both ?38.3%) and in increasing HDL-C (+11.5% and + 7.9%, respectively; p = 0.282). Ezetimibe had minor effects on TG (?10.4%) and HDL-C ( + 2.2%). Among patients with low HDL-C at baseline (<1.29 mmol/L [<50 mg/dL] in women, <1.03 mmol/L [<40 mg/dL] in men), normalization of HDL-C was observed in 52.9% with fenofibrate/ezetimibe and in 58.8% with fenofibrate, compared with 20.0% with ezetimibe. Changes in hsCRP were ?25.9% with fenofibrate/ezetimibe, ?27.8% with fenofibrate, and ?10.2% with ezetimibe (not statistically significant). None of the treatments altered glucose metabolism parameters.Conclusion
In patients with type IIb dyslipidemia and features of the metabolic syndrome, coadministration of fenofibrate 145 mg and ezetimibe 10 mg daily was more effective than either monotherapy in reducing LDL-C, non-HDL-C, apolipoprotein B, and cardiovascular risk ratios, and was as effective as fenofibrate 145 mg alone in reducing TG and in increasing HDL-C in patients with low baseline HDL-C levels. 相似文献15.
《Current medical research and opinion》2013,29(9):2125-2133
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《Current medical research and opinion》2013,29(3):155-168
SUMMARYStatins and fibrates are well-established treatments for hyperlipidaemias and the prevention of vascular events. However, fibrate?+?statin therapy has been restricted following early reports of rhabdomyolysis that mainly involved gemfibrozil, originally with lovastatin, and recently, with cerivastatin. Despite this limitation, several reports describing combination therapy have been published. This review considers these studies and the relevant indications and contraindications.Statin?+?fibrate therapy should be considered if monotherapy or adding other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty acids or nicotinic acid) did not achieve lipid targets or is impractical. Combination therapy should be hospital-based and reserved for high-risk patients with a mixed hyperlipidaemia characterised by low density lipoprotein cholesterol (LDL)?>?2.6?mmol/l (100?mg/dl), high density lipoprotein cholesterol (HDL)?<?1.0?mmol/l (40?mg/dl) and/or triglycerides?>?5.6?mmol/l (500?mg/dl). These three ‘goals’ are individually mentioned in guidelines. Patients should have normal renal, liver and thyroid function tests and should not be receiving therapy with cyclosporine, protease inhibitors or drugs metabolised through cytochrome P450 (especially 3A4). Combination therapy is probably best conducted using drugs with short plasma half-lives; fibrates should be prescribed in the morning and statins at night to minimise peak dose interactions. Both drug classes should be progressively titrated from low doses. Regular (3-monthly) monitoring of liver function and creatine kinase is required.In conclusion, fibrate?+?statin therapy remains an option in high-risk patients. However, long-term studies involving safety monitoring and vascular endpoints are required to demonstrate the efficacy of this regimen. 相似文献
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《Current medical research and opinion》2013,29(10):2041-2053
ABSTRACTObjective: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.Research design and methods: Double-blind, multicenter, 6‐week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10?mg/day), the next highest (10/40 or 20?mg/day), and maximum doses (10/80 or 40?mg/day).Results: At all doses and across doses, ezetimibe/simvastatin reduced LDL‐C levels significantly more (52–61%) than rosuvastatin (46–57%; p ≤ 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p ≤ 0.005) attained LDL‐C levels < 70?mg/dL (1.8?mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (?p < 0.001), non-high-density lipoprotein cholesterol (?p < 0.001), lipid ratios (?p ≤ 0.003), and apolipoprotein B (?p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (?p = 0.004) and next highest (?p = 0.006) doses, and across all doses (?p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10?mg versus 10/20?mg/day (?p = 0.004) and 40?mg versus 10/80?mg/day (?p < 0.001).Conclusion: Ezetimibe/simvastatin was more effective than rosuvastatin in LDL‐C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies. 相似文献
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19.
Lipka LJ 《Cardiovascular drug reviews》2003,21(4):293-312
Significant numbers of patients at risk for coronary heart disease (CHD) fail to reach National Cholesterol Education Program (NCEP)-designated low density lipoprotein cholesterol (LDL-C) goals in spite of the wide range of currently available treatments, including combination therapies. Ezetimibe, the first in a class of novel cholesterol absorption inhibitors, demonstrated lipid-lowering and antiatherosclerotic activity in experimental and clinical hypercholesterolemia. Studies in hypercholesterolemic dogs showed that ezetimibe coadministered with statins caused greater lipid-lowering effects compared to either drug alone. These effects were confirmed in clinical studies of patients with primary hypercholesterolemia where initiation of treatment with ezetimibe plus a statin, or addition of ezetimibe to ongoing statin therapy, produced significant incremental reductions in LDL-C, as well as incremental increases in high-density lipoprotein cholesterol (HDL-C) and reductions in triglyceride levels. Combination therapy also significantly increased the number of patients attaining LDL-C goal at the end of treatment, compared to statin monotherapy. In studies using simvastatin, atorvastatin, pravastatin, and lovastatin, addition of ezetimibe to low dose statin was as effective as a 2- to 3-fold upward titration of the corresponding statin dose. Ezetimibe-statin combination therapy provided similar improvements in patients with primary hypercholesterolemia, as well as with heterozygous and homozygous familial hypercholesterolemia. Ezetimibe monotherapy effectively reduced plasma campesterol and sitosterol in patients with homozygous sitosterolemia. Clinical studies showed that ezetimibe was well tolerated, with a safety profile comparable to placebo when administered as monotherapy and comparable to statin alone when coadministered with a statin. These data provide strong evidence that, through their complementary lipid-lowering mechanisms, ezetimibe coadministered with a statin offers an effective combination treatment option for patients with hypercholesterolemia, including those with genetically inherited disease. 相似文献
20.
《Current medical research and opinion》2013,29(7):1951-1963
ABSTRACTBackground: Data on achieving National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals in Asia are limited.Objective: To examine treatment patterns, goal attainment, and factors influencing treatment among patients in 6 Asian countries who were taking statins.Methods: A retrospective cohort study was conducted in China, Korea, Malaysia, Singapore, Taiwan, and Thailand, where 437 physicians (41% cardiologists) recruited adults with hypercholesterolemia newly initiated on statin monotherapy.Results: Of 2622 patients meeting inclusion and exclusion criteria, approximately 66% had coronary heart disease (CHD)/diabetes mellitus, 24% had no CHD but ≥2 risk factors, and 10% had no CHD and <2 risk factors. Most patients (~90%) received statins at medium or lower equipotency doses. Across all cardiovascular risk categories, 48% of patients attained ATP III targets for low-density lipoprotein cholesterol (LDL-C), including 38% of those with CHD/diabetes (goal: <100 mg/dL), 62% of those without CHD but with ≥2 risk factors (goal: <130 mg/dL), and 81% of those without CHD and <2 risk factors (goal: <160 mg/dL). Most patients who achieved goals did so within the first 3 months. Increasing age (odds ratio (OR) = 1.015 per 1-year increment; 95% confidence interval (CI) = 1.005–1.206; p = 0.0038) and initial statin potency (OR = 2.253; 95% CI = 1.364–3.722; p = 0.0015) were directly associated with goal attainment, whereas increased cardiovascular risk (OR=0.085; 95% CI = 0.053–0.134; p < 0.0001 for CHD/diabetes mellitus at baseline compared with <2 risk factors,) and baseline LDL-C (OR = 0.990; 95% CI = 0.987–0.993); p < 0.0001 per 1-mg/dL increment) were inversely associated with LDL-C goal achievement. Limitations of this study include potential differences in treatment settings and cardiovascular risk factors between different countries and centers. In addition, the effects on cholesterol goal achievement of concomitant changes in lifestyle were not assessed.Conclusion: LDL-C goal attainment is low in Asians, particularly those with CHD/diabetes. More effective patient monitoring, treatments, including combining regimens and dose titration, and adherence to these treatments along with therapeutic lifestyle counseling may facilitate goal attainment. 相似文献