Clinical experience with ezetimibe/simvastatin in a Mediterranean population

ABSTRACT

Objectives: This study aimed to describe the clinical experience of the ezetimibe (EZE)/simvastatin (SIMVA) combination in a hypercholesterolaemic Greek population who did not attain the cholesterol goals on statin treatment alone.

Methods: Patients already treated with a statin, at any dose, for at least 8 weeks, with LDL-C levels above the goal, (>100, >130 or >160?mg/dl according to their risk category), where the physician chose EZE/SIMVA as appropriate treatment, entered the study. Medical history, demographics and laboratory values were recorded at baseline and 2 months later.

Results: The study included 1514 patients (male 53.4%) of mean age 60.1?±?10.5 years. Diabetes mellitus was reported in 29.9% of the patients, 61.2% had hypertension, 39% were obese, 10.5% had a history of myocardial infarction and 6.8% had a history of stroke or peripheral arterial disease. Current and ex-smoking was reported in 46.8%. Atorvastatin (33%) and SIMVA (27.2%) were the most frequently used statins prior to using the EZE/SIMVA regimen. After 2 months of EZE/SIMVA therapy mean LDL-C was reduced by 33%, mean total cholesterol by 26%, mean triglycerides by 15%, while HDL-C was increased by 10%. The percentage of patients who achieved the LDL-C goal with EZE/SIMVA was 73.8%. One serious adverse event, not related to study treatment and 23 adverse events in total were recorded. There was a significant decrease in serum creatinine levels in patients with baseline values greater than 1.0?mg/dl (88?μmol/L).

Conclusions: Treatment with the EZE/SIMVA combination appears an effective and safe therapeutic option for patients who do not achieve the LDL-C goals on statin therapy alone.     

Sustained effects in hypercholesterolaemic patients on combined simvastatin/ezetimibe treatment: observational cohort study in clinical practice

ABSTRACT

Background: In order to reduce individual cardiovascular risk, many patients require life-long lipid-lowering therapy, often as a drug combination approach. We aimed to describe the usage pattern, effectiveness and tolerability of long-term treatment with lipid-lowering agents, with particular focus on an oral combination of simvastatin (SIM 10, 20, 40 or 80?mg) plus ezetimibe (EZ 10?mg).

Methods: A prospective, observational study in 512 general practices throughout Germany. From a sample of patients at moderate or high cardiovascular risk who had previously taken part in a half-year study of an SIM/EZ combination, 5485 patients were documented after 1 year of treatment (mean 58?±?16 weeks) with regard to lipid parameters, adverse drug reactions (ADRs) and adverse events.

Results: At the start of follow-up, 78.6% of patients were still on the SIM/EZ combination. At the end of follow-up, mean low density lipoprotein cholesterol (LDL-C) in patients on the combination versus those on other lipid-lowering therapy was reduced by 29.3 vs. 17.6% compared with baseline, total cholesterol by 23.1 vs. 14.5%, mean high density lipoprotein cholesterol (HDL-C) was increased by 15.9 vs. 13.4%, and mean triglycerides were reduced by 16.1 vs. 7.9%. Individual LDL-C targets were achieved by 56.6% on the SIM/EZ combination versus 35.9% on other therapy. In the long term (but not the short term), low acceptance of nutrition counselling as rated by the physician was associated with poor lipid levels. ADRs during follow-up occurred in 18 patients (0.3%; all cases non-serious), with seven cases of myalgia, and three cases each of nausea or arthralgia.

Conclusions: This observational study showed that long-term therapy with the SIM/EZ combination resulted in sustained beneficial effects on serum lipids and was well-tolerated. Compared to patients with therapy discontinuations or switches, those remaining on the combination had better outcomes regarding lipid status.     

Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease

ABSTRACT

Objective: 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.     

辛伐他汀联合丹参注射液治疗冠心病合并糖尿病的疗效观察

目的 探讨辛伐他汀联合丹参注射液治疗冠心病合并糖尿病的临床疗效.方法 将114例冠心病合并糖尿病患者随机分为两组,对照组57例采用常规治疗,加用辛伐他汀,观察组57例则在对照组的基础上加用丹参注射液,两组连续治疗3个月,比较两组心功能改善、心绞痛发作、血清超氧化物歧化酶(SOD)、丙二醛(MDA)和空腹血糖含量以及不良...     

辛伐他汀治疗糖尿病合并冠心病的疗效观察

目的 观察辛伐他汀治疗糖尿病合并冠心病的临床疗效.方法 选择47例糖尿病合并冠心病患者,均给予口服辛伐他汀20mg/次,1天1次,连续治疗12周,治疗前后均检测患者血糖、血脂、血浆一氧化氮(NO)与内皮索(ET)水平以及血清定粉样蛋白A(A-SAA),并测定血管内皮细胞的功能.结果 47例患者经过12周的治疗,血脂和肱...     

Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe

ABSTRACT

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.     

冠心病合并2型糖尿病患者临床和冠脉造影特点分析

目的 探讨冠心病(CHD)合并2型糖尿病(DM)患者的临床和冠脉造影特点.方法 选择经冠脉造影证实的冠心病患者515例,根据是否合并糖尿病将其分为糖尿病组(353例)和非糖尿病组(162例),比较两组患者的临床和冠脉造影资料.结果 合并2型糖尿病的冠心病患者发生高血压和急性心肌梗死的比例明显高于非糖尿病的冠心病患者(P＜0.01),前者血甘油三酯水平也明显高于后者(P＜0.01).冠心病合并2型糖尿病患者多发生多支病变,左主干病变也明显高于非糖尿病者(P＜0.01).结论 冠心病合并2型糖尿病患者临床和冠脉病变复杂.     

Predictors of uncontrolled hyperlipidaemia in high-risk ambulatory patients in primary care

ABSTRACT

Objective: 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 HbA_1c, 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.     

60例伴有糖尿病的冠心病心律失常分析

目的探讨伴有糖尿病的冠心病患者心律失常倾向。方法对60例伴有糖尿病(DM)的冠心病患者(A组)与60例非糖尿病冠心病患者(B组)临床资料进行回顾性对照分析。结果A组的心律失常发生率显著高于B组(P＜0．05)；同时，左心衰竭、感染和低血糖等并发症在A组患者中较多；A组患者的死亡率明显高于B组(P＜0．05)。结论早期发现并积极预防糖尿病，重视DM冠心病患者的高并发症倾向特别是心律失常，并采取必要措施，对改善患者生存质量、降低死亡率可能具有重要意义。     

糖尿病合并冠心病患者介入治疗后的护理

目的:探讨糖尿病(diabetes mellitus,DM)合并冠心病患者介入治疗后的观察及护理.方法:回顾性分析我院DM合并冠心病患者48例介入治疗的临床资料,明确DM合并冠心病患者介入治疗后的护理要点.结果:48例DM合并冠心病患者介入治疗(percutaneous coronary intervention,PCI)后发现心理问题41例,腰酸背痛23例,排尿困难16例,伤口渗血17例,血压下降4例,急性心衰3例,心律失常5例,心肌梗死1例.结论:血糖、心率、血压的监测,相对有效的护理,出院指导等是此类患者护理的要点,对于提高患者PCI的成功率及患者的长期生存均非常重要.     

30例糖尿病合并冠心病患者的心率变异性分析

目的：研究2型糖尿病（DM）合并冠心病（CHD）与单纯2型DM对心率变异性（HRV）的影响，方法：对66例2型DM患者，其中30例合并CHD，36例为单纯2型DM，进行24h HEV时域及频域分析，同时与年龄，性别相当的20例健康成年人HRV资料比较。结果：（1）2型DM患者各时域及频域分析指标均较正常组降低（P＜0．05或P＜0．01），但VLF和LF／HF增高（P＜0．05或P＜0．01），（2）与单纯2型DM患者比较，有CHD合并症的2型DM患者，HRV各参数也明显降低（P＜0．05，P＜0．01），但VLF和LF／HF增高（P＜0．05），结论：2型DM患者存在着HRV异常，其异常程度与病变轻重成正比，合并CHD者异常更显著，提示2型DM患者的HRV分析有助于预测恶性心血管疾病的发生。     

冠心病合并2型糖尿病患者冠状动脉造影分析

目的探讨冠心病（CHD）合并2型糖尿病（T2DM）患者的冠状动脉造影特点。方法选择经冠状动脉造影证实的冠心病292例,分为合并2型糖尿病组（糖尿病组）141例和冠心病非糖尿病组（对照组）151例,对冠脉造影结果进行比较。结果与非糖尿病组比较,血管狭窄的程度较重（狭窄程度I〉75％的比例为78．01％比52．32％（P〈0．05）,3支血管均发生病变的比例显著增高（59．57％比36．42％,P〈0．05）。结论合并2型糖尿病患者与非糖尿病患者的冠状动脉造影表现的差异有统计学意义,冠心病合并2型糖尿病患者冠脉病变广泛且程度较重。     

2型糖尿病合并冠状动脉粥样硬化性心脏病冠状动脉病变特点

目的研究2型糖尿病(T2DM)合并冠心病患者冠状动脉病变的特点。方法回顾性分析经冠状动脉造影诊断的75例2型糖尿病合并冠心病患者(糖尿病组)和68例不伴有2型糖尿病的冠心病患者(对照组)的体重指数、血压及血脂等指标,比较两组冠状动脉病变特点。结果与未合并糖尿病的冠心病组相比,合并糖尿病的冠心病组存在有更明显的血压、血脂异常等心血管危险因素。冠状动脉造影结果显示,糖尿病合并冠心病时多为多支病变,并发冠状动脉血管三支以上病变发生率高,且血管狭窄程度重,左主干受累程度比例高。结论2型糖尿病合并冠心病时,血脂异常明显,冠状动脉病变较未合并糖尿病冠状动脉病变更严重。     

冠心病合并2型糖尿病患者的脂代谢和冠状动脉造影分析

目的探讨冠状动脉粥样硬化性心脏病（冠心病）合并2型糖尿病患者的脂代谢和冠状动脉造影特点。方法选择经冠状动脉造影证实的冠心病患者310例,其中合并糖尿病患者106例,不合并糖尿病患者204例。比较2类患者的临床和冠状动脉造影资料。结果合并糖尿病的冠心病患者的TG、LDL—C水平较不合并糖尿病者明显升高,HDL—C水平明显下降[合并糖尿病者TG、LDL-C、HDL-C水平分别为（2．86±0．61）mmol／L、（3．42±0．53）mmol／L、（1．05±0．12）mmol／L;不合并者分别为（1．80±0．41）mmol／L、（2．74±0．21）mmol／L、（1．75±0．13）mmol／L],差异有统计学意义（P〈0．05）。合并糖尿病的患者中,血脂异常者冠状动脉主要分支病变均增多。结论冠心病合并2型糖尿病患者的脂代谢明显紊乱,冠状动脉病变较为复杂。     

曲美他嗪对老年冠心病合并糖尿病患者心脏舒张功能的影响简

目的探讨曲美他嗪对老年冠心病合并糖尿病患者心脏舒张功能的影响。方法将126例舒张功能不全的老年冠心病合并糖尿病患者,随机分成常规口服药物组60例（对照组）和曲美他嗪组66例（治疗组）。2组患者均给予降糖、冠心病二级预防用药,治疗组在运用上述药物治疗的基础上加用曲关他嗪口服,每次20mg,每日3次。治疗3个月观察患者血糖水平及超声心动图指标的变化。结果治疗组治疗后心脏舒张功能、左心室射血分数与治疗前相比较均有改善,差异有统计学意义（P〈0．01）;而对照组治疗前后心脏舒张功能、左心室射血分数差异无统计学意义（P〉0．05）;2组治疗后比较差异有统计学意义（P〈0．01）。结论曲美他嗪能改善老年冠心病合并糖尿病患者的心脏舒张功能及收缩功能,并且安全性较好。     

冠心病合并糖尿病者冠脉造影结果分析

目的 通过冠脉造影探讨冠心病合并糖尿病者冠脉病变特点。方法 回顾我院2000—2006年1068例冠心病患者造影检查阳性者对380例糖尿病合并冠心病者行冠脉造影，并与688例非糖尿病的冠心病患者相比较。结果 糖尿病并冠心病者三支病变和弥漫性病变者分别为56．8％和58％，明显高于非糖尿病者（21.5％和16％）。结论 冠心病并糖尿病者冠脉造影主要表现为多支病变及复杂病变，而非糖尿病者多为单支或双支病变，糖尿病组冠脉狭窄程度明显高于非糖尿病组，显示糖尿病对冠脉病变影响大，糖尿病为冠心病的独立危险因素。     

冠心病并发2型糖尿病患者的冠状动脉病变特点

目的　探讨冠心病并发 2型糖尿病患者的冠状动脉病变及其临床特点。方法　回顾分析冠心病并发 2型糖尿病患者 ( 4 0例 )和冠心病不并发 2型糖尿病患者 ( 2 5 2例 )冠脉造影特点并结合临床特点加以对照研究。结果　冠心病并发 2型糖尿病患者 3支病变及弥漫性病变多见。该组患者倾向于积聚多种心血管危险因素 (高血压、血脂异常 ) ,无痛性心肌缺血较多 ,住院期间并死率较高。结论　冠心病并发 2型糖尿病患者冠脉病变严重 ,糖尿病早期诊断对冠心病预后非常重要。     

辛伐他汀对冠心病合并高血压患者尿蛋白的影响

目的探讨辛伐他汀对冠心病合并高血压患者尿蛋白的影响。方法选取内蒙古自治区人民医院2008年4月至2011年1月收治冠心病合并高血压患者110例,采用随机数字表法分为对照组和辛伐他汀组,每组各55例;分别给予安慰剂和辛伐他汀40mg／d,疗程均为6个月;比较两组患者治疗前后TG（甘油三酯）、TC（总胆固醇）、HDL—C（高密度脂蛋白）、LDL—C（低密度脂蛋白）、血肌酐（Cr）、24h尿微量白蛋白（UMA）、血清超敏C反应蛋白（hsCRP）及血压水平等。结果两组患者治疗前TG、TC、HDL—C、LDL～C、Cr、UMA及hsCRP水平组间比较无显著差异（P〉0．05）;治疗后两组患者TG、TC、HDL—C、LDL—C、Cr、UMA及hsCRP水平较治疗前均明显改善,且辛伐他汀组患者治疗后TG、TC、HDL—C、LDL—C、Cr、UMA及hsCRP水平明显优于对照组（P〈0．05）;同时两组患者治疗前后收缩压、舒张压水平比较差异无统计学意义（P〉0．05）。结论辛伐他汀能够有效改善冠心病合并高血压患者尿蛋白水平,可用于早期肾病临床治疗。