The ezetimibe controversy - can this be resolved by comparing the clinical trials with simvastatin and ezetimibe alone and together?
ABSTRACT INTRODUCTION: The primary target in the treatment of hypercholesterolemia is often to lower low-density lipoprotein (LDL) cholesterol, rather than improve clinical outcomes. Despite the wide use of lipid-modifying drugs, considerable cardiovascular mortality and morbidity remains with this disease. Hypercholesterolemia plays a key role in the development and progression of atherosclerosis and can lead to cardiac heart disease. AREAS COVERED: The purpose of this review is to determine whether ezetimibe has proven clinical benefits; it discusses the clinical trials of simvastatin and ezetimibe alone and in combination. EXPERT OPINION: Simvastatin has been clearly shown to decrease LDL-cholesterol, which is associated with the slowing of atherosclerosis and a reduction in cardiovascular morbidity and mortality. Ezetimibe alone or in the presence of simvastatin lowers LDL-cholesterol. However, ezetimibe alone or in the presence of simvastatin has not been shown to have any irrefutable beneficial effects on atherosclerosis or cardiovascular morbidity and mortality. Thus, until/unless the use of ezetimibe is clearly shown to improve clinical outcomes, its use should be largely restricted to clinical trials investigating clinical outcomes and should not be used routinely in everyday practice.
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ABSTRACT: Abstract Background. We aimed to describe the contemporary management of patients with systolic chronic heart failure (CHF) during a cardiac rehabilitation (CR) stay and present outcomes with focus on lipids, blood pressure, exercise capacity, and clinical events. Methods. Comparison of 3,199 patients with moderately or severely impaired left ventricular ejection fraction (low EF, 13.3%) and 20,913 patients with slightly reduced or normal LVEF (normal EF, 86.7%) who underwent an inpatient CR period of about 3 weeks in 2009-2010. Results. Patients with low EF were somewhat older (65.1 vs. 63.0 years, p< 0.0001), had more often risk factors such as diabetes mellitus (39.7% vs. 32.0%, p< 0.0001) or other comorbidities. The overall rate of patients with regular physical activity of at least 90 minutes per week prior to CR was low overall (54.4%), and reduced in patients with low EF compared to those with normal EF (47.7% vs. 55.5%, p< 0.0001). The rate of patients that achieved lower LDL cholesterol (< 100 mg/dl), total cholesterol (< 200 mg/dl) and triglyceride (< 150 mg/dl) values at discharge increased compared to baseline. Mean blood pressure was substantially lower in the low EF group compared to the normal EF group both at baseline (124/75 vs. 130/78 mmHg, p< 0.0001) and at discharge (119/72 vs. 124/74 mmHg, p< 0.0001). Maximum exercise improved substantially in both groups (at baseline 71 vs 91 Watts, p < 0.0001; at discharge 85 vs 105 Watts, p< 0.0001). Event rates during CR were low and only 0.3% in the low EF group died. As limitations to this study, information on BNP, NT-pro BNP and/or cardiac troponin were not documented, and no long-term information was collected beyond the 3-week CR stay. Conclusions. Patients with CHF account for a considerable proportion of patients in CR. Also patients with moderate/severe EF benefited from the participation in CR, as their lipid profile, and physical fitness improved.Current Medical Research and Opinion 10/2014; 31(2):1-23. DOI:10.1185/03007995.2014.977854 · 2.37 Impact Factor
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ABSTRACT: Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 55 is January 06, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.Annual Review of Pharmacology 08/2014; 55(1). DOI:10.1146/annurev-pharmtox-010814-124614 · 18.52 Impact Factor
Article: [Lipid therapy in daily routine].[Show abstract] [Hide abstract]
ABSTRACT: Patients with increased cardiovascular risk profile are frequently seen in general practice. Comprehensive management of modifiable risk factors, in particular dyslipidemia, is mandatory. Many studies in clinical practice have shown a gap between the recommendations in clinical guidelines and the actual situation. Current data on the management situation of patients with high cardiovascular risk is provided by the prospective registry LIMA. Primary care physicians in 2,387 offices throughout Germany documented 13,924 patients with coronary artery disease (CAD), diabetes mellitus or peripheral arterial disease (PAD). Treatment with simvastatin 40 mg was an inclusion criterion. Physicians documented drug utilization, laboratory values (lipids, blood glucose), blood pressure and clinical events over one year and received feedback about the target value attainment of their patients after data entry. Mean age of the patients was 65.7 years, and 61.6 % were men. CAD was reported in 70.6 %, diabetes mellitus in 58.2 % and PAD in 14.9 %. Most patients (68 %) received simvastatin as monotherapy also after the inclusion visit; 20.6 % of patients received in addition the cholesterol absorption inhibitor (ezetimibe) in the first 6 months, and 23.3 % in the second 6 months. Patients achieved the LDL-cholesterol target value in 31.8 % at entry and 50.0 % after one year. The blood pressure target < 140 /90 mmHg was reached by 65.8 % after one year. Of patients with diabetes mellitus 40.0 % reached an HbA1c value below 6.5 %. Clinical events (death, hospitalization, (cardio-) vascular events, and dialysis) were reported by 11.7 % of patients between entry and Month 6, and by 12.0 % between Month 7 and 12. In daily practice comprehensive management of risk factors in patients at high cardiovascular risk remains a challenge. For normalization of increased LDL cholesterol values addition of ezetimibe to existing statin therapy improves the chances of patients for target level attainment.DMW - Deutsche Medizinische Wochenschrift 10/2012; 137(40):2047-52. DOI:10.1055/s-0032-1327203 · 0.55 Impact Factor