Abstract
BackgroundFew clinical studies have focused on the efficacy of lipid-lowering therapies in patients ≥65 years.MethodsAfter stabilization on atorvastatin 10 mg, hypercholesterolemic subjects ≥65 years at high/very high risk for CHD and not at LDL-C <1.81 mmol/L (with atherosclerotic vascular disease [AVD]) or <2.59 mmol/L (without AVD) were randomized to ezetimibe 10 mg plus atorvastatin 10 mg or uptitration to atorvastatin 20 mg (6 weeks) followed by uptitration to 40 mg (additional 6 weeks). A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment.ResultsAtorvastatin 10 mg plus ezetimibe produced significantly greater attainment of LDL-C, non-HDL-C, and Apo B individual and dual/triple targets vs. atorvastatin 20 mg for the entire cohort and very high-risk groups at 6 weeks. After 12 weeks, very high-risk subjects maintained significantly greater achievement of LDL-C <1.8 mmol/L (47% vs. 35%), non-HDL-C <2.6 mmol/L (63% vs. 53%) and Apo B <0.8 g/L (47% vs. 38%) single targets and dual/triple targets with atorvastatin 10 mg plus ezetimibe vs. atorvastatin 40 mg, while attainment of European target for high-risk subjects was generally similar for both treatments. Achievement of Canadian targets was significantly greater with combination therapy vs. atorvastatin 20 mg (6 weeks) or atorvastatin 40 mg (12 weeks).ConclusionsAtorvastatin 10 mg plus ezetimibe provided more effective treatment than uptitration to atorvastatin 20/40 mg for attainment of most European and Canadian guideline-recommended lipid targets in older at-risk patients.Trial registrationClinicalTrials.gov identifier NCT00418834.
Highlights
Cardiovascular disease (CVD) is a leading contributor to global morbidity and mortality, accounting for 40% of all deaths in the European Union and about one-third of all deaths in Canada (~29%) [1,2]
While the Canadian guidelines specify that treatment targets should not change based on risk assessment, the European guidelines designate different levels based on risk; more aggressive goals are recommended for patients at very high risk for CVD relative to those at high or moderate CVD risk [4]
Attainment of individual targets, dual targets of low-density lipoprotein cholesterol (LDL-C) and either non-High-density lipoprotein cholesterol (HDL-C) or Apo B, as well as the combination of all three targets was evaluated for all randomized subjects and for subgroups based on risk when evaluating targets defined in the European guidelines
Summary
Cardiovascular disease (CVD) is a leading contributor to global morbidity and mortality, accounting for 40% of all deaths in the European Union and about one-third of all deaths in Canada (~29%) [1,2]. Canadian and European guidelines have identified low-density lipoprotein cholesterol (LDL-C) as the primary therapeutic target for treatment of patients with hypercholesterolemia and CVD or CVD risk factors [3,4]. While the Canadian guidelines specify that treatment targets should not change based on risk assessment, the European guidelines designate different levels based on risk; more aggressive goals are recommended for patients at very high risk for CVD relative to those at high or moderate CVD risk [4]. There is strong justification for intensive LDL-C-lowering therapy in individuals older than 65 years with established CVD [7]. A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment
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