What is this summary about? The PLSP summarizes results from the phase 2/3 KidCOVE trial examining mRNA-1273 (Moderna's COVID-19 vaccine) in children 6 through 11 years of age. What were the results? This study reviewed results from two parts of the KidCOVE clinical trial: Part 1 of the study was performed to select a dose of mRNA-1273 (50 mu g or 100 mu g) in children. A 50-mu g dose was selected for further evaluation based on minimally unwanted side effects and sufficient antibodies (immune responses) against SARS- CoV-2. Part 2 of the study further evaluated the 50-mu g dose of mRNA- 1273 and compared it with placebo in children. Two 50-mu g doses of mRNA-1273 were well-tolerated with no new safety concerns. Two 50- mu g doses also produced antibodies (immune responses) similar to those in young adults who received mRNA1273 (100 mu g) in a separate phase 3 study ( the COVE trial). What do the results mean? Study findings suggest that two 50-mu g doses of mRNA-1273 were well-tolerated, and can prevent COVID-19 in children 6 through 11 years of age.

BACKGROUND: Elevated remnant lipoprotein cholesterol (RLP-C) levels increase cardiovascular disease risk. However, RLP-C measurement methods are not standardized, leading to variations across studies. OBJECTIVE: To evaluate the effect of ezetimibe (Eze) + statins vs statin monotherapy on RLP-C using immunoseparation (IM), vertical auto profile (VAP) ultracentrifugation, and calculated RLP-C measurement methods. METHODS: This post hoc analysis evaluated data pooled from 3 first-line (all-statin [simvastatin 10/20/40/80 mg] vs Eze + statin [Eze 10 mg + simvastatin]) and 2 second-line (statin [atorvastatin uptitrated to 40/80 mg] vs statin + Eze [atorvastatin 20/40 mg + Eze 10 mg]) studies. Similarity of RLP-C methods was evaluated using Pearson correlation coefficients and Bland-Altman plots. RLP-C changes and percent changes from baseline were measured by all 3 methods in first-line and VAP and calculated methods in second-line studies. RESULTS: Correlations between methods were generally moderate to strong for RLP-C levels, changes, and percent changes across treatment groups (r = 0.29-0.79) but with little evidence of agreement by Bland-Altman plots. Baseline RLP-C levels for Eze + statin vs all-statin groups were lower by IM (14.0 vs 14.0) compared with VAP (36.9 vs 35.9) and calculated (32.8 vs 33.3) methods. RLP-C changes (mg/dL) and percent changes from baseline were significantly greater (P<.01) with Eze + statins vs statins by VAP, calculated, and IM methods (between-treatment differences: -5.0 and -12.0, -2.0 and -5.4, and -1.5 and -12.1, respectively) in first-line, and VAP and calculated methods (between-treatment differences: -5.0 and -19.9 and -2.0 and -7.3) in second-line studies. CONCLUSION: Although the 3 methods showed little agreement, each supported Eze + statins for achieving greater RLP-C reductions vs statin monotherapy; variability of results reinforces urgent need to standardize RLP-C measurements. (C) 2019 Published by Elsevier Inc. on behalf of National Lipid Association.

Introduction: Elevated remnant-lipoprotein cholesterol (RLP-C, cholesterol mass in VLDL and IDL) increases cardiovascular disease (CVD) risk, particularly for patients with residual risk on lipid-lowering therapy (LLT). RLP-C assessment methods are not standardized and include measurement by immunoseparation (IM) and vertical auto profile ultracentrifugation (VAP [IDL+VLDL3]) or calculation (total cholesterol – HDL-C – LDL-C). This study assessed the effects of Eze, Eze + statins and statin monotherapy on RLP-C measured by these 3 methods in 1st line (statin naive/wash-out) and 2nd line (ongoing statin/uptitration) studies. Methods: RLP-C change and percent change from baseline were evaluated using pooled data from randomized 1st line (Eze vs placebo, Eze+statinsξ vs statinsξ) and 2nd line (Eze+statin‖ vs double statin¶ dose) studies. RLP-C was measured by all 3 methods for 1st line studies; VAP and calculated methods for 2nd line studies. Relationships between baseline covariates (lipids, hsCRP, age, gen...

BACKGROUND: The 2008 Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study demonstrated ezetimibe + simvastatin vs simvastatin alone had a neutral effect on the surrogate endpoint of carotid intima-media thickness. Subsequent media portrayal of the study prompted ezetimibe discontinuation in many patients.OBJECTIVE: The objective of the study was to assess the impact of ENHANCE reporting on ezetimibe discontinuation, low-density lipoprotein cholesterol (LDL-C) changes, and potential cardiovascular disease (CVD) risk.METHODS: This analysis used claims data in a retrospective, observational study of patients receiving ezetimibe + statin and compared LDL-C for patients who discontinued ezetimibe (n = 970) vs those who continued ezetimibe + statins (n = 3706) after ENHANCE results disclosure. Change in relative CVD risk was estimated from the absolute LDL-C difference between groups per the Cholesterol Treatment Trialists' meta-analysis of statin trials.RESULTS: The rate of ezetimibe discontinuation was 2% in the 6 months before and 21% in the 6 months after reporting of ENHANCE results. Among patients who ultimately discontinued vs continued ezetimibe, respective mean LDL-C levels were 79.8 and 78.3 mg/dL 6 months before reporting of the ENHANCE results and 93.5 and 78.1 mg/dL 6 months after reporting of ENHANCE. Predictive application of the Cholesterol Treatment Trialists' meta-analysis suggested the 13.9 mg/dL increase in mean LDL-C translated to a 9.4% increase in relative CVD risk for those who discontinued ezetimibe.CONCLUSION: After reporting of the neutral ENHANCE results, ezetimibe discontinuation rate increased, LDL-C levels increased, and predicted CVD risk increased among those who discontinued ezetimibe. Characterization of clinical outcomes regarding lipid-altering agents based on surrogate biomarker studies not designed to assess CVD outcomes may be misleading, potentially placing patients at increased CVD risk. (C) 2017 National Lipid Association. All rights reserved.

Background and aims: Familial hypercholesterolemia (FH) is a life-threatening disease, characterized by elevated LDL-C levels and a premature, increased risk of coronary heart disease (CHD) that is globally underdiagnosed. The percentage of patients with possible or probable FH in various countries was examined in the Dyslipidemia International Study (DYSIS).Methods: DYSIS is a multinational, cross-sectional observational study of 54,811 adult outpatients treated with statin therapy. The percentages of patients with high levels of LDL-C, and with possible or probable FH, were assessed using the Dutch scoring method for FH across 29 countries, in age subgroups for the analysis population and among diabetes patients.Results: Despite statin therapy, 16.1% (range 4.4-27.6%) of patients had LDL-C > 3.6 mmol/L (140 mg/dL) across countries and the prevalence of possible FH was 15.0% (range 5.5-27.8%) and 1.1% (range 0.0-5.4%) for probable FH. The highest percentages of probable FH occurred in Egypt (5.4%), the Baltic states (4.2%), Russia (3.2%), and Slovenia (3.1%), with the lowest rates in Israel (0.0%), Canada (0.2%), and Sweden (0.3%). Rates of FH were the highest in younger patients (45-54 years) for secondary prevention, regardless of the presence/absence of diabetes.Conclusions: Despite statin therapy, high LDL-C levels and rates of possible and probable FH were observed in some countries. The prevalence of FH was the highest in younger age patients, and > 60% of patients with probable FH displayed CHD. Earlier diagnosis and treatment of patients with FH are needed to reduce CHD risk in these patients. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy.

In numerous clinical trials, lowering LDL-C with statin therapy has been demonstrated to reduce the risk of cardiovascular disease (CVD) in primary and secondary prevention settings. Guidelines recommend statins for first-line therapy in cholesterol-lowering management of patients with CVD risk. Despite increased statin monotherapy use over the last decade, a number of patients with high CVD risk do not achieve optimal LDL-C lowering. Guidelines recommend consideration of statin combination therapy with nonstatin agents for these patients. However, combination therapy approaches have been hampered by neutral findings. Recently, ezetimibe added to simvastatin therapy reduced cardiovascular events in acute coronary syndrome patients, more than simvastatin alone. This article provides an overview of various agents in combination with statin therapy on cardiovascular outcomes. Other lipid-lowering agents in development, including PCSK9 and CETP inhibitors in development, are also described.

This brief article provides complementary data supporting the results reported in “Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006” [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988–2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of lipid-lowering therapy and control of LDL-C that may have impacted the variability in the results of cIMT studies.

Objectives: The ACC/AHA 2013 cholesterol guidelines specify treatment of patients classified by cardiovascular risk to achieve LDL-C reductions of ≥50% and ≥30 with high- and moderate-intensity statin therapies, respectively. The LDL-C-lowering responses to statin and ezetimibe+statin therapies for these parameters were evaluated in statin-naïve, hypercholesterolemic patients.

Objectives: Changes in cIMT have not been consistently correlated with cardiovascular risk reduction in clinical studies. The variability of carotid intima media thickness (cIMT) changes in published statin LDLC-lowering studies in relation to various baseline and study characteristics was assessed.Methods: This was an exploratory analysis of study-level data pooled from statin-treatment arms of 13 studies conducted during 1988-2006. Baseline mean common carotid artery (CCA)/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Potential relationships between pre-specified covariates and cIMT changes were assessed.Results: Baseline mean CCA/cIMT and LDL-C levels were higher in the combined studies conducted before year 2000 (0.8521 mm) than after 2000 (0.7458 mm), and somewhat higher in study populations of patients with coronary heart disease risk and those with greater LDL-C reductions. Mean CCA/cIMT changes were also larger for the studies conducted before 2000 (-0.0119 mm/year) than after 2000 (-0.0013 mm/year). Notably, studies conducted before 2000 were of longer duration (-2 years) than after 2000 (<2 years). Heterogeneity in cIMT change was attributed to baseline and study-design characteristics. Longer study duration and greater LDL-C reductions were significantly related to larger annualized cIMT changes. Maximum cIMT results were similar.Conclusion: Baseline cIMT and LDL-C levels were lower, and cIMT changes were smaller in statin cIMT trials conducted after 2000 than those before 2000. These trends are consistent with increased treatment and control of high LDL-C levels over recent years in clinical practice, and may influence the results of cIMT studies. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:Little is known regarding relationships between high-sensitivity C-reactive protein (hsCRP) and lipoproteins other than low-density lipoprotein cholesterol (LDL-C). High-density lipoprotein (HDL), with both anti-inflammatory and cholesterol-mediating effects, is of particular interest. This exploratory analysis assessed associations between hsCRP and lipids in older (>65 years) patients with moderate and/or high cardiovascular disease risk, before and after treatment with ezetimibe/simvastatin (E/S) or atorvastatin (ATV).METHODS:An analysis of a multicenter, randomized, double-blind, 12-week study. Correlations were assessed in 1054 patients with both baseline and 12-week hsCRP ≤ 10 mg/L, pooled across doses of E/S (10/20 and 10/40 mg) and ATV (10, 20, and 40 mg), and combined E/S + ATV treatments. Because of multiple comparisons, observed relationships were considered significant only if P values were < .01.RESULTS:Correlations between baseline levels of hsCRP and either LDL-C, non-HDL-C, or apolipoprotein B were weak and nonsignificant in the E/S, ATV, and E/S + ATV groups. After 12 weeks of treatment, these correlations increased slightly and significantly in all groups, except for LDL-C in the ATV group. HDL-C was significantly but inversely correlated with hsCRP in the ATV and E/S + ATV groups at baseline, and in all groups at 12 weeks. Only with HDL-C did change correlate with change in hsCRP in both the E/S and combined groups.CONCLUSIONS:Relationships between hsCRP and lipid factors in older patients were weak at baseline and somewhat stronger after treatment. HDL-C was inversely and consistently correlated with baseline and 12-week on-treatment hsCRP and with therapy-induced changes in HDL-C and hsCRP.

Elevated remnant-lipoprotein cholesterol (RLP-C) levels increase the risk of ischemic heart disease (IHD). The concurrence of RLP-C assessment by different separation methods is not well described. This analysis examined RLP-C assessed by immunoseparation (IM) and vertical auto profile (VAP [IDL+

Objective: The recently published ACC/AHA 2013 cholesterol guidelines do not specify lipid target levels, but rather treatment of patients classified by cardiovascular risk to achieve LDL-C reductions of ≥50% and ≥30 - <50% with high and moderate intensity statin therapy respectively. This analysis evaluated the variability of treatment responses to statin therapy for these parameters in statin-naïve patients with hypercholesterolemia (HC). Methods: Data pooled from 14 randomized, controlled, double-blind clinical trials in HC patients were categorized per the 4 risk groups specified by ACC/AHA 2013 guidelines: 1) atherosclerotic cardiovascular disease (ASCVD), 2) baseline LDL-C >190 mg/dL, 3) diabetes (DM) and 4) 10 year ASCVD risk ≥7.5% (no ASCVD or DM). Mean % change from baseline in LDL-C, the percentage of patients who attained LDL-C reductions of ≥50% and ≥30 - <50% and variability of LDL-C lowering responses on recommended therapy among risk groups were assessed. Results: Mean % LDL-C changes from baseline ranged from -49.5 to -52.2% and -37.7 to -40.5% on high and moderate intensity statins, respectively across risk groups (Figure). The percentages of patients who achieved LDL-C reductions of ≥50% on high intensity statins were 62 - 70%, and who attained reductions ≥30 - <50% were 52 - 60% (77 - 89% for ≥30%) on moderate intensity therapy. The variability of % changes from baseline in LDL-C (SE = 0.7 to 2.1) and proportions of patients who achieved target LDL-C reductions were generally similar across risk groups for high and medium intensity statins. Conclusion: In this analysis, only 2/3 of patients achieved LDL-C reductions ≥50% on high intensity statins and ~80% of patients attained reductions ≥30% on moderate statin therapy. These results highlight the importance of assessing the response of patients to cholesterol lowering therapy when following the AHA/ACC guidelines and consideration of alternatives for those patients in need of greater LDL-C lowering.

Co‐administration of ezetimibe with atorvastatin is a generally well‐tolerated treatment option that reduces LDL ‐C levels and improves other lipids with greater efficacy than doubling the atorvastatin dose. The objective of the study was to demonstrate the equivalent lipid‐modifying efficacy of fixed‐dose combination ( FDC ) ezetimibe/atorvastatin compared with the component agents co‐administered individually in support of regulatory filing. Two randomized, 6‐week, double‐blind cross‐over trials compared the lipid‐modifying efficacy of ezetimibe/atorvastatin 10/20 mg ( n = 353) or 10/40 mg ( n = 280) vs. separate co‐administration of ezetimibe 10 mg plus atorvastatin 20 mg ( n = 346) or 40 mg ( n = 280), respectively, in hypercholesterolemic patients. Percent changes from baseline in LDL ‐C (primary endpoint) and other lipids (secondary endpoints) were assessed by analysis of covariance; triglycerides were evaluated by longitudinal‐data analysis. Expected differences between FDC and the corresponding co‐administered doses were predicted from a dose–response relationship model; sample size was estimated given the expected difference and equivalence margins (±4%). LDL ‐C‐lowering equivalence was based on 97.5% expanded confidence intervals ( CI ) for the difference contained within the margins; equivalence margins for other lipids were not prespecified. Ezetimibe/atorvastatin FDC 10/20 mg was equivalent to co‐administered ezetimibe+atorvastatin 20 mg in reducing LDL ‐C levels (54.0% vs. 53.8%) as was FDC 10/40 mg and ezetimibe+atorvastatin 40 mg (58.9% vs. 58.7%), as predicted by the model. Changes in other lipids were consistent with equivalence (97.5% expanded CI s <±3%, included 0); triglyceride changes varied more. All treatments were generally well tolerated. Hypercholesterolemic patients administered ezetimibe/atorvastatin 10/20 and 10/40 mg FDC had equivalent LDL ‐C lowering. This FDC formulation proved to be an efficacious and generally well‐tolerated lipid‐lowering therapy.

OBJECTIVE:We compared the variability of LDL-C-lowering responses to treatment with ezetimibe + statins versus statins in hypercholesterolemic patients. METHODS:An analysis of patient-level data pooled from 27 double-blind, placebo and/or active-controlled studies in 21,671 patients treated with ezetimibe + statins versus statins on first-line (statin-naïve/wash-out) or second-line (on statin, randomized to ezetimibe versus placebo [add-on] or ezetimibe versus uptitrated statin [uptitrate]) for 6-24 wks. Variances (standard deviation [SD], coefficient of variation [CV], and root mean squared error [RMSE] adjusted for various factors) for % change from baseline in LDL-C were compared. RESULTS:In first-line and second-line add-on studies, the variability (SD, RMSE) of % change from baseline in LDL-C was lower in ezetimibe + statin-treated patients versus statin-treated patients, ±covariates. Differences were small but statistically significant due to the large sample size. In second-line uptitrate studies, ezetimibe + statin treatment resulted in greater unadjusted variability (SD) versus statin therapy, while the adjusted variability (RMSE) was significantly lower. Relative variability (CV=SD/mean) was lower for ezetimibe + statins versus statin therapy for all study types, being more pronounced in second-line add-on and uptitrate studies, attributed to larger mean LDL-C reductions for ezetimibe + statins versus statin groups. When assessed by individual study/type, statin brand, potency or dose, the CVs remained lower for ezetimibe + statins versus statins in second-line studies. The SDs showed no consistent trend for either therapy. CONCLUSION:In hypercholesterolemic patients, the absolute variability of LDL-C-lowering responses to ezetimibe + statins was not greater versus statins alone and appeared lower when adjusted for other factors. Relative variability was lower in patients treated with statins + ezetimibe. A better understanding of the variability of the LDL-C lowering response may help guide clinicians in making therapeutic decisions.

Goal attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) is suboptimal. Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We examined physicians’ treatment recommendations in high-risk patients whose LDL-C remained uncontrolled despite statin monotherapy.

Background Patients with diabetes mellitus and cardiovascular disease may not achieve adequate low‐density lipoprotein cholesterol (LDL‐C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL‐C–lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL‐C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose‐doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low‐ and high‐density lipoprotein particle number and lipoprotein‐associated phospholipase A2 [Lp‐PLA2]) was assessed. Methods and Results Treatment effects on low‐ and high‐density lipoprotein particle number (by NMR) and Lp‐PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low‐density lipoprotein‐particle number numerically more than did statin dose‐doubling and was comparable with R10 (−133.3, −94.4, and −56.3 nmol/L, respectively; P>0.05). Increases in high‐density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose‐doubling (1.5 and −0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low‐density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose‐doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp‐PLA2 activity significantly more than did statin dose‐doubling (−28.0 versus −3.8 nmol/min per mL, P<0.05) and was comparable with R10 (−28.0 versus −18.6 nmol/min per mL; P>0.05); effects on Lp‐PLA2 concentration were modest. Conclusions In diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp‐PLA2 activity more than did statin dose‐doubling and was comparable with R10, consistent with its lipid effects. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

Dr. Toth has served on the speakers bureau for Abbvie, Amarin, AstraZeneca, Merck, Kowa, and is a consultant to Amgen, AstraZeneca, Genzyme, Kowa, and Merck. None

BACKGROUND: Statin combination therapy and statin uptitration have been shown to be efficacious in low-density lipoprotein cholesterol (LDL-C) lowering and are recommended for patients with highrisk coronary heart disease (CHD) who do not reach guideline-endorsed LDL-C goals on statin monotherapy.OBJECTIVE: This analysis evaluated treatment practice patterns and LDL-C lowering for patients with CHD/CHD risk equivalent on statin monotherapy in a real-world practice setting in the United States.METHODS: In this retrospective, observational study, patients with CHD/CHD risk equivalent on statin therapy were identified during 2004 to 2008 in a US managed care database. Prescribing patterns and effect of switching from statin monotherapy to combination ezetimibe/simvastatin therapy vs uptitration to higher statin dose/potency level and no change from initial statin potency on LDL-C lowering were assessed. Percentage of change from baseline in LDL-C levels and odds ratios for LDL-C goal attainment were estimated with analyses of covariance and logistic regression.RESULTS: Of 27,919 eligible patients on statin therapy, 2671 (9.6%) switched to ezetimibe/ simvastatin therapy, 11,035 (39.5%) uptitrated statins, and 14,213 (50.9%) remained on the same statin monotherapy. LDL-C reduction from baseline and attainment of LDL-C <100 and <70 mg/dL were substantially greater for patients who switched to ezetimibe/simvastatin therapy (-24.0%, 81.2%, and 35.2%, respectively) than for patients who titrated (-9.6%, 68.0%, and 18.4%, respectively) or remained on initial statin therapy (4.9%, 72.2%, and 23.7%, respectively). The odds ratios for attainment of LDL-C <100 and <70 mg/dL were also higher for patients who switched than for patients who uptitrated and had no therapy change than for patients who titrated vs no therapy change. Similarly, among a subgroup of patients not at LDL-C <100 mg/dL on baseline therapy, attainment of LDL-C <100 and <70 mg/dL was greater for patients who switched than for statin uptitration vs no change, as well as for patients who uptritrated statins vs no therapy change.CONCLUSION: In this study, LDL-C lowering and goal attainment rates improved substantially for patients with high-risk CHD on statin monotherapy who switched to combination ezetimibe/statin or uptitrated their statin therapies; however, approximately one-third of these patients still did not attain the optional recommended LDL-C goal of <70 mg/dL. Moreover, these higher efficacy lipid-lowering therapies were infrequently prescribed, indicating the need for further assessment of barriers to LDL-C goal attainment in actual practice settings. (c) 2014 National Lipid Association. All rights reserved.