Greater Reductions In Low-density Lipoprotein Cholesterol Research Articles

Effects of age, gender and statin dose on lipid levels: Results from the VOYAGER meta-analysis database

Background and aimsThe effectiveness of statins in the treatment of dyslipidaemia and reduction of cardiovascular risk is well established. However, the association of statin-mediated lipid effects with age and gender is unclear. This study aimed to determine whether age and gender are associated with statin-mediated changes in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL-C. MethodsIndividual patient data (n = 32,258) were obtained from VOYAGER. Least-squares mean percentage change from baseline in LDL-C, non-HDL-C and HDL-C with atorvastatin 10–80 mg, rosuvastatin 5–40 mg or simvastatin 10–80 mg was estimated in women aged <70 years, women aged ≥70 years, men aged <70 years and men aged ≥70 years. ResultsAll statins and doses gave significant dose-dependent reductions in LDL-C and non-HDL-C, and increases in HDL-C, in all four patient groups. A 2.1% greater reduction in LDL-C was observed in women, compared with men (p < 0.0001). Patients aged ≥70 years experienced a 2.7% greater reduction in LDL-C compared with younger patients (p < 0.0001). Similar results were also observed for statin-mediated changes in non-HDL-C. Men experienced a significantly greater increase in HDL-C than women, and patients aged ≥70 years achieved a significantly greater increase than younger patients (both p = 0.001). ConclusionsWhile statins improve the lipid profile in all gender and age groups analysed, the improvements are greater in women than in men and in those aged ≥70 years compared with those aged <70 years.

Efficacy of low- and moderate-intensity statins for achieving low- density lipoprotein cholesterol targets in Thai type 2 diabetic patients

BackgroundLow dose statins are commonly used among Asians, because plasma low-density lipoprotein cholesterol (LDL-C) reductions similar to those observed in Westerners are achieved at lower doses. We aimed to assess the efficacy of low- and moderate-intensity statins for achieving plasma lipid targets in Thai type2 diabetes (T2D) and to evaluate factors associated with greater LDL-C reduction by statins.MethodsT2D patients who were treated with low- and moderate-intensity statins at the Siriraj Diabetes Clinic during the January 2013 to December 2014 study period were eligible for inclusion(n = 978), 400 patients were randomly recruited. Patients were classified into 1 of the following 2 groups according to their plasma LDL-C reductions by statins (N = 393); very favorable response (LDL-C reduction ≥50%) or less favorable response (LDL-C reduction <50%).ResultsOf the 400 patients, 41.3% were low-intensity statin users. Mean age was 64.4 ± 12.7 years, 64% were female. Median duration of diabetes was 13.3 years and mean HbA1C was 8.1 ± 1.9%. Plasma LDL-C goal of <100 mg/dl and <70 mg/dl was achieved in 84.3% and 38.0% respectively, with no significant difference between the low- and moderate-intensity statin users. LDL-C reductions ≥50% can be achieved in 38.4%. Factors associated with very favorable responses from statins were age, hypertension, patients with stable or reduced weight, and better glycemic control.ConclusionLow- and moderate-intensity statins achieved plasma LDL-C goal of <100 mg/dl and <70 mg/dl in 84.3%, and 38.4% of the patients respectively. Due to the improved response to lower doses observed in Asians, a titration dosage strategy should be considered.

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone.Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes.Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy.Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Utilidad del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg frente a atorvastatina 80 mg en la reducción de los niveles de colesterol LDL en pacientes con ictus isquémico o ataque isquémico transitorio

After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc <= 70 mg/dL and/or reduction in LDLc >= 50%. Furthermore, safety parameters were assessed. Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated.

Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups

BackgroundEvidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up.MethodsA total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes.FindingsAfter 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1–0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl.ConclusionsThe benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries.Trial RegistrationClinicalTrials.gov NCT00327574

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Trial: Where to Now?

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Trial: Where to Now?

Effects of phenotypic and genotypic factors on the lipid responses to niacin in Chinese patients with dyslipidemia.

The acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2 catalyze the final step in triglycerides biosynthesis. This study examined the relationships of baseline phenotypes and the common polymorphisms in DGAT1 and DGAT2 with the lipid responses to niacin.Lipid responses in Chinese patients with dyslipidemia treated with the extended release (ER) niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks (n = 121, the primary study) or with ER niacin 1500 mg for at least 4 weeks (n = 68, the replication study) were analyzed according to genotypes of DGAT1 rs7003945 T>C and DGAT2 rs3060 T>C polymorphisms.Treatment with ER niacin improved all lipid parameters in both studies. Absolute and percentage changes in lipids were related to their baseline levels, particularly for low-density lipoprotein cholesterol (LDL-C). The DGAT2 rs3060 T>C polymorphism was associated with lower baseline LDL-C, apoB, high-density lipoprotein cholesterol (HDL-C), and apoAI in patients on statin therapy in the primary study. Subjects with the DGAT2 rs3060 T>C variant had less reduction in LDL-C in the primary study and smaller changes in triglyceride and HDL-C in the replication study but these associations became non-significant after adjusting for baseline lipid values. The DGAT1 rs7003945 T>C polymorphism was not related to lipid baseline values or changes in either study. Concomitant statin therapy and lower body weight were also associated with greater reduction in LDL-C.Baseline lipid levels were the main determinants of lipid responses especially for LDL-C. The DGAT2 rs3060 polymorphism might influence the lipid responses depending on baseline phenotype, but this association did not persist after adjustment for the baseline lipid levels.

Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study

The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia. This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis). At week 24, estimated mean (95% CI) changes in LDL-C from baseline were -48.2% (-52.0% to -44.4%) and -2.3% (-7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of -45.9% (-52.5% to -39.3%) (P < .0001). Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups. Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a randomized controlled trial

BackgroundAlthough the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy. PurposeThe Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD. MethodsThe study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis. ConclusionPRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population.

Case management to reduce cardiovascular disease risk in American Indians and Alaska Natives with diabetes: results from the Special Diabetes Program for Indians Healthy Heart Demonstration Project.

We evaluated cardiovascular disease (CVD) risk factors in American Indians/Alaska Natives (AI/ANs) with diabetes in the Special Diabetes Program for Indians Healthy Heart (SDPI-HH) Demonstration Project. Multidisciplinary teams implemented an intensive case management intervention among 30 health care programs serving 138 tribes. The project recruited 3373 participants, with and without current CVD, between 2006 and 2009. We examined data collected at baseline and 1 year later to determine whether improvements occurred in CVD risk factors and in Framingham coronary heart disease (CHD) risk scores, aspirin use, and smoking status. A1c levels decreased an average of 0.2% (P < .001). Systolic and diastolic blood pressure, low-density lipoprotein (LDL) cholesterol, and triglyceride levels decreased, with the largest significant reduction in LDL cholesterol (∆ = -5.29 mg/dL; P < .001). Average Framingham CHD risk scores also decreased significantly. Aspirin therapy increased significantly, and smoking decreased. Participants with more case management visits had significantly greater reductions in LDL cholesterol and A1c values. SDPI-HH successfully translated an intensive case management intervention. Creative retention strategies and an improved understanding of organizational challenges are needed for future Indian health translational efforts.

Association Between Statin Adherence and Cholesterol Level Reduction from Baseline in a Veteran Population

To investigate the association between statin adherence and changes in lipid panel outcomes from baseline in a veteran population. Retrospective cohort study using multiple linear regression models. Veterans Affairs health care system within the Veterans Integrated Service Network 22, a network of Veterans Affairs facilities in the southwest region of the United States that includes Los Angeles, San Diego, Loma Linda, and Long Beach, California, and Las Vegas, Nevada, with an enrollment of approximately 1.4million veterans. A total of 5365 patients who were new statin users between December 1, 2006, and November 30, 2007; 2674 patients were in the adherent group and 2691 were in the nonadherent group. Adherence was determined by the medication possession ratio. Patients were categorized as adherent if the medication possession ratio at follow-up was 0.80 or more. Adherent patients exhibited significant differences in baseline demographic and clinical characteristics than nonadherent patients in our study sample. Baseline laboratory values for adherent patients were significantly lower for low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), non-high-density lipoprotein cholesterol (non-HDL), and total cholesterol levels. The primary outcome was change in LDL level from baseline at 12months. Secondary outcomes were changes in non-HDL and total cholesterol levels from baseline at 12months. Independent variables controlled for in the multiple linear regression included age, sex, body mass index, race-ethnicity, baseline lipid panel (LDL, HDL, total cholesterol, and triglycerides), statin copayment status, income quintile (according to ZIP code median household income), baseline medication count, statin prescribed, and comorbidities. Multiple linear regression revealed that adherent patients demonstrated significantly greater reductions in LDL of 20.98mg/dl versus nonadherent patients (p<0.0001). Adherent patients similarly demonstrated larger reductions of 24.31mg/dl in non-HDL and 24.06mg/dl in total cholesterol versus nonadherent patients (p<0.0001 for both comparisons). Patients adherent to statin therapy had significant associations with clinically relevant reductions in LDL, non-HDL, and total cholesterol from baseline at 12months compared with nonadherent patients when controlling for potential confounders. Adherence to statin therapy may have important consequences in decreasing clinical outcomes such as myocardial infarctions, strokes, and mortality due to large reductions in lipid panel outcomes from baseline at 12months.

Hipercolesterolemia – uma patologia com expressão desde a idade pediátrica

IntroductionHypercholesterolemia results from an alteration, genetic or acquired, in lipoprotein metabolism. Evidence that hypercholesterolemia is associated with the atherosclerotic process from childhood justifies the screening of high-risk children and initiation of therapy at preschool ages. ObjectiveTo assess children referred for pediatric consultations due to hypercholesterolemia. MethodsChildren and adolescents referred for pediatric consultations with a diagnosis of hypercholesterolemia were enrolled. Information on family history and clinical, anthropometric and biochemical parameters was recorded and, when appropriate, molecular study was performed. ResultsA total of 168 children were assessed. Forty-six presented a familial hypercholesterolemia phenotype and in 22 of these, a mutation in the low-density lipoprotein (LDL) receptor gene was identified. The lipid profile of the group with mutations showed significantly higher values of total and non-high-density lipoprotein (HDL) cholesterol compared to the group without mutations (total cholesterol 316.5±75.9 mg/dl vs. 260.9±42,0 mg/dl; non-HDL cholesterol 268.3±72.6 mg/dl vs. 203.5±43.9 mg/dl; p<0.05). Of the total, 55 were prescribed pharmacological therapy and the others underwent diet and exercise interventions only. A greater reduction in LDL cholesterol was observed in individuals under pharmacological therapy compared to those prescribed diet and exercise only (30.3% vs. 18.1%). Drug side effects were insignificant. ConclusionIt is possible to maintain a normal lipid profile in most individuals with familial hypercholesterolemia in order to reduce the risk of early onset of atherosclerosis, which is associated with serious cardiovascular complications from childhood.

Hypercholesterolemia – A disease with expression since childhood

IntroductionHypercholesterolemia results from an alteration, genetic or acquired, in lipoprotein metabolism. Evidence that hypercholesterolemia is associated with the atherosclerotic process from childhood justifies the screening of high-risk children and initiation of therapy at preschool ages. ObjectiveTo assess children referred for pediatric consultations due to hypercholesterolemia. MethodsChildren and adolescents referred for pediatric consultations with a diagnosis of hypercholesterolemia were enrolled. Information on family history and clinical, anthropometric and biochemical parameters was recorded and, when appropriate, molecular study was performed. ResultsA total of 168 children were assessed. Forty-six presented a familial hypercholesterolemia phenotype and in 22 of these, a mutation in the low-density lipoprotein (LDL) receptor gene was identified. The lipid profile of the group with mutations showed significantly higher values of total and non-high-density lipoprotein (HDL) cholesterol compared to the group without mutations (total cholesterol 316.5±75.9 mg/dl vs. 260.9±42.0 mg/dl; non-HDL cholesterol 268.3±72.6 mg/dl vs. 203.5±43.9 mg/dl; p<0.05). Of the total, 55 were prescribed pharmacological therapy and the others underwent diet and exercise interventions only. A greater reduction in LDL cholesterol was observed in individuals under pharmacological therapy compared to those prescribed diet and exercise only (30.3% vs. 18.1%). Drug side effects were insignificant. ConclusionIt is possible to maintain a normal lipid profile in most individuals with familial hypercholesterolemia in order to reduce the risk of early onset of atherosclerosis, which is associated with serious cardiovascular complications from childhood.

Age, abdominal obesity, and baseline high-sensitivity C-reactive protein are associated with low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B responses to ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome

Treatment response to lipid-lowering therapy can vary in patients with the metabolic syndrome (MetS) due to various patient demographic and baseline characteristics. This study assessed the relationships between baseline characteristics and changes in lipid variables, high-sensitivity C-reactive protein (hs-CRP) and attainment of prespecified low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels in MetS patients treated with ezetimibe/simvastatin and atorvastatin. This is a post-hoc analysis of a multicenter, double-blind, randomized, 6-week parallel study in >1000 hypercholesterolemic subjects (median age of 59 years) with MetS and moderately high/high coronary heart disease risk who were treated with ezetimibe/simvastatin (10/20 and 10/40 mg) or atorvastatin (10, 20, 40 mg). Factors that could affect these treatments were assessed by multivariate analysis. Increasing age, abdominal obesity (waist circumference ≥ 40/35 inches for men/women), and lower baseline hs-CRP were significant predictors of greater reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, triglycerides, and very-low-density lipoprotein cholesterol but not for changes in HDL-C or apolipoprotein AI; effects of race and baseline triglycerides, non-HDL-C, LDL-C, or HDL-C levels were more limited. Age ≥ 65 years (versus <65 years) was also associated with significantly greater attainment of all LDL-C and non-HDL-C targets, whereas abdominal obesity, gender (female > male) and lower baseline LDL-C, non-HDL-C, triglycerides, and hs-CRP were associated with improved attainment for some of these targets. Blood pressure, fasting glucose, Homeostasis Model Assessment of Insulin Resistance tertiles, and diabetes did not predict response for any efficacy variable. Ezetimibe/simvastatin treatment (versus atorvastatin) was a significant predictor for change in most efficacy variables. Treatment responses to ezetimibe/simvastatin and atorvastatin in at-risk patients with the MetS were related to age (≥ 65 years), abdominal obesity, and lower baseline hs-CRP. Ezetimibe/simvastatin treatment was found to be consistently more effective than atorvastatin at the specified dose comparisons across these subgroups. The clinical value of predictive factors requires further study in outcome trials.

A telephone-supported cardiovascular lifestyle programme (CLIP) for lipid reduction and weight loss in general practice patients: a randomised controlled pilot trial.

To evaluate a primary prevention care model using telephone support delivered through an existing health call centre to general practitioner-referred patients at risk of developing CVD, using objective measures of CVD risk reduction and weight loss. Participants were randomised into two groups: (i) those receiving a telephone-supported comprehensive lifestyle intervention programme (CLIP: written structured diet and exercise advice, plus seven telephone sessions with the Heart Foundation Health Information Service); and (ii) those receiving usual care from their general practitioner (control: written general lifestyle advice). Fasting plasma lipids, blood pressure, weight, waist circumference and height were assessed on general practice premises by a practice nurse at Weeks 0 and 12. Two general practices in Adelaide, South Australia. Forty-nine men and women aged 48·0 (sd 5·88) years identified by their general practitioner as being at future risk of CVD (BMI = 33·13 (sd 5·39) kg/m2; LDL cholesterol (LDL-C) = 2·66 (sd 0·92) mmol/l). CLIP participants demonstrated significantly greater reductions in LDL-C (estimated mean (EM) = 1·98 (se 0·17) mmol/l) and total cholesterol (EM = 3·61 (se 0·21) mmol/l) at Week 12 when compared with the control group (EM = 3·23 (se 0·18) mmol/l and EM = 4·77 (se 0·22) mmol/l, respectively). There were no significant treatment effects for systolic blood pressure (F(1,45) = 0·28, P = 0·60), diastolic blood pressure (F(1,43) = 0·52, P = 0·47), weight (F(1,42) = 3·63, P = 0·063) or waist circumference (F(1,43) = 0·32, P = 0·577). In general practice patients, delivering CLIP through an existing telephone health service is effective in achieving reductions in LDL-C and total cholesterol. While CLIP may have potential for wider implementation to support primary prevention of CVD, longer-term cost-effectiveness data are warranted.

A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease

The low-density lipoprotein cholesterol (LDL-C) lowering efficacy of switching to ezetimibe/simvastatin (EZ/S) 10/20 mg versus doubling the run-in statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg in subjects with cardiovascular disease (CVD) and diabetes was assessed. Endpoints included percentage change in LDL-C and percentage of patients achieving LDL-C <70 mg/dL. Significantly greater reductions in LDL-C occurred when switching to EZ/S versus statin doubling in the overall population and in subjects treated with simvastatin 20 mg or atorvastatin 10 mg (all p < 0.001). The LDL-C reduction was numerically greater when switching to EZ/S versus switching to rosuvastatin (p = 0.060). Significantly more subjects reached LDL-C <70 mg/dL with EZ/S (54.5%) versus statin doubling (27.0%) or rosuvastatin (42.5%) in the overall population (all p < 0.001) and within each stratum (all p < 0.001). Switching to EZ/S provided significantly greater reductions in LDL-C versus statin doubling and significantly greater achievement of LDL-C targets versus statin doubling or switching to rosuvastatin.

Changes in LDL-C levels and goal attainment associated with addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin compared with titrating statin monotherapy

BackgroundMany high-risk coronary heart disease (CHD) patients on statin monotherapy do not achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals, and combination lipid-lowering therapy may be considered for these individuals. The effect of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin therapy versus titrating these statins on LDL-C changes and goal attainment in CHD or CHD risk-equivalent patients was assessed in a large, managed-care database in the US.MethodsEligible patients (n = 17,830), initially on statin monotherapy who were ≥18 years with baseline and follow-up LDL-C values, no concomitant use of other lipid-lowering therapy, and on lipid-lowering therapy for ≥42 days, were identified between November 1, 2002 and September 30, 2009. The percent change from baseline in LDL-C levels and the odds ratios for attainment of LDL-C <1.8 and <2.6 mmol/L (70 and 100 mg/dL) were estimated using an analysis of covariance and logistic regression, respectively, adjusted for various baseline factors.ResultsLDL-C reductions from baseline and goal attainment improved substantially in patients treated with ezetimibe added onto simvastatin, atorvastatin, or rosuvastatin therapy (n = 2,312) versus those (n = 13,053) who titrated these statins. In multivariable models, percent change from baseline in LDL-C was −13.1% to −14.8% greater for those who added ezetimibe onto simvastatin, atorvastatin, or rosuvastatin versus those who titrated. The odds of attaining LDL-C <1.8 and <2.6 mmol/L (70 and 100 mg/dL) increased by 2.6–3.2-fold and 2.5–3.1-fold, respectively, in patients who added ezetimibe onto simvastatin, atorvastatin, or rosuvastatin versus titrating statins.ConclusionCHD/CHD risk-equivalent patients in a large US managed-care database, who added ezetimibe onto simvastatin, atorvastatin, or rosuvastatin, had greater LDL-C reductions and goal attainment than those who uptitrated these statin therapies. Our study suggests that high-risk CHD patients in need of more intensive LDL-C lowering therapy may benefit by adding ezetimibe onto statin therapy.

Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia

BackgroundSerum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.MethodsWe performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment.ResultsThe least-squares mean (±SE) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (P<0.001) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553. All the patients who received SAR236553, as compared with 52% of those who received 80 mg of atorvastatin plus placebo, attained an LDL cholesterol level of less than 100 mg per deciliter, and at least 90% of the patients who received SAR236553, as compared with 17% who received 80 mg of atorvastatin plus placebo, attained LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter).ConclusionsIn a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT01288469.)

The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin

The bile acid-activated nuclear receptor farnesoid X receptor (FXR) plays an important role in lipid and glucose metabolism, and in addition, it regulates multiple drug transporters involved in statin disposition. We examined whether a functional single nucleotide polymorphism (SNP) in FXR (-1G>T) influenced the lipid-lowering effect of rosuvastatin. In 385 Chinese patients with hyperlipidemia who had been treated with rosuvastatin 10 mg daily for at least 4 weeks, the association between the FXR -1G>T SNP and lipid response to rosuvastatin was analyzed. The FXR -1G>T SNP was not associated with baseline lipids but was significantly associated with the LDL cholesterol (LDL-C) and total cholesterol response to rosuvastatin. Carriers of the T-variant allele (GT+TT = 68+3) had 4.4% (95% CI: 1.2, 7.5%, P = 0.006) and 2.6% (95% CI: 0.3, 5.0%; P < 0.05) greater reductions in LDL-C and total cholesterol, respectively, compared with those with homozygous wild-type alleles. The association between the FXR polymorphism and the LDL-C response to rosuvastatin remained significant after adjusting for other covariants. This association of the variant allele of the FXR -1G>T polymorphism with a greater LDL-C response to rosuvastatin may suggest that this polymorphism influences the expression of the hepatic efflux transporters involved in biliary excretion of rosuvastatin.

Efficacy of simvastatin compared with atorvastatin in patients with hyperlipidaemia in Kurdistan

Background and objectives: Lowering the blood cholesterol and low density lipoprotein levels may reduce the risk of coronary heart disease. This study was designed to evaluate the effect of lipid-lowering therapy by simvastatin 20 mg versus atorvastatin 20mg on patients suffering from hyperlipidemia. Method: This study is 16-weeks duration included 75 patients with hyperlipidemia. Patients were assigned randomly to receive either simvastatin 20 mg/day group (1), or atorvastatin 20 mg/day group (2). After 12 hours fasting, lipid profile, atherogenic index and alanine aminotransferase were assessed for the patients at baseline, 8-weeks and at the end of 16-weeks of treatment. Results: After therapy for both groups of patients, as compared to the levels at the baseline, the serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) were significantly reduced while high density lipoprotein cholesterol (HDL-C) was significantly increased. Serum alanine aminotransferase (ALT) increased by both groups of treatment with no significant differences between the two modes of treatment. Conclusion: After treatment with simvastatin 20 mg and atorvastatin 20 mg, there were a reduction in total cholesterol, triglyceride, LDL-C, and VLDL-C, and an increase in HDL-C in both groups. Comparing the two types of treatment, atorvastatin 20 mg was more effective in lowering triglyceride and VLDL-C than simvastatin 20 mg while Simvastatin led to greater reduction in LDL-C. Both modes of treatment were well tolerated by the patients.