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The challenge of multiple cardiovascular risk factor control outside Western Europe: Findings from the International ChoLesterol management Practice Study.
Blom, DJ, Santos, RD, Daclin, V, Mercier, F, Ruiz, AJ, Danchin, N, ,
European journal of preventive cardiology. 2020;(13):1403-1411
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Abstract
BACKGROUND Comprehensive control of multiple cardiovascular risk factors reduces cardiovascular risk but is difficult to achieve. DESIGN A multinational, cross-sectional, observational study. METHODS The International ChoLesterol management Practice Study (ICLPS) investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in patients receiving lipid-modifying therapy in countries outside Western Europe. We examined the rate of, and association between, control of multiple risk factors in ICLPS participants with dyslipidaemia, diabetes and hypertension (N = 2377). RESULTS Mean (standard deviation) age of patients was 61.4 (10.4) years; 51.3% were male. Type 2 diabetes was the most common form of diabetes (prevalence, 96.9%). The prevalence of metabolic syndrome was 67.8%, obesity 40.4%, atherosclerotic disease 39.6% and coronary artery disease 33.5%. All patients were at high (38.2%) or very high (61.8%) cardiovascular risk according to ESC/EAS guidelines. Body mass index (BMI) was <25 kg/m2 in 20.3% of patients, 62.8% had never smoked and 25.2% were former smokers. Overall, 12.2% achieved simultaneous control of LDL-C, diabetes and blood pressure. Risk factor control was similar across all participating countries. The proportion of patients achieving individual guideline-specified treatment targets was 43.9% for LDL-C, 55.5% for blood pressure and 39.3% for diabetes. Multiple correspondence analysis indicated that control of LDL-C, control of blood pressure, control of diabetes, BMI and smoking were associated. CONCLUSION Comprehensive control of multiple cardiovascular risk factors in high-risk patients is suboptimal worldwide. Failure to control one risk factor is associated with poor control of other risk factors.
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Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk.
Rosen, JB, Ballantyne, CM, Hsueh, WA, Lin, J, Shah, AK, Lowe, RS, Tershakovec, AM
Lipids in health and disease. 2015;:103
Abstract
BACKGROUND Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS. METHODS This post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg). RESULTS Ezetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥ 40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups. CONCLUSION The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773).
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Effect of atorvastatin on circulating hsCRP concentrations: a sub-study of the achieve cholesterol targets fast with atorvastatin stratified titration (ACTFAST) study.
Gensini, GF, Gori, AM, Dilaghi, B, Rostagno, C, Gaw, A, Blanco-Colio, LM, de Teresa, E, Egido, J, Farsang, C, Leiter, LA, et al
International journal of cardiology. 2010;(3):257-64
Abstract
BACKGROUND Elevated C-reactive protein (CRP) concentration is a risk factor for cardiovascular events that may add prognostic information. Statin treatment is associated with significant reductions in CRP concentrations, which appear to be unrelated to the magnitude of LDL-cholesterol reduction. We investigated the effect of atorvastatin, across its dose range, on high sensitivity (hs)CRP in subjects at high cardiovascular risk. METHODS ACTFAST was a 12 week, prospective, multicenter, open-label trial in which high-risk subjects were assigned a starting dose of atorvastatin (10, 20, 40 or 80 mg/d) based on LDL-C and status of statin use at screening (1345 statin-free [SF] and 772 previously statin-treated [ST]). RESULTS At baseline, ST subjects had significantly lower hsCRP levels than SF subjects (ST group 2.31, 95% CI 2.15, 2.48 mg/L vs. SF group 3.16, 95% CI 2.98, 3.34 mg/L, p<0.05). In the SF group, atorvastatin 10 to 80 mg significantly (p<0.01) reduced hsCRP levels in a dose dependent-manner. In ST group, additional hsCRP reductions were observed over the statin used at baseline, which were not dose-dependent. Atorvastatin significantly decreased hsCRP concentrations in subjects with or without diabetes or the metabolic syndrome. CONCLUSIONS Atorvastatin treatment at different doses, particularly 80 mg, significantly reduced hsCRP serum concentrations. This reduction was observed in both SF and ST groups and was independent of the presence of metabolic syndrome and/or diabetes. The beneficial effect of atorvastatin was evident at 6 weeks, supporting the practice of early introduction of higher doses of atorvastatin in high-risk patients.
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Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus, metabolic syndrome or neither.
Conard, S, Bays, H, Leiter, LA, Bird, S, Lin, J, Hanson, ME, Shah, A, Tershakovec, AM
Diabetes, obesity & metabolism. 2010;(3):210-8
Abstract
AIM: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both associated with increased risk for atherosclerotic coronary heart disease (CHD). Thus, it is useful to know the relative efficacy of lipid-altering drugs in these patient populations. METHODS A double-blind, parallel group trial of adult patients with hypercholesterolaemia at high-CHD risk receiving atorvastatin 40 mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent change from baseline at week 6 was assessed for LDL-C, total cholesterol, HDL-C , non-HDL-C , Apo A-I, Apo B and triglycerides. Safety was monitored through clinical and laboratory adverse events (AEs). RESULTS Compared with doubling atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL-C, triglycerides, Apo B, non-HDL-C, total cholesterol and lipid ratios in the T2DM, MetS and neither groups. Treatment effects were of similar magnitude across patient groups with both treatments, except triglycerides, which were slightly greater in the T2DM and MetS groups vs. neither group. Changes in HDL-C , Apo A-I and high sensitivity C-reactive protein (hs-CRP) were comparable for both treatments in all three groups. Safety and tolerability profiles were generally similar between treatments and across patient groups, as were the incidence of liver and muscle AEs. CONCLUSIONS Compared with doubling atorvastatin to 80 mg, addition of ezetimibe to atorvastatin 40 mg produced greater improvements in multiple lipid parameters in high-CHD risk patients with T2DM, MetS or neither, consistent with the significantly greater changes observed in the full study cohort (clinical trial # NCT00276484).
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Low-density lipoprotein cholesterol reduction and goal achievement with ezetimibe/simvastatin versus atorvastatin or rosuvastatin in patients with diabetes, metabolic syndrome, or neither disease, stratified by National Cholesterol Education Program risk category.
Polis, AB, Abate, N, Catapano, AL, Ballantyne, CM, Davidson, MH, Smugar, SS, Tershakovec, AM
Metabolic syndrome and related disorders. 2009;(6):601-10
Abstract
BACKGROUND Patients with diabetes mellitus (DM) and metabolic syndrome are at increased risk of coronary heart disease (CHD). Studies have shown differential statin efficacy on low-density lipid cholesterol (LDL-C) by CHD risk strata. OBJECTIVE The aim of this study was to evaluate the consistency of effect with ezetimibe/simvastatin (E/S) combination therapy, atorvastatin, or rosuvastatin in patients with DM, metabolic syndrome, or neither condition (No DM/metabolic syndrome), stratified by the National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) CHD risk group. METHODS Post hoc analyses of 2 multicenter, double-blind, randomized, 6-week studies comparing E/S 10/10, 10/20, 10/40, or 10/80 mg with either atorvastatin 10, 20, 40, or 80 mg, or rosuvastatin 10, 20, or 40 mg. Treatments were compared by pooling across all doses for LDL-C reduction and NCEP LDL-C goal attainment in patients with DM, metabolic syndrome without DM, or No DM/metabolic syndrome across NCEP CHD risk strata. RESULTS NCEP LDL-C goal attainment was lowest in the high-risk group with atherosclerotic vascular disease (12-64%) and greatest in the moderate and low-risk groups (84-100%). In contrast, LDL-C reduction was generally similar irrespective of disease or risk subgroup. All treatments were generally well tolerated, with overall similar safety regardless of disease and risk level. CONCLUSIONS In these studies, CHD risk strata were inversely related to the likelihood of attaining NCEP LDL-C goals, but did not appear to affect the percentage LDL-C change from baseline. This demonstrates the need for especially aggressive cholesterol lowering necessary to reach the lower LDL-C goal for high-risk patients.
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Atorvastatin decreases elevated soluble CD40L in subjects at high cardiovascular risk. Atorvastatin on inflammatory markers study: a substudy of ACTFAST.
Blanco-Colio, LM, Martín-Ventura, JL, de Teresa, E, Farsang, C, Gaw, A, Gensini, G, Leiter, LA, Langer, A, Martineau, P, Egido, J, et al
Kidney international. Supplement. 2008;(111):S60-3
Abstract
The CD40/CD40 ligand plays a role in the inflammatory and prothrombotic processes in atherosclerosis. We analyzed whether short-term treatment with atorvastatin affects soluble CD40 ligand (sCD40L) plasma levels in subjects at high cardiovascular risk. sCD40L plasma concentrations were measured in 852 subjects from the Atorvastatin on Inflammatory Markers (AIM) Study, a 12-week prospective multicenter, open-label trial which enrolled statin-free subjects with coronary heart disease (CHD), CHD-equivalent (diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on LDL-C at screening. Overall, sCD40L levels were not different in patients at high cardiovascular risk compared with healthy subjects. When sCD40L levels were divided in quartiles, patients in the highest quartile (N=213) had higher sCD40L concentrations than age- and gender-matched healthy subjects (N=29) (P<0.0001). Interestingly, all doses of atorvastatin significantly diminished sCD40L levels in subjects at the highest quartile. Furthermore, atorvastatin treatment decreased sCD40L more markedly in subjects with metabolic syndrome compared with those without metabolic syndrome. In conclusion, atorvastatin diminishes sCD40L plasma levels, more markedly so in subjects with metabolic syndrome. Our results indicate that short-term treatment with atorvastatin exhibits anti-inflammatory and antithrombotic effects in subjects at high cardiovascular risk.
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Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients: collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study).
Yokote, K, Bujo, H, Hanaoka, H, Shinomiya, M, Mikami, K, Miyashita, Y, Nishikawa, T, Kodama, T, Tada, N, Saito, Y
Atherosclerosis. 2008;(2):345-52
Abstract
AIMS: To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia. METHODS AND RESULTS Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated. CONCLUSION Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.
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Reduction in estimated risk for coronary artery disease after use of ezetimibe with a statin.
Sampalis, JS, Bissonnette, S, Habib, R, Boukas, S, ,
The Annals of pharmacotherapy. 2007;(9):1345-51
Abstract
BACKGROUND The aim of lipid-lowering treatment is to reduce the risk for cardiovascular events. Patients not at target lipid levels while on hydroxymethylglutaryl coenzyme A reductase inhibitors (statin) monotherapy are at increased cardiovascular risk. OBJECTIVE To describe the impact of coadministration of ezetimibe with a statin on the estimated 10 year risk for coronary artery disease (E-R(CAD)) in patients with hypercholesterolemia and above-target low-density lipoprotein cholesterol (LDL-C) levels after statin monotherapy. METHODS Post hoc analysis was conducted of a prospective, open-label, single-cohort, multicenter Canadian study of 953 patients who were treated for 6 weeks with ezetimibe 10 mg/day coadministered with their current statin at an unaltered dose. For each patient, E-R(CAD) at baseline and at 6 weeks was calculated using the Framingham model. The primary outcome measure of the analysis was the change in E-R(CAD). RESULTS A total of 825 patients with data at baseline and 6 weeks were included in the analysis. There were 423 (51.3%) patients with hypertension, 107 (13.0%) with diabetes mellitus but not metabolic syndrome, 160 (19.4%) with metabolic syndrome but not diabetes mellitus, and 235 (28.5%) with both diabetes mellitus and metabolic syndrome. After 6 weeks of ezetimibe coadministration with statin therapy, mean E-R(CAD) was reduced by 4.1% from 15.6% to 11.5%, which is equivalent to a 25.3% risk reduction (p < 0.001). Of the 225 (27.3%) patients with high E-R(CAD) (> or = 20.1%) at baseline, 144 (64.0%) converted to a lower E-R(CAD) category (p < 0.001). Patients with both diabetes mellitus and metabolic syndrome experienced the highest mean percent reduction in E-R(CAD) of -29.4% (p < 0.001). CONCLUSIONS For patients with above-target LDL-C levels while on statin monotherapy, coadministration of ezetimibe with the statin is effective in significantly reducing the E-R(CAD).
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Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome.
Denke, M, Pearson, T, McBride, P, Gazzara, RA, Brady, WE, Tershakovec, AM
Diabetes & vascular disease research. 2006;(2):93-102
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Abstract
This analysis of the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety of ezetimibe 10 mg added to ongoing statin therapy in patients with diabetes, metabolic syndrome without diabetes, or neither disorder who had low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) goals. After six weeks of treatment, ezetimibe added to statin reduced LDL-C in patients with diabetes by 28%, metabolic syndrome by 24%, or neither by 26%, compared with a 3% reduction for placebo for each group. In each group, more patients receiving ezetimibe plus statin reached LDL-C goal (67-74%) compared with those receiving placebo plus statin (19-22%). Other parameters demonstrating greater improvement with ezetimibe included triglycerides, apolipoprotein (Apo)B/Apo A-I ratio, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein. Ezetimibe plus statin was well tolerated in each group. Ezetimibe added to ongoing statin therapy offers a new treatment option that is consistently effective in improvement of lipid profiles and attainment of LDL-C goals in patients with without diabetes or metabolic syndrome.
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Implications from the Air Force/Texas Coronary Atherosclerosis Prevention Study for the Adult Treatment Panel III guidelines.
Clearfield, M, Downs, JR, Lee, M, Langendorfer, A, McConathy, W, Gotto, AM
The American journal of cardiology. 2005;(12):1674-80
Abstract
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) first reported its results in 1998, before the 2001 publication of the National Cholesterol Education Program-Adult Treatment Panel III guidelines (NCEP-ATP III) and 2004 update. Our objective was to investigate the impact of these guidelines on the AFCAPS/TexCAPS cohort. The main outcome measures were the event rates of first acute major coronary events (AMCEs), which were reduced 39% by lovastatin (95% confidence interval [CI] 21% to 53%, p <0.001) in the 65% of the cohort eligible for drug therapy and by 34% (95% CI -9% to 60%, p = 0.108) in the remaining 35% for whom drug therapy was considered optional. The evaluation of other guideline components included a 44% (95% CI 27% to 58%, p <0.001) reduction in AMCEs in subjects with baseline high-density lipoprotein cholesterol <40 mg/dl and a 41% (95% CI 19% to 57%) reduction in AMCEs in subjects with the metabolic syndrome. In the recent update, patients who had a moderately high risk of coronary heart disease and a baseline low-density lipoprotein cholesterol level of 100 to 130 mg/dl could be considered for therapy with a medication to lower the low-density lipoprotein cholesterol level to <100 mg/dl. A total of 334 subjects (5.1%) were in this group, in whom lovastatin reduced the risk of AMCEs by 68% (95% CI 12% to 88%, p = 0.027). However, 21% of the AMCEs were missed by the guidelines. Metabolic syndrome was noted in 48% of these subjects and may help define those in whom treatment with a medication is now considered optional. In conclusion, the ability of the ATP III guidelines and its update has markedly improved our ability to define coronary heart disease risk; however, other components of the guidelines, such as non-high-density lipoprotein cholesterol and the optional low-density lipoprotein cholesterol target goal of <100 mg/dl, still require additional evaluation.