Ongoing Statin Therapy Research Articles

Assessing the Incidence of New-onset Diabetes Mellitus with Statin Use: A Systematic Review of the Systematic Reviews and Meta-analyses.

Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.

Statin therapy and its association with long-term survival after colon cancer surgery

BackgroundThe current study aimed to address the clinical equipoise regarding the association of ongoing statin therapy at time of surgery with long-term postoperative mortality rates after elective, curative, surgical resections of colon cancer by analyzing data from a large validated national register. MethodsAll adults with stage I to III colon cancer who underwent elective surgery with curative intent between January 2007 and October 2016 were retrieved from the Swedish Colorectal Cancer Register, a prospectively collected national register. Patients were identified as having ongoing statin therapy if they filled a prescription within 12 months pre- and postoperatively. Study outcomes included 5-year all-cause and cancer-specific postoperative mortality. To reduce the impact of confounding from covariates owing to nonrandomization, the inverse probability of treatment weighting method was used. Subsequently, Cox proportional hazards models were fitted to the weighted cohorts. ResultsIn total, 19,118 patients underwent elective surgery for colon cancer in the specified period, of whom 31% (5,896) had ongoing statin therapy. Despite being older, having a higher preoperative risk, and having more comorbidities, patients with statin therapy had a higher postoperative survival. After inverse probability of treatment weighting, patients with statin therapy displayed a significantly lower mortality risk up to 5 years after surgery for both all-cause (hazard ratio 0.68, 95% confidence interval 0.63–0.74, P < .001) and cancer-specific mortality (hazard ratio 0.76, 95% confidence interval 0.66–0.89, P < .001). ConclusionThe results of this study indicate that statin therapy is associated with a sustained reduction in all-cause and cancer-specific mortality up to 5 years after elective colon cancer surgery. The findings warrant validation in future prospective clinical trials.

Statin Use and Long-Term Mortality after Rectal Cancer Surgery.

Simple SummaryA diagnosis of locally advanced rectal cancer and succeeding surgery remains an area of high postoperative risk for adverse outcomes. The current investigation aims to clarify uncertainty regarding the impact of ongoing statin therapy on postoperative long-term mortality rates after curative surgical resections of rectal cancer by examining data from a large validated national register. It is the first to date to investigate the impact of statin therapy on long-term mortality following curative rectal cancer surgery. Having an ongoing statin prescription was associated with a lower risk of mortality up to five years after surgery. The results should be confirmed in future large, randomized clinical trials.Background: The current study aimed to assess the association between regular statin therapy and postoperative long-term all-cause and cancer-specific mortality following curative surgery for rectal cancer. The hypothesis was that statin exposure would be associated with better survival. Methods: Patients with stage I–III rectal cancer undergoing surgical resection with curative intent were extracted from the nationwide, prospectively collected, Swedish Colorectal Cancer Register (SCRCR) for the period from January 2007 and October 2016. Patients were defined as having ongoing statin therapy if they had filled a statin prescription within 12 months before and after surgery. Cox proportional hazards models were employed to investigate the association between statin use and postoperative five-year all-cause and cancer-specific mortality. Results: The cohort consisted of 10,743 patients who underwent a surgical resection with curative intent for rectal cancer. Twenty-six percent (n = 2797) were classified as having ongoing statin therapy. Statin users had a considerably decreased risk of all-cause (adjusted hazard ratio (HR) 0.66, 95% confidence interval (CI): 0.60–0.73, p < 0.001) and cancer-specific (adjusted HR 0.60, 95% CI: 0.47–0.75, p < 0.001) mortality up to five years following surgery. Conclusions: Statin use was associated with a lower risk of both all-cause and rectal cancer-specific mortality following curative surgical resections for rectal cancer. The findings should be confirmed in future prospective clinical trials.

Morphological stabilization and regression of carotid plaque following therapy with evolocumab in a high‐risk patient

Lipid-lowering therapy is a mainstay for the management of coronary and carotid disease. Actually, progression of atherosclerosis and adverse events are reduced in proportion to the achieved levels of LDL cholesterol (LDL-C). A 67-year-old patient underwent two hospitalizations 6 months apart due to acute coronary syndromes. In the first, PCI with drug-eluting stents (DES) was performed to treat ulcerated stenoses in the left anterior descending artery. In the second, lipid-rich critical disease was found on the right coronary artery and treated with PCI + DES. Later, carotid duplex ultra-sonography (DU) was done due to some episodes of dizziness. It showed an 80% critical stenosis (peak systolic velocity, PSV 239 cm/s) of the left internal carotid artery (LICA) with high-risk features (hypoechogenic and irregular plaque with "fluffy" components). In consideration of the plaque morphology and the unmet LDL-C targets, evolocumab was added to the ongoing statin therapy. In the following months, we observed a parallel trend between carotid plaque regression and LDL-C lowering. Initial plaque remodeling was seen after 5months: the atheroma appeared fibrotic, with no more fluffy components. At 10 months, in conjunction with the achievement of LDL-C goal (23 mg/dl), a fibrocalcific atheroma was observed; PSV, after an initial rise, fell to 229 cm/s. No further cardiovascular event occurred at 46 months. Last DUS showed a 60% fibrocalcific mid LICA stenosis with PSV of 180 cm/s. Our experience highlights the important role of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors in promoting remodeling and hopefully regression of atherosclerotic plaques.

Administration of eicosapentaenoic acid may alter lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease: A pilot 6-month randomized study

BackgroundWe hypothesized that the addition of eicosapentaenoic acid (EPA) to ongoing statin therapy could change the particle heterogeneity of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles, even in stable coronary artery disease (CAD) patients. MethodsWe assigned CAD patients already receiving statin therapy to one of two groups: an EPA group (1800 mg/day; n = 30) and a control group (n = 30). A gel permeation high-performance liquid chromatography method was used to measure the particle concentration and number of lipoprotein subclasses. ResultsIn the EPA group, significant decreases of both the concentration and number of medium LDL (p = 0.0002 and 0.0001), small LDL (p = 0.0004 and 0.0005) and very small LDL (p = 0.0005 and 0.002) particles were observed. Conversely, the concentration and number of large HDL particles increased significantly (p = 0.024 and 0.048). The concentration of very large HDL particles also increased significantly (p = 0.028). Furthermore, significant correlations between the variables that showed significant changes in the LDL and HDL particle subclasses, and the EPA/arachidonic acid (AA) ratio were found. No other significant associations of lipoprotein particle heterogeneity with the serum EPA/AA ratio were noted in either the control group or the EPA group. Interestingly, univariate and multivariate regression analyses revealed that increased serum lecithin–cholesterol acyltransferase activity, a key enzyme of HDL cholesterol efflux, was a predictor for increased above-mentioned HDL particles subclasses. ConclusionsAdministration of EPA might alter both LDL and HDL particle heterogeneity, causing decreased concentration and number of smaller LDL particles and increased concentration and number of larger HDL particles. Furthermore, addition of EPA to ongoing statin therapy appears to be capable of increasing the EPA/AA ratio, which might have an anti-atherosclerotic effect on lipoprotein particle heterogeneity, even in stable CAD patients with well-controlled serum lipid levels. Clinical Trial RegistrationUMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.

Prior adherence to recommended lipid control targets in patients admitted for acute coronary syndrome

Optimal lipid control is difficult to attain. We assessed preadmission achievement of the European Society of Cardiology targets for low-density lipoprotein-cholesterol (LDL-C) control in patients admitted for acute coronary syndrome. Fasting LDL-C levels were measured in 3164 patients admitted between 2010 and 2017. We assessed the frequency of adequate LDL-C control, with targets defined according to individual cardiovascular risk, and the predictors of inadequate control. The median LDL-C value was 104 (80-130) mg/dL. Most patients had high or very high cardiovascular risk and only 34.2% had LDL-C levels below the recommended target for their estimated risk. Achievement of LDL-C goals increased moderately throughout the study period. Adequate LDL-C control was inversely associated with patient risk. Dyslipidemia, active smoking, diabetes mellitus, and body mass index ≥ 25 were independent predictors of inadequate lipid control, while ongoing statin therapy was associated with adequate control. Only slightly more than one third of patients admitted for acute coronary syndrome meet recommended LDL-C targets on admission. There is broad scope for improvement in primary and secondary prevention, especially among patients who are overweight or have other cardiovascular risk factors.

P5325A possible paradoxical association between LDL-cholesterol in myocardial infarction patients and relation to major adverse outcomes - a 10-year nationwide cohort study

Abstract Background Cardiovascular disease (CVD) risk increases with the level of LDL-cholesterol (LDL-C), and LDL-C lowering treatment improves prognosis. Less is known about LDL-C levels at myocardial infarction (MI) admission and long-term prognosis. Purpose To investigate admission LDL-C levels in relation to mortality, recurrent MI and baseline characteristics. Methods Patients admitted with an MI in Sweden and recorded in the MI-registry (SWEDEHEART) 2006–2016 were included and followed until 2018. Associations between baseline LDL-C, mortality and MI were assessed with Cox regression analysis, adjusting for risk factors (eg. age, diabetes, prior CV events) and lipid lowering therapy. Results Of 126,669 patients (median age: 70) admitted with MI, 26.2% (n=32,883) had ongoing statin therapy, and the median LDL-C was 2.96 (interquartile range 2.23, 3.74) mmol/L. During median follow-up of 4.2 years, 31,024 died and 17,896 had an MI (table). Patients with higher LDL-C were younger, had substantially fewer comorbidities such as diabetes and prior CVD (p&lt;0.001). In this analysis there was an interaction with ongoing statin-use (p=0.0025). When dividing patients by LDL-C into quartiles, statin naive in the highest LDL-C quartile (3.95 mmol/L) had a lower risk of death compared to patients in the lowest quartile (2.62 mmol/L) HR 0.86 (95% CI 0.83–0.90). For patients with ongoing statin, the risk was also lower with higher LDL-C (2.84 mmol/L) compared to lower LDL-C (1.72 mmol/L) HR 0.88 (95% CI 0.81–0.96). No association was observed between LDL-C and recurrent MI. Table 1. Event rate for mortality and myocardial infarction (MI) by LDL quartile groups Q1 Q2 Q3 Q4 LDL-C (mmol/L) Statin naive &lt;2.62 2.62–3.26 3.26–3.95 &gt;3.95 Ongoing &lt;1.72 1.72–2.21 2.21–2.84 &gt;2.84 Mortality Statin naive 0.074 (6553) 0.049 (4596) 0.037 (3706) 0.030 (2949) Ongoing 0.10 (3297) 0.075 (2769) 0.062 (2462) 0.055 (2157) MI Statin naive 0.034 (2808) 0.026 (2292) 0.024 (2269) 0.023 (2094) Ongoing 0.064 (1796) 0.055 (1792) 0.048 (1694) 0.044 (1557) Event/year (n of events) stratified by statin treatment at index event. Conclusions In this real-world population with over 126,000 patients and 10 years of follow-up, higher LDL-C at the time of the MI was associated with a markedly better prognosis in patients with and without prior statin therapy. This paradox may, despite adjustment, be caused by a substantially lower CVD baseline risk in patients with higher LDL-C pertaining to a lower burden of risk factors, younger age, and fewer prior CVD events as well as a highly treatable risk factor.

Administration of eicosapentaenoic acid may alter high-density lipoprotein heterogeneity in statin-treated patients with stable coronary artery disease: A 6-month randomized trial

BackgroundCombined statin plus eicosapentaenoic acid (EPA) therapy might be a potentially effective treatment option to prevent coronary artery disease (CAD). The serum EPA/arachidonic acid (AA) ratio has been identified as a potential new risk marker for CAD. Few data exist whether administration of EPA could affect high-density lipoprotein (HDL) particle size. We hypothesized that the addition of EPA to ongoing statin therapy may result in altered HDL heterogeneity. MethodsWe conducted this 6-month, single-center, prospective, randomized open-label clinical trial to investigate the effect of the additional administration of EPA on the HDL heterogeneity (HDL2, HDL3, and HDL2/HDL3 ratio) in stable CAD patients receiving treatment with statins. We assigned stable CAD patients already receiving statin therapy to the EPA group (1800mg/day: n=50) or the control group (n=50). ResultsA significant decrease in the serum HDL3 level (−4.7% vs. −0.5%, p=0.037), but not of the serum HDL2 level, and a significant increase in the HDL2/HDL3 ratio (5.5% vs. −5.1%, p=0.032) were observed in the EPA group as compared to the control group. Multiple regression analysis with adjustments for coronary risk factors identified the achieved EPA/ AA ratio as an independent and significant predictor of an increase of the HDL2/HDL3 ratio (β=0.295, p=0.001). Furthermore, the change in the serum cholesterol ester transfer protein mass was positively correlated with the change in the EPA/AA ratio in the EPA group (r=0.286, p=0.044), but not in the control group (r=0.121, p=0.401). ConclusionAdministration of EPA might decrease the serum HDL3 level, resulting in an increase in the HDL2/HDL3 ratio. Furthermore, increased EPA/AA ratio by the addition of EPA to ongoing statin therapy might be an indicator of an increase in the HDL2/HDL3 ratio, thereby regulating HDL particle size.Clinical Trial Registration: UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452

Cumplimiento previo de los objetivos recomendados de control lipídico para pacientes que ingresan por síndrome coronario agudo

Introduction and objectivesOptimal lipid control is difficult to attain. We assessed preadmission achievement of the European Society of Cardiology targets for low-density lipoprotein-cholesterol (LDL-C) control in patients admitted for acute coronary syndrome. MethodsFasting LDL-C levels were measured in 3164 patients admitted between 2010 and 2017. We assessed the frequency of adequate LDL-C control, with targets defined according to individual cardiovascular risk, and the predictors of inadequate control. ResultsThe median LDL-C value was 104 (80-130) mg/dL. Most patients had high or very high cardiovascular risk and only 34.2% had LDL-C levels below the recommended target for their estimated risk. Achievement of LDL-C goals increased moderately throughout the study period. Adequate LDL-C control was inversely associated with patient risk. Dyslipidemia, active smoking, diabetes mellitus, and body mass index ≥ 25 were independent predictors of inadequate lipid control, while ongoing statin therapy was associated with adequate control. ConclusionsOnly slightly more than one third of patients admitted for acute coronary syndrome meet recommended LDL-C targets on admission. There is broad scope for improvement in primary and secondary prevention, especially among patients who are overweight or have other cardiovascular risk factors.

A Multiregional, Randomized Evaluation of the Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients With Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol

This phase 3, multiregional, randomized, double-blind, placebo-controlled study assessed the efficacy/safety profile of anacetrapib added to ongoing therapy with statin ± other lipid-modifying therapies in patients with hypercholesterolemia who were not at their low-density lipoprotein (LDL-C) goal (as per the National Cholesterol Education Program Adult Treatment Panel III guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of statin ± other lipid-modifying therapies and with LDL-C ≥70 to <115, ≥100 to <145, ≥130, or ≥160mg/dl for very high, high, moderate, or low CHD risk or at LDL-C goal (per CHD risk category) with HDL-C ≤40mg/dl were randomized in a ratio of 1:1 to anacetrapib 100mg (n= 290) or placebo (n= 293) for 24weeks, followed by a 12-week off-drug phase. The co-primary end points were % change from baseline in LDL-C and HDL-C and the safety profile of anacetrapib. Treatment with anacetrapib reduced LDL-C (BQ) by 37% (95% confidence interval-42.5,-31.0) and increased HDL-C by 118% (95% confidence interval 110.6, 125.7) relative to placebo (p <0.001 for both). Anacetrapib also reduced non-HDL-C, apolipoprotein B, and lipoprotein a and increased apolipoprotein AI versus placebo (p <0.001 for all). There were no clinically meaningful differences between the anacetrapib and placebo groups in the % patients who discontinued drug due to an adverse event or in abnormalities in liver enzymes, creatine kinase, blood pressure, electrolytes, or adjudicated cardiovascular events. Treatment with anacetrapib substantially reduced LDL-C and also increased HDL-C and was well tolerated over 24weeks in statin-treated patients with hypercholesterolemia or low HDL-C.

Lipid-modifying efficacy and tolerability of anacetrapib added to ongoing statin therapy in Japanese patients with dyslipidemia

Background and aimsWe aimed to assess the effects of cholesteryl ester transfer protein inhibitor anacetrapib added to statin ± other lipid-modifying therapies (LMT) in Japanese patients with dyslipidemia who were not at their LDL-C goal. MethodsPatients on a stable dose of statin ± other LMT with LDL-C ≥100 mg/dL to <145 mg/dL, ≥120 mg/dL to <165 mg/dL, ≥140 mg/dL or ≥160 mg/dL for patients with a history of coronary heart disease (CHD), high-, moderate- and low-risk patients respectively, were randomized 2:1, stratified by background therapy, to double-blind anacetrapib 100 mg (n = 204) or placebo (n = 103) for 24 weeks, followed by a 28-week open-label extension phase (anacetrapib 100 mg) and a 12-week off-drug safety follow-up phase. The primary endpoint was percent change from baseline in LDL-C (beta-quantification method), as well as the safety profile of anacetrapib at Week 24; HDL-C was a key secondary endpoint. ResultsAnacetrapib 100 mg further reduced LDL-C (38.0%), non-HDL-C (35.1%), ApoB (28.7%), and Lp(a) (48.3%) and increased HDL-C (148.9%) and ApoAI (50.7%) versus placebo (p < 0.001 for all). There were no meaningful differences between the groups in the proportion of patients with liver enzymes elevations (2.0% vs. 0%), creatine kinase elevations overall (0.5% vs. 0%) or with muscle symptoms (0.5% vs. 0%), blood pressure, electrolytes or adjudicated cardiovascular events (0.5% vs. 0%). In the open–label period, sustained effects on lipid parameters were observed with anacetrapib and the treatment was generally well tolerated. ConclusionsLong-term treatment with anacetrapib 100 mg substantially reduced LDL-C, increased HDL-C and was well tolerated in Japanese patients with dyslipidemia (ClinicalTrials.gov number NCT01760460).

Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients with Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol

To assess the effects of anacetrapib added to statin ± other lipid-modifying therapies in patients with hypercholesterolemia and not at their low-density lipoprotein cholesterol (LDL-C) goal (as per National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of moderate/high-intensity statin ± other lipid-modifying therapies with LDL-C ≥70, ≥100, ≥130, or ≥160mg/dl for very high, high, moderate, and low coronary heart disease risk, respectively, or at LDL-C goal with HDL-C ≤40mg/dl, were randomized 1:1:1, stratified by background therapy use, to anacetrapib 100mg (n= 153), anacetrapib 25mg (n= 152), or placebo (n= 154) for 24weeks, followed by a 12-week off-drug reversal phase. The primary end points were percent change from baseline in LDL-C (beta-quantification method) and HDL-C, as well as the safety profile of anacetrapib. Both doses of anacetrapib reduced LDL-C, non-HDL-C, apolipoprotein (Apo) B, and lipoprotein a and increased HDL-C and Apo AI versus placebo (p <0.001 for all). There were no meaningful differences between the anacetrapib 25mg, 100mg, and placebo groups in the proportions of discontinuations due to drug-related adverse events (0.7%, 1.3% vs 1.3%) or in abnormalities in liver enzymes (0%, 0% vs 0.7%), creatine kinase elevations overall (0%, 0.7% vs 0%) or with muscle symptoms (none seen), blood pressure, electrolytes, or adjudicated cardiovascular events (0.7%, 0.7% vs 1.3%). In conclusion, treatment with anacetrapib resulted in substantial reductions in LDL-C and increases in HDL-C and was generally well tolerated.

Impact of Adding Eicosapentaenoic Acid to Statin Therapy on Plasma Pentraxin 3 Level in Patients with Stable Coronary Artery Disease: A 6-Month, Randomized Controlled Study.

We hypothesized that the additional administration of eicosapentaenoic acid (EPA) in patients with stable coronary artery disease (CAD) receiving statin has the potential to lower the serum pentraxin 3 (PTX3) level, an indicator of plaque stabilization. We randomly assigned CAD patients already receiving statin therapy to an EPA group (1800mg/day, n=53) or control group (n=53). No significant difference was found in the change in the plasma PTX3 level between the groups. However, in a subgroup analysis, a significant percentage reduction in the plasma PTX3 level was observed in patients receiving strong statin compared with the patients receiving moderate statin in the EPA group (-5.6 vs. 14.7%, p=0.0082), while no such difference in the percentage change in the plasma PTX3 level was noted between the two same statin subgroups in the control group. A multiple logistic regression analysis identified the addition of EPA to ongoing strong statin treatment as an independent predictor of PTX3 level reduction. Furthermore, even in patients with relatively well-controlled serum lipid levels, pretreatment with EPA added to ongoing statin therapy reduced serum non-high-density lipoprotein cholesterol and triglyceride-rich lipoproteins as residual risk factors. Through this study design, the results could not support the hypothesis that adding EPA in patients with stable CAD receiving varying degrees of statin treatment reduces the plasma PTX3 level comprehensively. However, addition of EPA to ongoing strong statin treatment, but not ongoing moderate statin treatment, may reduce the plasma PTX3 level, possibly leading to coronary plaque stabilization. UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010452.

Different role of achieved LDL-cholesterol and hs-CRP level in future cardiovascular disease outcomes in non-percutaneous coronary intervention patients with ongoing statin therapy of moderate intensity

Different role of achieved LDL-cholesterol and hs-CRP level in future cardiovascular disease outcomes in non-percutaneous coronary intervention patients with ongoing statin therapy of moderate intensity

Impact of prior statin therapy on evaluation of the inflammatory process and cortisol concentration in patients with the first ST-segment elevation myocardial infarction undergoing coronary angioplasty with bare metal stent implantation

Introduction. The aim of the current study was to verify the impact of statin therapy on evaluation of the inflammatory process and cortisol concentration in patients with the first episode of ST-segment elevation myocardial infarction undergoing coronary angioplasty with bare metal stent implantation. Material and methods. The study was designed as a prospective, single-center cohort study, with a total number of 200 patients enrolled between 2005 and 2008. Results. Seventeen patients with ongoing statin therapy and 167 patients without those agents underwent pPCI with BMS implantation. The cortisol concentration on admission was significantly lower in statin therapy subgroup — median 14.9 μg/dL (9.5–23.3 IQR) vs. 28,1 μg/dL (17.2–39.9 IQR) for patients without lipid lowering drug, p = 0.01. The level of cortisol after 23h was also significantly lower in statin receiving subgroup: 10.4 μg/dL (8.3–19 IQR) vs. 17.3 μg/dL (10.1–25.9 IQR) adequately, p = 0.021. Those two groups did not differ significantly in relation to CRP, IL-6, IL-10 concentrations and to anti-inflammatory cytokine ratio [IL-6/IL-10] on admission, after 24h and at discharge. Significant differences were observed in the concentrations of cTnI and activities of CK and CK-MB. Conclusions. Ongoing statin therapy before an episode of myocardial infarction has an influence on cortisol concentration and cardiac markers. No significant effect on serum levels of cytokines has been observed.

Minor Stroke and Transient Ischemic Attack: Research and Practice.

A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA.

Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy

ETC-1002 is an oral, once-daily medication that inhibits adenosine triphosphate citrate lyase, an enzyme upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, to reduce cholesterol biosynthesis. ETC-1002 monotherapy has demonstrated significant reduction in low-density lipoprotein cholesterol (LDL-C) compared with placebo in phase 2 studies. The objective of this study was to compare the lipid-lowering efficacy of ETC-1002 versus placebo when added to ongoing statin therapy in patients with hypercholesterolemia. This phase 2b, multicenter, double-blind trial (NCT02072161) randomized 134 hypercholesterolemic patients (LDL-C, 115 to 220mg/dl) on stable background statin therapy to 12weeks of add-on treatment with ETC-1002 120mg, ETC-1002 180mg, or placebo. The primary efficacy end point was the percent change in calculated LDL-C from baseline to week 12. For LDL-C, the least-squares mean percent change ± standard error from baseline to week 12 was significantly greater with ETC-1002 120mg (-17 ± 4%, p= 0.0055) and ETC-1002 180 mg (-24 ± 4%, p <0.0001) than placebo (-4 ± 4%). ETC-1002 also dose dependently reduced apolipoprotein B by 15% to 17%, non-high-density lipoprotein cholesterol by 14% to 17%, total cholesterol by 13% to 15%, and LDL particle number by 17% to 21%. All these reductions in ETC-1002-treated cohorts were significantly greater than those with placebo. Rates of adverse events (AEs), muscle-related AEs, and discontinuations for AEs with ETC-1002 were similar to placebo. In conclusion, ETC-1002 120mg or 180mg added to stable statin therapy significantly reduced LDL-C compared to placebo and has a similar tolerability profile.

REEVALUATING THE VALUE OF EZETIMIBE IN THE US FOR PATIENTS WITH HISTORY OF CVD BASED ON THE IMPROVE-IT RESULT

The results of the IMPROVE-IT study have shown that addition of ezetimibe (EZ) to ongoing statin therapy provides additional clinical benefit with respect to CVD outcomes. This trial justifies the practice of adding EZ to statin therapy in high risk CVD patients, which prior to IMPROVE-IT, the long

Abstract 16966: Effect of Adding Ezetimibe to Statins versus Statin Monotherapy in Cardiovascular Risk Reduction in Patients With Coronary Artery Disease - A Meta-analysis

Introduction: Statin therapy has been proven to reduce LDL levels and the risk of cardiovascular events. We sought to evaluate the incremental role of Ezetimibe in addition to on-going Statin therapy to assess changes in lipid profile and cardiovascular events. Methods: A comprehensive search in Medline Indexed and Non-indexed was performed to search for randomized controlled trials that examined the role of Ezetimibe plus Statins compared to Statin monotherapy on lipid profile and cardiovascular event rate in patients with coronary artery disease (CAD). We used the mean change for continuous variables and event rates for dichotomous variables for calculating p- values. Results: We included a total of 17 Randomized Control Trials (RCTs) with 22,603 patients, in our meta-analysis. Among these, 15 studies assessed biochemical improvement, whereas 2 RCTs with 18,186 patients evaluated the clinical outcomes. Summary effects were estimated using random effects model. The cumulative estimate showed that addition of Ezetimibe to Statins resulted in an overall mean reduction of total cholesterol (mean change -14.69 mg/dL, 95% CI -18.03, -10.34, p &lt;0.00001), LDL (mean change -12.92 mg/dL, 95% CI -15.5, -12.34, p &lt;0.00001), and triglycerides (mean change -9.94 mg/dL, 95% CI -13.33, -6.55, p &lt;0.00001). However, there was no significant improvement in HDL level. There was also an 11% reduction in mortality with Ezetimibe addition (Odds Ratio 0.89, 95% CI 0.82, 0.96, p =0.002). ConclusioN: In conclusion, addition of Ezetimibe to a Statin in patients with CAD results in a significant reduction in total cholesterol, LDL and triglycerides and also demonstrates a significant mortality benefit.

Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis

Objective: Evaluate the lipid-altering effects of ezetimibe added to ongoing statin therapy, statin titration, switching from statin monotherapy to a more potent statin or to ezetimibe/simvastatin. Methods: A pooled analysis of patient-level data from 17 double-blind, active or placebo-controlled studies of 8667 hypercholesterolemic adults randomized to ezetimibe 10 mg added to ongoing statins, statin titration (doubling), or switching from ongoing statins to rosuvastatin (10 mg) or to ezetimibe/simvastatin (10/20 and 40 mg). Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) was estimated by analysis of variance. Percent of patients who achieved LDL-C and other guideline-recommended targets, and target lipid levels by baseline distance to goal were evaluated. Results: LDL-C percent change from baseline was −26.0 for ezetimibe added to ongoing statin therapy, −27.6 for switching from ongoing statin to ezetimibe/simvastatin, −19.7 for switching to rosuvastatin 10 mg, and −9.7 for dose doubling of the ongoing statin. For patients within 0.8 mmol/L (30 mg/dL) of the target at baseline, LDL-C target attainment rates were 75.9% for adding ezetimibe to ongoing statin, 72.8% for switching to ezetimibe/simvastatin, 61.8% for switching to rosuvastatin, and 44.3% for statin dose-doubling. Similarly, improvements in other lipids and achievement of non-high-density lipoprotein cholesterol and apolipoprotein B targets among this patient group were largest for ezetimibe added to ongoing statins and switching to ezetimibe/simvastatin; switching to rosuvastatin 10 mg and statin dose-doubling were less effective. Conclusions: Adding ezetimibe to ongoing statin therapy appeared to be an effective option for patients who do not achieve lipid-lowering goals on statins alone.