Browsing by Subject "Anticholesteremic Agents"

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Open Access
A clinician's guide to the ABCs of cardiovascular disease prevention: the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and American College of Cardiology Cardiosource Approach to the Million Hearts Initiative.
(Clinical cardiology, 2013-07) Hsu, Steven; Ton, Van-Khue; Dominique Ashen, M; Martin, Seth S; Gluckman, Ty J; Kohli, Payal; Sisson, Stephen D; Blumenthal, Roger S; Blaha, Michael J
Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. Fortunately, it is often preventable with early adoption of lifestyle modification, prevention of risk factor onset, and aggressive treatment of existing risk factors. The Million Hearts Initiative is an effort by the Centers for Disease Control that aims to prevent 1 million myocardial infarctions and strokes over the next 5 years. As part of this initiative, we present a simply organized "ABCDE" approach for guiding a consistent comprehensive approach to managing cardiovascular risk in daily clinical practice. ABCDE stands for assessment of risk, antiplatelet therapy, blood pressure management, cholesterol management, cigarette/tobacco cessation, diet and weight management, diabetes prevention and treatment, and exercise, interventions regularly used to reduce cardiovascular (CV) risk. Throughout this article we summarize recommendations related to each topic and reference landmark trials and data that support our approach. We believe that the ABCDE approach will be the core framework for addressing CV risk in our effort to prevent CVD.
Open Access
Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function.
(J Am Soc Nephrol, 2017-10) Stanifer, John W; Charytan, David M; White, Jennifer; Lokhnygina, Yuliya; Cannon, Christopher P; Roe, Matthew T; Blazing, Michael A
Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.
Open Access
Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy.
(Clinical cardiology, 2012-01) Kohli, Payal; Desai, Nihar R; Giugliano, Robert P; Kim, Jae B; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M; Scott, Robert; Sabatine, Marc S
Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60-80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein's role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C-lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia.
Open Access
Health beliefs and desire to improve cholesterol levels among patients with hyperlipidemia.
(Patient education and counseling, 2016-05) Zullig, Leah L; Sanders, Linda L; Thomas, Steven; Brown, Jamie N; Danus, Susanne; McCant, Felicia; Bosworth, Hayden B
Objective
Because hyperlipidemia is asymptomatic, many veterans affairs (VA) patients may not perceive it seriously. We assessed key Health Belief model concepts to describe patients' cholesterol-related health beliefs and examine associations between patient-level factors and desire to improve cholesterol control.
Methods
We used baseline data from an ongoing randomized clinical trial. Eligible patients were receiving care at the Durham VA and had CVD risk-total cholesterol levels >130 mg/dL and/or <80% medication adherence in the previous 12 months. A survey assessed patients' health beliefs about high cholesterol and self-reported medication adherence. Multivariable logistic regression examined whether there was an association between desire to control cholesterol and cholesterol status.
Results
Approximately 64% (n=155) of patients perceived high cholesterol as 'very serious'. In multivariable logistic regression analysis, patients who perceived high cholesterol as 'very serious' (OR 2. 26, p=0.032) and/or with high self-efficacy (OR 4.70, p<0.001) had increased odds of desiring cholesterol control.
Conclusion
The factors most significantly associated with desire to improve cholesterol control were perceiving hyperlipidemia as 'very serious and self-efficacy for cholesterol control.
Practice implication
Educating patients, with the goal of appropriately increasing their perceived risk of disease, is likely necessary to impact cholesterol control.
Open Access
Impact of increases in high-density lipoprotein cholesterol on cardiovascular outcomes during the armed forces regression study.
(J Cardiovasc Pharmacol Ther, 2010-12) Devendra, Ganesh P; Whitney, Edwin J; Krasuski, Richard A
INTRODUCTION: high-density lipoprotein (HDL) cholesterol is a well-established inverse risk factor for cardiovascular disease. The extent to which cardiovascular risk can be modified through changes in HDL, however, is less clear. We further examined the role of aggressive HDL raising therapy on cardiovascular outcomes in the 143 patients enrolled in the Armed Forces Regression Study (AFREGS). METHODS: reanalysis of the AFREGS population. Patients with stable coronary disease were randomized to receive gemfibrozil, niacin, and cholestyramine in combination or matching placebos, on top of aggressive dietary and exercise modification for a 30-month period. Blood work was performed at baseline and repeated after 1 year of therapy. RESULTS: patients were divided into 3 groups based on their therapeutic response: no HDL increase, mild HDL increase, and large HDL increase (% change in HDL ≤ 0, ≤ the lower 2 tertiles of HDL increase, and > the upper tertile of HDL increase, respectively). A progressive decrease in cardiovascular events was noted across these groups (30.4%, 19.4%, and 3.2%, respectively, P = .01). Kaplan-Meier analysis according to percentage change in HDL demonstrated a similar improvement in event-free survival (P = .01). Proportional hazards modeling also demonstrated that increasing HDL predicted a lower hazard of cardiovascular events, even after adjusting for changes in low-density lipoprotein ([LDL] P < .01). For every 1% increase in HDL achieved, a 2% decrease in events was recognized. CONCLUSIONS: these data suggest that in a population of patients with stable atherosclerosis, the greater the percentage increase in HDL achieved, the greater the cardioprotective benefit. This further supports HDL raising as a beneficial therapeutic strategy.
Open Access
The effect of gemfibrozil, niacin and cholestyramine combination therapy on metabolic syndrome in the Armed Forces Regression Study.
(Am J Med Sci, 2011-05) Krasuski, Richard A; Devendra, Ganesh P; Cater, George; Whitney, Edwin J
INTRODUCTION: Metabolic syndrome is a powerful predictor of cardiovascular events independent of overt diabetes. Dietary restriction and weight loss modify metabolic syndrome components. This study addresses whether combination pharmacologic therapy focused on dyslipidemia provides additional benefit. METHODS: This study examines the effect of 1 year of gemfibrozil, niacin and cholestyramine therapy on a baseline of aggressive dietary and lifestyle intervention in 143 clinically stable, nondiabetic patients with coronary disease, randomized into a double-blind, placebo-controlled trial. RESULTS: Cohort characteristics included age 63 ± 7 years, 92% men, 43% with previous myocardial infarction, systolic blood pressure 139 ± 17 mm Hg, triglycerides 168 ± 81 mg/dL and high-density lipoprotein cholesterol 34 ± 6 mg/dL. The mean number of metabolic syndrome components decreased from 2.2 ± 0.9 to 1.5 ± 1.1, P < 0.001, and metabolic syndrome prevalence decreased from 38% to 18% (P < 0.001) for the entire cohort. In the lifestyle intervention and placebo group, the mean number of metabolic syndrome components decreased from 2.2 ± 0.9 to 1.9 ± 1.1 (P = 0.01), and prevalence of metabolic syndrome decreased from 44% to 30% (P = 0.15). A far more marked change was observed with lifestyle intervention and pharmacologic therapy: abnormal metabolic components decreased from 2.2 ± 0.9 to 1.0 ± 1.0 (P < 0.001), and prevalence of metabolic syndrome decreased from 32% to 6% (P < 0.001). CONCLUSIONS: The combination of gemfibrozil, niacin and cholestyramine has profound, beneficial effects on the components of metabolic syndrome. These benefits are additive to those seen with aggressive diet and lifestyle modification.
Open Access
Therapy and clinical trials.
(Curr Opin Lipidol, 2013-06) Sodhi, Nishtha; Krasuski, Richard A

Browsing by Subject "Anticholesteremic Agents"

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