Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia

Kastelein, John J.P.; Akdim, Fatima; Stroes, Erik S.G.; Zwinderman, Aeilko H.; Bots, Michiel L.; Stalenhoef, Anton F. H.; Visseren, Frank L.J.; Sijbrands, Eric J.G.; Trip, Mieke D.; Stein, Evan A.; Gaudet, Daniel; Duivenvoorden, Raphaël; Veltri, Enrico P.; Marais, Adéle; Groot, Eric de

doi:10.1056/nejmoa0800742

Cited by 1,142 publications

(753 citation statements)

References 34 publications

Supporting

Mentioning

676

Contrasting

Unclassified

Order By: Relevance

“…Over the study period, total gross domestic product‐adjusted costs associated with nonstatins peaked at more than $9 billion in 2008‐2009. The slightly lower rates of nonstatin LLT use seen since then may have been due to a series of trials mostly demonstrating no cardiovascular outcome benefits of nonstatin LLT 3, 4, 5. However, despite weak evidence for clinical improvement from fibrates and net harm from niacin, in 2012‐2013 they accounted for $2.5 billion and $873 million in annual national expenditure, respectively.…”

Section: Discussionmentioning

confidence: 99%

National Trends in Nonstatin Use and Expenditures Among the US Adult Population From 2002 to 2013: Insights From Medical Expenditure Panel Survey

Salami

Warraich

Valero‐Elizondo

et al. 2018

JAHA

103

132

View full text Add to dashboard Cite

BackgroundEvidence supporting nonstatin lipid‐lowering therapy in atherosclerotic cardiovascular disease risk reduction is variable. We aim to examine nonstatin utilization and expenditures in the United States between 2002 and 2013.Methods and ResultsWe used the Medical Expenditure Panel Survey database to estimate national trends in nonstatin use and cost (total and out‐of‐pocket, adjusted to 2013 US dollars using a gross domestic product deflator) among adults 40 years or older. Nonstatin users increased from 3 million (2.5%) in 2002‐2003 (20.1 million prescriptions) to 8 million (5.6%) in 2012‐2013 (45.8 million prescriptions). Among adults with atherosclerotic cardiovascular disease, nonstatin use increased from 7.5% in 2002‐2003 to 13.9% in 2012‐2013 after peaking at 20.3% in 2006‐2007. In 2012‐2013, 15.9% of high‐intensity statin users also used nonstatins, versus 9.7% of low/moderate‐intensity users and 3.6% of statin nonusers. Nonstatin use was significantly lower among women (odds ratio 0.80; 95% confidence interval 0.75‐0.86), racial/ethnic minorities (odds ratio 0.41; 95% confidence interval 0.36‐0.47), and the uninsured (odds ratio 0.47; 95% confidence interval 0.40‐0.56). Total nonstatin expenditures increased from $1.7 billion (out‐of‐pocket cost, $0.7 billion) in 2002‐2003 to $7.9 billion (out‐of‐pocket cost $1.6 billion) in 2012‐2013, as per‐user nonstatin expenditure increased from $550 to $992. Nonstatin expenditure as a proportion of all lipid‐lowering therapy expenditure increased 4‐fold from 8% to 32%.ConclusionsBetween 2002 and 2013, nonstatin use increased by 124%, resulting in a 364% increase in nonstatin‐associated expenditures.

show abstract

Section: Discussionmentioning

confidence: 99%

National Trends in Nonstatin Use and Expenditures Among the US Adult Population From 2002 to 2013: Insights From Medical Expenditure Panel Survey

Salami

Warraich

Valero‐Elizondo

et al. 2018

JAHA

103

132

View full text Add to dashboard Cite

show abstract

“…ENHANCE was an RCT in patients with heterozygous familial hypercholesterolemia (FH) to assess the effect of simvastatin 80 mg plus ezetimibe 10 mg daily versus simvastatin 80 mg alone on the carotid intima-media thickness (cIMT), used as a surrogate marker of subclinical atherosclerosis. Despite a 16.5% greater reduction in LDL-C in the combination therapy arm, no change was observed in the primary outcome, the change from baseline mean cIMT [54]. The trial results generated a great deal of controversy, and several possible explanations were promptly pointed out, including the study population, previous treatment with statins, a relatively short follow-up period, the variability of cIMT measurements, and the possibility that ezetimibe would decrease LDL-C without affecting the atherosclerotic process.…”

Section: Previous Clinical Experience With Simvastatinezetimibe Combimentioning

confidence: 86%

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Ferreira

Silva

2016

Am J Cardiovasc Drugs

View full text Add to dashboard Cite

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and highdensity lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatinezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia. Key PointsStatin-ezetimibe combinations are a realistic treatment option for patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets while receiving statin monotherapy and for patients prone to dose-dependent statin side effects.The IMPROVE-IT trial was the first to demonstrate a reduction in cardiovascular events with ezetimibe.Recently, combination therapy with atorvastatin plus ezetimibe was also associated with greater coronary plaque regression than atorvastatin alone.

show abstract

“…Ezetimibe reduces LDL cholesterol, and a large-scale trial to study its effects on clinical outcome is ongoing, but to date, it has failed to show any effect on measured atherosclerosis biomarkers [54,55]. Niacin (also known as nicotinic acid, vitamin B 3 ) increases HDL cholesterol and reduces LDL cholesterol, but has not been studied in well-designed trials with clinical outcomes.…”

Section: Dyslipidemiamentioning

confidence: 99%

Treatment of Risk Factors to Prevent Stroke

Aoki

Uchino

2011

Neurotherapeutics

View full text Add to dashboard Cite

Much of the decline in stroke incidence and mortality for the past several decades in Western countries has been attributed to better treatment of risk factors. Many epidemiological studies and clinical trials confirmed the importance of managing hypertension. Comparative trials of anti-hypertensive drugs or drug classes have not yielded clear results, but blood pressure variability may play an important role beyond the absolute value of blood pressure. Diabetes therapy remains a conundrum. Although diabetes is clearly a risk factor for ischemic stroke, treatment trials targeting different glycemic goals have not indicated that glucose lowering results in stroke prevention. Trials focused on insulin resistance are ongoing and they may be able to help establish the management of diabetes/impaired glucose tolerance. Evidence for treatment of dyslipidemia has contrasted science to diabetes mellitus. Dyslipidemia has not been strongly or consistently linked to ischemic stroke but the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed the impact of statin treatment in stroke prevention. The results of clinical trials investigating dabigatran and rivaroxaban clearly indicate alternative strategies to vitamin K antagonists in stroke prevention for persons with atrial fibrillation. Evidence for stroke prevention by life style modification, treating metabolic syndrome, sleep disordered breathing, lipoprotein (a), hyperhomocysteinemia, and coagulation disorders are also discussed.

show abstract

Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia

Cited by 1,142 publications

References 34 publications

National Trends in Nonstatin Use and Expenditures Among the US Adult Population From 2002 to 2013: Insights From Medical Expenditure Panel Survey

National Trends in Nonstatin Use and Expenditures Among the US Adult Population From 2002 to 2013: Insights From Medical Expenditure Panel Survey

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Treatment of Risk Factors to Prevent Stroke

Contact Info

Product

Resources

About