Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness

Taylor, Allen J.; Villines, Todd C.; Stanek, Eric J.; Devine, Patrick J.; Griffen, Len; Miller, Michael; Weissman, Neil J.; Turco, Mark

doi:10.1056/nejmoa0907569

Cited by 592 publications

(396 citation statements)

References 40 publications

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“…171 A placebo-controlled clinical trial by Taylor et al examined whether extended-release niacin slows the progression and/or causes regression of angiographically assessed coronary atherosclerosis. 172 In patients with CHD or high risk of CHD receiving long-term statin therapy, additional treatment with extended-release niacin at a target dose of 2 g daily resulted in a regression of mean carotid intima-media thickness over 14 months. 172 174 A recent meta-analysis of 387 randomized-control trials implied that niacin is effective in reducing the risk of nonfatal myocardial infarction in individuals not treated with a statin, whereas on top of background statin treatment niacin failed to reduce cardiovascular events.…”

Section: Niacinmentioning

confidence: 97%

“…172 In patients with CHD or high risk of CHD receiving long-term statin therapy, additional treatment with extended-release niacin at a target dose of 2 g daily resulted in a regression of mean carotid intima-media thickness over 14 months. 172 174 A recent meta-analysis of 387 randomized-control trials implied that niacin is effective in reducing the risk of nonfatal myocardial infarction in individuals not treated with a statin, whereas on top of background statin treatment niacin failed to reduce cardiovascular events. 175 Thus, available evidence does not support the routine use of niacin and statin combination therapy for the prevention of cardiovascular disease events.…”

Section: Niacinmentioning

confidence: 97%

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Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially antiatherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

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Section: Niacinmentioning

confidence: 97%

Section: Niacinmentioning

confidence: 97%

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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“…Among these 59 surrogate endpoint trials that had a subsequent clinical endpoint trial, in 24 cases the clinical endpoint trial results validated the positive surrogate trials, while in 20 the subsequent clinical endpoint trial was negative (Table 3). 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 A negative surrogate endpoint trial was less likely to be followed by a positive outcome trial and we identified only 3 such examples ( P =0.02, Figure 2). …”

Section: Resultsmentioning

confidence: 99%

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

Bikdeli

Punnanithinont

Akram

et al. 2017

JAHA

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BackgroundSurrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes.Methods and ResultsWe identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine, Lancet, and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints. We tracked for publication of clinical outcome trials on the interventions tested in surrogate trials. We screened 3016 articles and identified 220 surrogate endpoint trials. From the total of 220 surrogate trials, 157 (71.4%) were positive for their primary endpoint. Only 59 (26.8%) surrogate trials had a subsequent clinical outcomes trial. Among these 59 trials, 24 outcomes trial results validated the positive surrogates, whereas 20 subsequent outcome trials were negative following positive results on a surrogate. We identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit. Findings were consistent in a sample cohort of 383 screened articles inclusive of 37 surrogate endpoint trials from 6 other high‐impact journals.ConclusionsAlthough cardiovascular surrogate outcomes trials frequently show superiority of the tested intervention, they are infrequently followed by a prominent outcomes trial. When there was a high‐profile clinical outcomes study, nearly half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it.

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“…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

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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.

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Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness

Abstract: This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)

Cited by 592 publications

References 40 publications

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

Treatment of Risk Factors to Prevent Stroke

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