History and development of HMG-CoA reductase inhibitors

Bellosta, Stefano; Paoletti, Rodolfo; Corsini, Alberto

doi:10.1007/978-3-0348-8135-7_1

Cited by 4 publications

(4 citation statements)

References 115 publications

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“…Empirical data suggest that the diffusion of statins has indeed been rapid. While the first statin came on the market in the late 1980s, three statins were in routine clinical use by 1990, and seven were widely prescribed by 2002 (Bellosta, Paoletti, and Corsini 2002). From 1996 to 1999, the use of statins among patients with high cholesterol increased by nearly 400 percent in the United States (Lewin Group 2000).…”

Section: Theory and Backgroundmentioning

confidence: 99%

Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins

2009

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Although fundamental cause theory has been highly influential in shaping the research literature on health disparities, there have been few empirical demonstrations of the theory, particularly in dynamic perspective. In this study, we examine how income disparities in cholesterol levels have changed with the emergence of statins, an expensive and potent new drug technology. Using nationally representative data from 1976 to 2004, we find that income gradients for cholesterol were initially positive, but then reversed and became negative in the era of statin use. While the advantaged were previously more likely to have high levels of cholesterol, they are now less likely. We consider our case study against a broader theoretical framework outlining the relationship between technology innovation and health disparities. We find that the influence of technologies on socioeconomic disparities is subject to two important modifiers: (1) the nature of the technological change and (2) the extent of its diffusion and adoption.

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Section: Theory and Backgroundmentioning

confidence: 99%

Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins

2009

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“…[52][53][54][55] 2. Improvement of endothelial function 7,56 3. Inhibition of smooth muscle cell proliferation 36,45 The concentrations of drugs required to halve SMC proliferation and cholesterol biosynthesis are summarized in Table 4.…”

Section: Effects Of Statins On Arterial Myocyte Proliferationmentioning

confidence: 99%

“…[1][2][3] The beneficial effects of statins are usually assumed to result from their ability to reduce cholesterol synthesis through the competitive inhibition of HMG-CoA reductase. 6,7 However, because mevalonate (MVA), the product of the enzyme reaction, is the precursor not only of cholesterol but also of many nonsteroidal isoprenoid compounds, inhibition of HMG-CoA reductase may result in pleiotropic effects. 6,8 These isoprenoids include isopentenyl adenosine, present in some types of transfer RNA; dolichols, required for glycoprotein synthesis; and polyisoprenoid side chains of ubiquinones, involved in electron transport.…”

mentioning

confidence: 99%

Statins Effect on Smooth Muscle Cell Proliferation

Bellosta

Arnaboldi

Gerosa

et al. 2004

Seminars in Vascular Medicine

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Clinical trials have firmly established that 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) can induce regression of vascular atherosclerosis as well as reduction of cardiovascular-related morbidity and death in patients with and without coronary artery disease. These beneficial effects of statins are usually assumed to result from their ability to reduce cholesterol synthesis. However, because mevalonic acid is the precursor not only of cholesterol but also of many nonsteroidal isoprenoid compounds, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase may result in pleiotropic effects. Indeed, statins can interfere with major events involved in the formation and the evolution of atherosclerotic lesions, such as arterial myocyte migration and proliferation and cholesterol accumulation, independent of their hypolipidemic properties. The aim of this article is to focus on clinical and experimental data that show that statins possess effects beyond cholesterol lowering, particularly on arterial smooth muscle cell proliferation. The contribution of these direct vascular effects to the reduction of cardiovascular events observed in clinical trials with statins represents one of the major challenges for future studies to understand the antiatherosclerotic benefits of these agents.

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“…Lipid-lowering therapies like statins decrease TC and LDL-C [ 9 – 11 ] and reduce the risk of CVD [ 12 ]. Among different available statins, rosuvastatin ranks first in decreasing LDL-C [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Single-Pill Combination of Rosuvastatin and Ezetimibe in Chinese Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Treatment (ROZEL): A Randomized, Double-Blind, Double Dummy, Active-Controlled Phase 3 Clinical Trial

Su,

Liu,

Zhang

et al. 2023

Adv Ther

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Introduction: Many patients with primary hypercholesterolemia do not achieve their plasma low-density lipoprotein cholesterol (LDL-C) goals with statin alone under a recommended dose of statin (e.g., 10 mg rosuvastatin) in China. The objective of this phase III study was to evaluate the efficacy and safety of a new singlepill combination (SPC) of rosuvastatin 10 mg/ ezetimibe 10 mg (R10/E10) in this population. Methods: This was a randomized, double-blind, double-dummy, active-controlled study in patients with primary hypercholesterolemia inadequately controlled with statin alone. The participants were randomized 1:1 to receive SPC R10/E10 or R10. The primary objective was to demonstrate the superiority of SPC R10/E10 vs. R10 in reducing the LDL-C levels after 8 weeks. Results: This trial randomized 305 participants to SPC R10/E10 (n = 153) and R10 (n = 152). The superiority of SPC R10/E10 over R10 was demonstrated with the least square (LS) mean difference of percent change in LDL-C from baseline to week 8: -13.85% (95% confidence interval [CI] -20.15% to -7.56%, P \ 0.0001). The proportion of participants who achieved the LDL-C target (\ 2.6 mmol/l) at week 8 was larger with SPC R10/E10 (n = 80, 54.1%) than with R10 (n = 42, 29.2%) (Odds ratio = 2.80, 95% CI 1.70 to 4.61, P \ 0.0001

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History and development of HMG-CoA reductase inhibitors

Cited by 4 publications

References 115 publications

Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins

Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins

Statins Effect on Smooth Muscle Cell Proliferation

Efficacy and Safety of Single-Pill Combination of Rosuvastatin and Ezetimibe in Chinese Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Treatment (ROZEL): A Randomized, Double-Blind, Double Dummy, Active-Controlled Phase 3 Clinical Trial

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