Double-Dose Pravastatin Versus Add-On Ezetimibe with Low-Dose Pravastatin -Effects on LDL Cholesterol, Cholesterol Absorption, and Cholesterol Synthesis in Japanese Patients with Hypercholesterolemia (PEAS study)

Sasaki, Jun; Otonari, Takatoshi; Sawayama, Yasunori; Hata, Shiro; Oshima, Yoshimi; Saikawa, Tetsunori; Biro, Sadatoshi; Kono, Suminori

doi:10.5551/jat.12013

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…These data confirm literature data [35, 36]. Applying our new model, this suggests that the sum of DNCS and net PLCE compensates for the reduction in chol absorption rate.…”

Section: Scientific Evidence For the Proposed Modelsupporting

confidence: 89%

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

Stellaard¹,

Lütjohann²

2017

Cholesterol

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The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

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“…These data confirm literature data [35, 36]. Applying our new model, this suggests that the sum of DNCS and net PLCE compensates for the reduction in chol absorption rate.…”

Section: Scientific Evidence For the Proposed Modelsupporting

confidence: 89%

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

Stellaard¹,

Lütjohann²

2017

Cholesterol

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“…Fourteen studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27] involving 3105 participants were included for final quantitative analysis, among which 1558 (50.18%) participants received ezetimibe and statin combination therapy and 1547 (49.82%) received double-dose statin monotherapy. The average age of participants was 68.2 years with 30.9%-78.9% males.…”

Section: Search Resultsmentioning

confidence: 99%

The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis

Zhu

Yang

et al. 2019

Bosn J of Basic Med Sci

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Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3,105 participants were included in the final analysis; 1,558 (50.18%) participants received ezetimibe and statin combination therapy and 1,547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients co-administered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (p < 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.

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“…Adding ezetimibe resulted in the highest LDL-C reduction rate among these three treatments. Some studies previously reported that adding ezetimibe to the original treatment was more effective in decreasing LDL-C levels than increasing statin doses [15,16].…”

Section: Discussionmentioning

confidence: 99%

Second-line treatments for dyslipidemia in patients at risk of cardiovascular disease

et al. 2014

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Double-Dose Pravastatin Versus Add-On Ezetimibe with Low-Dose Pravastatin -Effects on LDL Cholesterol, Cholesterol Absorption, and Cholesterol Synthesis in Japanese Patients with Hypercholesterolemia (PEAS study)

Abstract: Adding ezetimibe to low-dose pravastatin achieves greater decreases in LDL-C, apo B, and cholesterol absorption markers than doubling the dose of pravastatin.

Cited by 11 publications

References 26 publications

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis

Second-line treatments for dyslipidemia in patients at risk of cardiovascular disease

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