Apolipoprotein B100 is a better treatment target than calculated LDL and non-HDL cholesterol in statin-treated patients

Soran, Handrean; Kwok, See; Dissanayake, Sanjaya; Charlton-Menys, Valentine; Younis, Naveed; Durrington, Paul N.

doi:10.1258/acb.2011.010277

Cited by 21 publications

(17 citation statements)

References 22 publications

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“…Additional evidence supporting the contribution of other lipoproteins, beyond LDL, to increased cardiovascular risk includes an analysis of statin trials, which demonstrated that on-treatment levels of non-HDL-C are more strongly associated with future risk of atherosclerotic CVD events than LDL-C [23]. Also, in statin-treated subjects, some studies have shown that ApoB provides equivalent or superior discrimination of risk [24][25][26][27][28]. Furthermore, patients with an elevated triglyceride concentration have smaller LDL particles resulting in less efficient clearance via hepatic LDL receptors [29,30].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of the Pcsk9 Inhibitor Evolocumab in Patients With Mixed Hyperlipidemia

Rosenson¹,

Jacobson²,

Priess³

et al. 2015

Canadian Journal of Cardiology

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Purpose Evolocumab significantly reduces low-density lipoprotein-cholesterol (LDL-C); we investigated its effects on LDL-C lowering in patients with mixed hyperlipidemia. Methods We compared the efficacy and safety of evolocumab in hypercholesterolemic patients selected from the phase 2 and 3 trials who had fasting triglyceride levels ≥1.7 mmol/L (150 mg/dL elevated triglycerides) and <1.7 mmol/L (without elevated triglycerides). Fasting triglyceride level ≥ 4.5 mmol/ L at screening was an exclusion criterion for these studies, but post-enrollment triglyceride levels may have exceeded 4.5 mmol/L (400 mg/dL). Efficacy was evaluated in four phase 3 randomized studies (n = 1148) and safety from the phase 2 and 3 studies (n = 2246) and their open-label extension studies (n = 1698). Efficacy analyses were based on 12-week studies, while safety analyses included data from all available studies. Treatment differences were calculated vs. placebo and ezetimibe after pooling dose frequencies. Results Mean treatment difference in percentage change from baseline in LDL-C for participants with elevated triglycerides and those without elevated triglycerides (mean of weeks 10 and 12) with evolocumab was approximately −67 % vs. placebo and −42 % vs. ezetimibe (all P < 0.001) compared to −6 % vs. placebo and −39 % vs. ezetimibe, respectively. Treatment differences for evolocumab vs. placebo and ezetimibe followed a similar pattern for non-high-density lipoprotein (HDL-C) and apolipoprotein B. Evolocumab was well tolerated, with balanced rates of adverse events leading to discontinuation of evolocumab vs. comparator (placebo and/or ezetimibe). Conclusion The significant reductions of atherogenic lipids including LDL-C, non-HDL-C, and apolipoprotein B seen with evolocumab are similar in patients with and without mixed hyperlipidemia.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of the Pcsk9 Inhibitor Evolocumab in Patients With Mixed Hyperlipidemia

Rosenson¹,

Jacobson²,

Priess³

et al. 2015

Canadian Journal of Cardiology

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“…There is no ideal, practical lipid measure for monitoring apheresis. APOB measurement may have advantages [48] but APOB in VLDL rebounds more quickly than APOB in LDL. Direct measurement of LDL-C is not widely available.…”

Section: Lipoprotein Targets In Hofhmentioning

confidence: 99%

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

et al. 2016

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This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.

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“…This risk may be reduced by optimizing treatment targets based on apoB measurement [124], particularly with combined dyslipidemia but low HDL-C also has strong links to this residual risk. Statins have a limited effect on HDL-C, whereas niacin reduces TGL and all atherogenic apoB-containing particles as well as raising HDL-C. Over the past decade as the focus has shifted to HDL-C and beyond statins, there has been an exponential rise in research elucidating protective effects of HDL-C and identifying drugs that improve the antiatherogenic qualities of HDL.…”

Section: Expert Opinionmentioning

confidence: 99%

Extended-release niacin with laropiprant: a review on efficacy, clinical effectiveness and safety

Yadav

Younis²,

Hama

et al. 2012

Expert Opinion on Pharmacotherapy

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Niacin has been shown to prevent CV events, reduce mortality and has beneficial effects on vascular endothelial function. Evidence suggests that this is due to its broad-spectrum lipid altering properties, including lowering lipoprotein (a) (Lp(a)), and its pleiotropic actions. While side effects associated with niacin have limited its use in the past, the extended-release formulations and co-administration of LRPT have increased its tolerability, particularly by reducing flushing. The authors advise that ERN should be used in patients with a high risk of cardiovascular disease, who have failed to reach conventional targets.

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Apolipoprotein B100 is a better treatment target than calculated LDL and non-HDL cholesterol in statin-treated patients

Abstract: ApoB offers a more consistent treatment target independent of hypertriglyceridaemia and would obviate technical problems related to high triglycerides.

Cited by 21 publications

References 22 publications

Efficacy and Safety of the Pcsk9 Inhibitor Evolocumab in Patients With Mixed Hyperlipidemia

Efficacy and Safety of the Pcsk9 Inhibitor Evolocumab in Patients With Mixed Hyperlipidemia

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom

Extended-release niacin with laropiprant: a review on efficacy, clinical effectiveness and safety

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