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Unmet Needs in LDL-C Lowering: When Statins Won't Do!

ABSTRACT: The use of low-density lipoprotein cholesterol (LDL-C)-lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statin therapy, one of the cornerstones for the prevention and treatment of cardiovascular disease (CVD), has been demonstrated to be effective in lowering LDL-C levels and in reducing the risk for CVD and is generally well-tolerated. However, compliance with statins remains suboptimal. One of the main reasons is limitations by adverse events, notably myopathies, which can lead to non-compliance with the prescribed statin regimen. Reducing the burden of elevated LDL-C levels is critical in patients with CVD as well as in patients with very high baseline levels of LDL-C (e.g. patients with familial hypercholesterolaemia), as statin therapy is insufficient for optimally reducing LDL-C below target values. In this review, we discuss alternative treatment options after maximally tolerated doses of statin therapy, including ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and cholesteryl ester transfer protein (CETP) inhibitors. Difficult-to-treat patients may benefit from combination therapy with ezetimibe or a PCSK9 inhibitor (evolocumab or alirocumab, which are now available). Updates of treatment guidelines are needed to guide the management of patients who will best benefit from these new treatments.

SUBMITTER: Krahenbuhl S

PROVIDER: S-EPMC4974266 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Unmet Needs in LDL-C Lowering: When Statins Won't Do!

Krähenbühl Stephan S Pavik-Mezzour Ivana I von Eckardstein Arnold A

Drugs 20160801 12

The use of low-density lipoprotein cholesterol (LDL-C)-lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statin therapy, one of the cornerstones for the prevention and treatment of cardiovascular disease (CVD), has been demonstrated to be effective in lowering LDL-C levels and in reducing the risk for CVD and is generally well-tolerated. However, compliance with statins remains suboptimal. One of the main reasons is limitatio ...[more]

PMID: 27456066

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Project description:BackgroundThere exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks.MethodsLipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin) plus ezetimibe (EAT: n = 53) with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin) (DST: n = 56) in DM subjects who had failed to achieve the optimal LDL-C targets. Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C (remnant like particle cholesterol) and sd-LDL-C, two characteristic atherogenic risks of DM.ResultsThe reduction of LDL-C (%), the primary endpoint, differed significantly between the two groups (-24.6 in EAT vs. -10.9 in DST). In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7) and RLP-C (-19.7 vs. +5.5). In total, 89.4% of the patients receiving EAT reached the optimized treatment goal compared to 51.0% of the patients receiving DST. The changes in TC (-16.3 vs. -6.3) and non-HDL-C (-20.7 vs. -8.3) differed significantly between the two groups.ConclusionEzetimibe added to high-potency statin (10 mg of atorvastatin or 1 mg of pitavastatin) was more effective than the intensified-dose statin (20 mg of atorvastatin or 2 mg of pitavastatin) treatment not only in helping T2DM patients attain more LDL-C reduction, but also in improving their atherogenic lipid profiles, including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response.Trial registrationThe UMIN Clinical Trials Registry UMIN000002593.

Project description:Dermatomyositis is a heterogeneous idiopathic inflammatory myopathy associated with various cutaneous manifestations and variable presence of myositis, interstitial lung disease, and other visceral organ involvement. An accurate diagnosis of dermatomyositis requires correlating clinical examination findings with serological and histological findings. Familiarity with pathognomonic and common cutaneous manifestations of dermatomyositis, which are highlighted here, can be especially helpful in making an accurate diagnosis. Additionally, evaluating patients for presence of myositis-specific autoantibodies can further support or refute a dermatomyositis diagnosis. When present, myositis-specific autoantibodies can also help guide workups for various dermatomyositis-associated manifestations, as each is associated with relatively distinct clinical characteristics. Evaluating patients for various systemic manifestations often relies on expert opinion recommendations; however, societal guideline statements concerning the evaluation of some manifestations have recently been described. Although malignancy-associated dermatomyositis is a well-accepted subtype, there is limited evidence to support extensive malignancy screening has a favorable benefit-risk ratio in most dermatomyositis patients. However, recent research has uncovered novel associations between dermatomyositis and malignancy, suggesting the possibility of identifying high-risk subsets of dermatomyositis patients in whom malignancy screening may have a high value. Treatment for dermatomyositis has remained largely unchanged over the past several decades. Although many dermatomyositis patients can be effectively treated with current options, either as monotherapy or with combination regimens, there is a need for more targeted and effective DM therapies, in general, and for MDA5(+) dermatomyositis-associated rapidly progressive interstitial lung disease. Fortunately, significant current and emerging research activities evaluating various novel medications for dermatomyositis provide hope for exciting future advances in patients with this intriguing immune-mediated disease.

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Unmet Needs in LDL-C Lowering: When Statins Won't Do!

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Unmet Needs in LDL-C Lowering: When Statins Won't Do!

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