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      Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets’ attainment in subjects with and without type 2 diabetes

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          Abstract

          Background

          This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients.

          Methods

          We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone.

          Results

          We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78–100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from − 3 to − 11%, p < 0.001, HIS + ezetimibe vs. HIS—from − 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a “treat to absolute LDL-cholesterol levels” approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention.

          Conclusions

          Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12933-021-01338-y.

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          Most cited references44

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          2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk

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            2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

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              Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

              Abstract Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
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                Author and article information

                Contributors
                morieri.ml@gmail.com
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                16 July 2021
                16 July 2021
                2021
                : 20
                : 144
                Affiliations
                [1 ]GRID grid.5608.b, ISNI 0000 0004 1757 3470, Department of Medicine, , University of Padova, ; Via Giustiniani 2, 35128 Padua, Italy
                [2 ]CliCon S.R.L. Health Economics & Outcomes Research, Bologna, Italy
                [3 ]Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, Vicenza, Italy
                [4 ]GRID grid.411474.3, ISNI 0000 0004 1760 2630, University Hospital of Padova , ; Padova, Italy
                Author information
                http://orcid.org/0000-0001-6864-0547
                Article
                1338
                10.1186/s12933-021-01338-y
                8283985
                34271920
                fbe1934b-1e2b-4566-a325-c18243337041
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 May 2021
                : 6 July 2021
                Funding
                Funded by: Amgen Italia
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2021

                Endocrinology & Diabetes
                cardiovascular prevention,statins,pcsk9,ezetimibe,gender,hdl
                Endocrinology & Diabetes
                cardiovascular prevention, statins, pcsk9, ezetimibe, gender, hdl

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