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Role of Lipid-Lowering Therapy in Low-Density Lipoprotein Cholesterol Goal Attainment: Focus on Patients With Acute Coronary Syndrome.
Wang, Q, Liang, C
Journal of cardiovascular pharmacology. 2020;(6):658-670
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Abstract
Dyslipidemia is a major risk factor for cardiovascular (CV) disease, which is the leading cause of death globally. Acute coronary syndrome (ACS) is a common cause of death, accounting for nearly half of the global burden of CV mortality. Epidemiologic studies have identified low-density lipoprotein cholesterol (LDL-C) as an independent CV risk factor, and this is now the primary target for initiating and adjusting lipid-lowering therapies in most current guidelines. Evidence from pivotal studies supports the use of high-intensity statin therapy and a lower level for optimal LDL-C in secondary prevention of atherosclerotic CV disease, especially in patients with ACS undergoing percutaneous coronary intervention. However, current research has identified a gap between the target LDL-C goal attainment and target LDL-C levels recommended by the guidelines. Statins have proven benefits in the management of CV disease and are the cornerstone of lipid-lowering management in patients with ACS. Recent randomized controlled trials have also demonstrated the benefits of cholesterol absorption inhibitors and proprotein convertase subtilisin/kexin type 9 inhibitors. This review summarizes the current evidence for LDL-lowering therapy in patients with ACS, with an emphasis on the importance of LDL-C goal attainment, rapid LDL-C lowering, and duration of LDL-C-lowering therapy.
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The Role of Nutraceuticals in the Optimization of Lipid-Lowering Therapy in High-Risk Patients with Dyslipidaemia.
Penson, PE, Banach, M
Current atherosclerosis reports. 2020;(11):67
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Abstract
PURPOSE OF REVIEW We aimed to summarize recent guidelines, position papers, and high-quality clinical research relating the use of nutraceuticals in the management of individuals at high risk of atherosclerotic cardiovascular disease. RECENT FINDINGS It is essential that individuals at high risk of cardiovascular disease receive guideline-directed evidence-based therapies to reduce their risk of morbidity and mortality from cardiovascular events. Compared with conventional therapeutics, nutraceuticals have undergone relatively little investigation in randomized controlled trials. Thus, recommendations for nutraceuticals in international guidelines are rare, and nutraceuticals should not be used preferentially in place of statins. Nevertheless, recent position papers from the International Lipid Expert Panel and clinical evidence from studies of triglyceride reduction by polyunsaturated fatty acid administration demonstrate that nutraceuticals do have an important role in optimizing therapy in individuals at high risk of cardiovascular disease. Roles for nutraceuticals include as follows: (1) managing residual risk associated with lipids other than low-density lipoprotein cholesterol (LDL-C); (2) managing non-lipid-mediated residual risk; (3) optimizing LDL-C treatment in statin intolerance; (4) optimizing LCL-C treatment when add-on therapies for statins are not available; (5) as adjuncts to lifestyle for individuals at high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The strength of evidence for each of these applications is variable. In addition to guideline-directed therapeutics, nutraceuticals may have roles in optimizing preventative therapy and targeting residual risk in individuals at high risk of ASCVD. Application of Good Manufacturing Practice and randomized controlled trials when producing and evaluating nutraceuticals will expand the armoury of evidence-based agents for the prevention of ASCVD.
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Overall Mortality and LDL Cholesterol Reduction in Secondary Prevention Trials of Cardiovascular Disease.
Pedro-Botet, J, López-Miranda, J, Badimón, L, Civeira, F, Guijarro, C, Millán, J, Mostaza, JM, Pintó, X, Valdivielso, P, Masana, L, et al
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(4):325-332
Abstract
Pooled data from randomized clinical trials on lipid-lowering therapy have provided valuable information and clinical insights. Although cardiovascular disease is a common cause of death, mortality data have rarely been prominent in key lipid trials. The 4S, LIPID and HPS trials were the first to demonstrate a reduction in overall mortality. Lower- versus higher-intensity statin trials and non-statin lipid-lowering trials with ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors proved that additional lipid lowering significantly reduces the occurrence of cardiovascular events. However, only the ODYSSEY OUTCOMES trial showed a reduction in all-cause mortality. The aim of the present narrative review was to contrast these results with those of other key lipid trials: those assessing statins compared with placebo, those evaluating intensive- versus moderate-intensity lipid-lowering therapy and, finally, those investigating non-statin lipid-lowering therapies.
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LDL-cholesterol reduction in chronic kidney disease: options beyond statins.
Goonasekera, MA, Mafham, MM, Haynes, RJ
Current opinion in nephrology and hypertension. 2020;(5):480-488
Abstract
PURPOSE OF REVIEW Individuals with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) events. LDL cholesterol (LDL-C) is a key modifiable cause of ASCVD and lowering LDL-C with statins reduces the risk of ASCVD events in a wide range of populations, including those with CKD. This review considers the utility of recently developed nonstatin LDL-C-lowering therapies in CKD. RECENT FINDINGS The cholesterol absorption inhibitor, ezetimibe, reduces LDL-C by 15-20% and is well tolerated in CKD. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) reduce LDL-C by 50-60% and reduce the risk of ASCVD events. However, these agents require self-administration by subcutaneous injection every 2-4 weeks. The PCSK9 synthesis inhibitor, inclisiran, is administered approximately 6 monthly and may be more suitable for widespread use, although outcome trials are awaited. These PCSK9 targeting therapies require no dose adjustment in CKD and have no drug interactions. SUMMARY Statins and ezetimibe are safe and reduce ASCVD risk in CKD populations. PCSK9 targeting agents may be useful in high-risk CKD patients, including those with prior ASCVD.
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Non-HDL or LDL cholesterol in heterozygous familial hypercholesterolaemia: findings of the Simon Broome Register.
Soran, H, Cooper, JA, Durrington, PN, Capps, N, McDowell, IFW, Humphries, SE, Neil, A, ,
Current opinion in lipidology. 2020;(4):167-175
Abstract
PURPOSE OF REVIEW The role of non-HDL-C in the identification and management of lipid disorders is not clearly defined, although UK guidelines recommend its wider use in assessing the need for lipid-lowering therapy and as a treatment target. RECENT FINDINGS We examined the implications of the use of non-HDL-C as opposed to LDL-C in 253 people with hypercholesterolaemia before treatment and 573 after treatment in whom fasting total serum cholesterol, HDL-C and LDL-C had been recorded and the diagnosis of heterozygous familial hypercholesterolemia (heFH) was investigated by genetic testing. The difference and the limits of agreement between non-HDL-C and LDL-C calculated using the Friedewald formula were assessed in those with and without heFH-causing mutations. SUMMARY There were 147 mutation-positive and 106 mutation-negative pretreatment participants and 395 mutation-positive and 178 mutation-negative patients receiving treatment. The difference between non-HDL-C and LDL-C pretreatment in mutation-positive people (mean LDL-C 7.73 mmol/l) was 0.67 mmol/l (95% CI 0.62-0.73) and posttreatment (mean LDL-C 4.71 mmol/l) was 0.62 mmol/l (95% CI 0.59-0.65) with wide limits of agreement of -0.02 to 1.37 and 0.07-1.18 mmol/l, respectively. Among patients with heterozygous familial hypercholesterolaemia, use of estimated LDL-C derived from non-HDL-C in place of calculated LDL-C may result in diagnostic misclassification and difficulty in assessing the true reduction in LDL-C with treatment, because of the wide inter-individual limits of agreement around the mean difference between non-HDL-C and LDL-C.
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PCSK9: from molecular biology to clinical applications.
Malo, J, Parajuli, A, Walker, SW
Annals of clinical biochemistry. 2020;(1):7-25
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An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome.
Drexel, H, Coats, AJS, Spoletini, I, Bilato, C, Mollace, V, Perrone Filardi, P, Rosano, GMC
European heart journal. Cardiovascular pharmacotherapy. 2020;(2):115-121
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Abstract
Benefits and safety on statins have been well-established over 20 years of research. Despite this, the vast majority of patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels. This is mainly due to poor adherence, which is associated with dangerous and sometimes fatal outcomes. To increase adherence and prevent worse outcomes, a combination therapy with lower dosage of statins and new lipid-lowering drugs may be used. However, the implementation of new lipid-lowering drugs in European countries is still at the beginning. For these reasons, the aim of this position paper is to give an up-to-date indication from the ESC Working Group on Cardiovascular Pharmacotherapy in order to discuss the barriers towards statins adherence and new lipid-lowering drugs implementation in Europe.
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Effects of Lipid Lowering Drugs on Arterial Stiffness: One More Way to Reduce Cardiovascular Risk?
Reklou, A, Katsiki, N, Karagiannis, A, Athyros, V
Current vascular pharmacology. 2020;(1):38-42
Abstract
Arterial stiffness (AS) is considered an independent predictor of cardiovascular disease (CVD) events. Among lipid lowering drugs, statins have a beneficial effect on AS, independent of their hypolipidaemic effect. Based on 3 meta-analyses and other studies, this effect is compound- and doserelated. Potent statins at high doses are more effective than less powerful statins. Ezetimibe (± statin) also seems to decrease AS in patients with dyslipidaemia. Fibrates have no effect on AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have data that beneficially affect all AS risk factors, suggesting a beneficial effect on artery compliance. However, there is no direct measurement of their effect on AS indices. In patients with dyslipidaemia, prescribing high dose statins (± ezetimibe) will not only decrease low-density lipoprotein cholesterol levels but also improve AS (in addition to other effects). This effect on AS may contribute to the observed reduction in vascular events.
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Pediatric Dyslipidemia-Beyond Familial Hypercholesterolemia.
Lazarte, J, Hegele, RA
The Canadian journal of cardiology. 2020;(9):1362-1371
Abstract
Dyslipidemia is seen with increasing prevalence in young Canadians, mainly mild to moderate hypertriglyceridemia secondary to obesity. This review focuses on pediatric dyslipidemias excluding familial hypercholesterolemia (FH), but including both severe and mild to moderate hypertriglyceridemia, combined hyperlipidemia, and elevated lipoprotein(a) [Lp(a)]. We suggest that for Canadian children and adolescents with dyslipidemia, atherosclerotic cardiovascular disease (ASCVD) risk assessment should include both low-density lipoprotein cholesterol and triglyceride measurement. To further stratify risk, determination of non-high-density lipoprotein cholesterol is recommended, for both its ability to predict ASCVD and convenience for the patient because fasting is not required. Similarly, apolipoprotein B measurement (fasting or nonfasting), where available, can be helpful. Lp(a) measurement should not be routine in childhood, but it can be considered in special circumstances. After ruling out secondary causes, the foundation for management of pediatric dyslipidemia includes weight regulation, optimizing diet, and increasing activity level. At present, randomized clinical trial data to guide pharmaceutical management of pediatric hypertriglyceridemia or other non-FH pediatric dyslipidemias are scarce. Pharmaceutical management should be reserved for special situations in which risk of complications such as acute pancreatitis or ASCVD over the intermediate term is high and conservative lifestyle-based interventions have been ineffective.
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Highlights of Studies in Cardiovascular Disease Prevention Presented at the 2020 American College of Cardiology Annual Scientific Session.
Jia, X, Al Rifai, M, Liu, J, Agarwala, A, Gulati, M, Virani, SS
Current atherosclerosis reports. 2020;(8):32
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Abstract
PURPOSE OF REVIEW The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC). RECENT FINDINGS The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A Study of Vericiguat in Participants with Heart Failure with Reduce Ejection Fraction [VICTORIA]). In addition, results from the pooled analysis of phase III trials on inclisiran and secondary analysis examining eicosapentaenoic acid levels and cardiovascular outcomes from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) were included. Finally, we discuss studies examining the use of polygenic risk score with low density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) on lifetime cardiovascular risk. The studies presented at the ACC.20/WCC represent notable contributions in the field of CVD prevention.