-
British Medical Journal Apr 1971
Topics: Anticholesteremic Agents; Clofibrate; Humans; Lipids; Propionates; Time Factors
PubMed: 5575963
DOI: 10.1136/bmj.2.5755.223-a -
Pharmacological Research Feb 2018Therapeutic interventions aimed at increasing high-density lipoprotein (HDL) levels in order to reduce the residual cardiovascular (CV) risk of optimally drug treated... (Review)
Review
Therapeutic interventions aimed at increasing high-density lipoprotein (HDL) levels in order to reduce the residual cardiovascular (CV) risk of optimally drug treated patients have not provided convincing results, so far. Transfer of cholesterol from extrahepatic tissues to the liver appears to be the major atheroprotective function of HDL, and an elevation of HDL levels could represent an effective strategy. Inhibition of the cholesteryl ester transfer protein (CETP), raising HDL-cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, reduces low-density lipoprotein-cholesterol (LDL-C) and apoB levels, thus offering a promising approach. Despite the beneficial influence on cholesterol metabolism, off-target effects and lack of reduction in CV events and mortality (with torcetrapib, dalcetrapib and evacetrapib) highlighted the complex mechanism of CETP inhibition. After the failure of the above mentioned inhibitors in phase III clinical development, possibly due to the short duration of the trials masking benefit, the secondary prevention REVEAL trial has recently shown that the inhibitor anacetrapib significantly raised HDL-C (+104%), reduced LDL-C (-18%), with a protective effect on major coronary events (RR, 0.91; 95%CI, 0.85-0.97; p = 0.004). Whether LDL-C lowering fully accounts for the CV benefit or if HDL-C-rise is a crucial factor still needs to be determined, although the reduction of non-HDL (-18%) and Lp(a) (-25%), should be also taken into account. In spite of the positive results of the REVEAL Study, Merck decided not to proceed in asking regulatory approval for anacetrapib. Dalcetrapib (Dal-GenE study) and CKD-519 remain the two molecules within this area still in clinical development.
Topics: Animals; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Humans
PubMed: 29287689
DOI: 10.1016/j.phrs.2017.12.028 -
Nutrients Mar 2023Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is... (Review)
Review
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is directly correlated to the risk of CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority of these drugs, in addition to their lipid-lowering properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on the observation that a decrease in lipid levels occurs along with a decrease in inflammation. Insufficient reduction in the inflammation during treatment with lipid-lowering drugs could be one of the explanations for treatment failure and recurrent CVD events. Thus, the aim of this narrative review was to evaluate the anti-inflammatory properties of currently available lipid-lowering medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, and niacin, as well as dietary supplements and novel drugs used in modern times.
Topics: Humans; Proprotein Convertase 9; Cholesterol, LDL; Hypolipidemic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Cardiovascular Diseases; Dietary Supplements; Anticholesteremic Agents
PubMed: 36986246
DOI: 10.3390/nu15061517 -
Circulation Journal : Official Journal... Oct 2021
Topics: Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Asian People; Humans
PubMed: 33980783
DOI: 10.1253/circj.CJ-21-0246 -
Current Atherosclerosis Reports Dec 2023The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS). (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS).
RECENT FINDINGS
Currently, available data on early (in-hospital/discharge) administration of potent lipid-lowering drugs, such as proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in patients during the vulnerable post-ACS phase, have clearly demonstrated clinical efficacy of the "strike early and strike strong" approach not only for rapid reduction of low-density lipoprotein cholesterol (LDL-C) to unprecedentedly low levels, but also for associated favorable composition of coronary plaque. Intensive lipid-lowering therapy with rapid achievement of the LDL-C treatment goal in ACS patients seems reasonable. However, whether such profound LDL-C reduction would result in additional benefit on the reduction of future CV events still has to be established. Thus, data addressing CV outcomes in such vulnerable patients at extreme CV risk are urgently needed.
Topics: Humans; Proprotein Convertase 9; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Acute Coronary Syndrome; Cholesterol, LDL; Hypolipidemic Agents; Anticholesteremic Agents
PubMed: 38015336
DOI: 10.1007/s11883-023-01163-6 -
Vascular Health and Risk Management 2014Medication nonadherence is a prevalent public health issue that contributes to significant medical costs and detrimental health outcomes. This is especially true in... (Review)
Review
Medication nonadherence is a prevalent public health issue that contributes to significant medical costs and detrimental health outcomes. This is especially true in patients with hypercholesterolemia, a condition affecting millions of American adults and one that is associated with increased risk for coronary and cerebrovascular events. Considering the magnitude of outcomes related to this disease, the medical community has placed significant emphasis on addressing the treatment for high cholesterol, and progress has been made in recent years. However, poor adherence to therapy continues to plague health outcomes and more must be understood and done to address suboptimal medication taking. Here we provide an overview of the reasons for poor medication adherence in patients with hypercholesterolemia and describe recent efforts to curb nonadherence. Suggested approaches for improving medication taking in patients with high cholesterol are also provided to guide practitioners, patients, and payers.
Topics: Anticholesteremic Agents; Health Knowledge, Attitudes, Practice; Humans; Hypercholesterolemia; Medication Adherence; Patient Education as Topic; Patients; Risk Factors; Treatment Outcome
PubMed: 25395859
DOI: 10.2147/VHRM.S56056 -
Journal of Cardiology Jan 2018Familial hypercholesterolemia (FH) is a frequent hereditary metabolic disease characterized by high serum low-density lipoprotein (LDL) cholesterol concentration and... (Review)
Review
Familial hypercholesterolemia (FH) is a frequent hereditary metabolic disease characterized by high serum low-density lipoprotein (LDL) cholesterol concentration and premature atherosclerotic cardiovascular disease (ASCVD). The discovery of the LDL receptor as one of the causative genes of FH enabled us to understand the pathophysiology of FH and paved the way for developing statins. Similar to LDL receptor, discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) also created an opportunity for developing its inhibitors. Since PCSK9 degrades LDL receptor protein, inhibiting PCSK9 will be an effective strategy. Evolocumab and alirocumab, anti-PCSK9 antibodies that inhibit binding between PCSK9 and LDL receptors, are now available in Japan. Adding an anti-PCSK9 antibody to standard therapy with statin alone or statin combined with ezetimibe further reduced serum LDL cholesterol levels by around 60% and they significantly decrease cardiovascular event incidence as compared with placebo. Additionally, the strong LDL cholesterol lowering effect of anti-PCSK9 antibody therapies has reportedly enabled the frequency of lipoprotein apheresis to be reduced or to be discontinued. As alternative strategies against PCSK9, antisense oligonucleotide agents that inhibit PCSK9 protein synthesis as well as a small interfering (or short interference) RNA (siRNA) for PCSK9 are also being developed. While relatively high cost can be given as a problem, PCSK9 inhibitors are able to reduce LDL cholesterol dramatically even in FH patients who could not achieve targets until now. To ensure that these drugs are given to the patients who really need them, it is necessary to raise the diagnosis rate and family screening has to be more actively conducted. Finally, it has been reported that PCSK9 is expressed not only in hepatocytes but also in other cells such as epithelial cells in small intestine and vascular smooth muscle cells in atherosclerotic plaque. Further research regarding extra-hepatic pathophysiology of PCSK9 is expected.
Topics: Animals; Anticholesteremic Agents; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; PCSK9 Inhibitors
PubMed: 28784313
DOI: 10.1016/j.jjcc.2017.07.002 -
Arquivos Brasileiros de Cardiologia Jun 2022
Topics: Anticholesteremic Agents; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 35703641
DOI: 10.36660/abc.20220288 -
PharmacoEconomics Mar 2016Food and Drug Administration in the United States has approved the (PCSK9) inhibitors alirocumab and evolocumab as an adjunct to diet and maximally tolerated statin...
Food and Drug Administration in the United States has approved the (PCSK9) inhibitors alirocumab and evolocumab as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (FH) or clinical atherosclerotic cardiovascular disease requiring additional lowering of LDL-C. Evolocumab has also been approved for homozygous FH. Long-term outcomes studies are pending. The drugs are expensive, costing over $12,000 a year. There is concern that these drugs may not provide good value. While this can be studied with cost-effectiveness analysis, this will be challenging to do, especially when considered for therapy in young people which may be life-long. While inexpensive preventative therapies are cost-effective in the young, expensive therapies may not meet a societal willingness-to-pay threshold as the costs are high and accrue immediately, while the benefits may be decades in the future.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cost-Benefit Analysis; Drug Costs; Enzyme Inhibitors; Humans; PCSK9 Inhibitors
PubMed: 26689785
DOI: 10.1007/s40273-015-0355-y -
Ugeskrift For Laeger Aug 2015Patients who take statins frequently experience adverse events, typically muscle symptoms. Some of these patients develop statin intolerance and discontinue the statin... (Review)
Review
Patients who take statins frequently experience adverse events, typically muscle symptoms. Some of these patients develop statin intolerance and discontinue the statin treatment. The treatment of a statin intolerant patient can be difficult. Treatment possibilities include a low dose regimen of statin, possibly in combination with another lipid-lowering agent, most commonly ezetimibe.
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Risk Factors
PubMed: 26324293
DOI: No ID Found