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Journal of the American College of... Apr 2020Mendelian randomization studies and randomized trials have conclusively demonstrated that lower low-density lipoprotein (LDL) cholesterol results in fewer cardiovascular... (Review)
Review
Mendelian randomization studies and randomized trials have conclusively demonstrated that lower low-density lipoprotein (LDL) cholesterol results in fewer cardiovascular events. This review describes key stages in the evolution of LDL cholesterol-lowering treatment. Data from over 25 cardiovascular outcome trials confirm that, within a few years, statins lower the relative risk of major atherosclerotic events by about 22% per 38.7 mg/dl (1 mmol/l) reduction in LDL cholesterol, with similar benefit across patient subgroups. Meta-analyses of these trials have established the safety of statins with regard to nonvascular mortality and cancer. Other agents available for prescription include ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which both reduce major atherosclerotic events in proportion to their effects on LDL cholesterol and have good safety profiles, though PCSK9 inhibitors remain costly. Investigational LDL cholesterol-lowering agents currently being tested in cardiovascular outcome studies are bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor that reduces cholesterol synthesis, and inclisiran, a double-stranded small interfering ribonucleic acid that inhibits PCSK9 synthesis.
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Mendelian Randomization Analysis
PubMed: 32327106
DOI: 10.1016/j.jacc.2019.11.072 -
Revue Medicale Suisse Apr 2017Observational data show a consistent association between elevated low density lipoproteins (LDL-C) and cardiovascular disease (CVD). Reduction of LDL-C reduces the risk...
Observational data show a consistent association between elevated low density lipoproteins (LDL-C) and cardiovascular disease (CVD). Reduction of LDL-C reduces the risk of CVD as has been shown by many trials. Statins are currently the most effective drugs for lowering LDL-C, but can present side effects which might limit the prescribed dosage and prevent patients from reaching the recommended LDL levels. Although treated with statins important residual cardiovascular event risk remains in patients in primary and secondary prevention for CVD. The discovery of protein convertase subtilisin kexin 9 antibodies is a very promising new hypolipidemic treatment and the aim of this review is to explain their mechanism of action and to discuss safety and efficacy results of some phase III studies.
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors
PubMed: 28727332
DOI: No ID Found -
Lakartidningen Feb 2018
Topics: Anticholesteremic Agents; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Medication Adherence; Patient Participation; Patient Reported Outcome Measures; Quality Assurance, Health Care; Registries; Risk Factors; Sweden
PubMed: 29461571
DOI: No ID Found -
Cleveland Clinic Journal of Medicine Nov 2016The association of reduced proprotein convertase subtilisin/kexin type 9 (PCSK9) activity with reduced cardiovascular disease (CVD) events--and the need for add-ons to... (Review)
Review
The association of reduced proprotein convertase subtilisin/kexin type 9 (PCSK9) activity with reduced cardiovascular disease (CVD) events--and the need for add-ons to statin therapy to achieve treatment goals--has led to the rapid development and US Food and Drug Administration (FDA) approval of monoclonal antibody therapies to inhibit PCSK9. Now that PCSK9 inhibitors are approved by the FDA for use in certain patients, data from ongoing long-term clinical trials addressing tolerability, safety, and proof of additional reduction in CVD events are eagerly awaited.
Topics: Anticholesteremic Agents; Cholesterol, LDL; Humans; Hypercholesterolemia; PCSK9 Inhibitors; Polyethylene Glycols; Proteins
PubMed: 27861116
DOI: 10.3949/ccjm.83.s2.05 -
Deutsches Arzteblatt International Oct 2015About 4.6 million persons in Germany are now taking statins, i.e., drugs that inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. Statins lower... (Review)
Review
BACKGROUND
About 4.6 million persons in Germany are now taking statins, i.e., drugs that inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. Statins lower the concentration of low-density lipoproteins (LDL) and thereby lessen the rate of cardiovascular events; the size of this effect depends on the extent of lowering of the LDL cholesterol concentration. Muscle symptoms are a clinically relevant side effect of statin treatment.
METHODS
This review is based on pertinent publications retrieved by a selective literature search, and on the current recommendations of the European Atherosclerosis Society.
RESULTS
At least 5% of patients taking statins have statin-associated muscle symptoms (SAMS). The etiology of SAMS is heterogeneous. SAMS may seriously impair quality of life and cause complications of variable severity, up to and including rhabdomyolysis (in about 1 in 100,000 cases). SAMS often lead to a reduction in the prescribed dose of the statin, while also negatively affecting drug adherence. More than 90% of patients with SAMS can keep on taking statins over the long term and gain the full clinical benefit of statin treatment after a switch to another type of statin or a readjustment of the dose or frequency of administration. If the LDL cholesterol concentration is not adequately lowered while the patient is taking a statin in the highest tolerable dose, combination therapy is indicated.
CONCLUSION
SAMS are important adverse effects of statin treatment because they lessen drug adherence. Patients with SAMS should undergo a thorough diagnostic evaluation followed by appropriate counseling. In most cases, statins can be continued, with appropriate adjustments, even in the aftermath of SAMS.
Topics: Anticholesteremic Agents; Dose-Response Relationship, Drug; Drug Monitoring; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Medical History Taking; Muscular Diseases; Treatment Outcome
PubMed: 26575138
DOI: 10.3238/arztebl.2015.0748 -
In Vivo (Athens, Greece) 2020Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive... (Review)
Review
BACKGROUND/AIM
Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive function based on clinical trials.
MATERIALS AND METHODS
A systematic search concerning original studies from 2015 to 2020 was performed through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The trials enrolled numerous patients and were conducted in different areas of the world. The terms used are cholesterol, lipid-lowering drugs, statins and cognitive function.
RESULTS
Eleven randomized trials met the inclusion criteria. The trials included patients suffering from cardiovascular conditions. In particular, patients with coronary heart disease, coronary heart disease risk equivalents and hypercholesterolemia were tested. The trials included evolocumab, alirocumab, statin, ezetimibe or placebo.
CONCLUSION
Lipid-lowering drugs seem to have no significant effect on neurocognitive function, but further research specifically focused on this matter is needed.
Topics: Anticholesteremic Agents; Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pharmaceutical Preparations
PubMed: 33144414
DOI: 10.21873/invivo.12144 -
Indian Heart Journal Mar 2024Blood cholesterol has firmly been established as a crucial risk factor for the development of atherosclerotic cardiovascular disease (ASCVD) by elegant epidemiological... (Review)
Review
Blood cholesterol has firmly been established as a crucial risk factor for the development of atherosclerotic cardiovascular disease (ASCVD) by elegant epidemiological studies. Naturally, means to reduce blood cholesterol level took the centerstage of research in this field. After initial lukewarm results with nicotinic acid, fibrates and some other agents, statins emerged as the most effective class of medicine to reduce blood cholesterol; in particular, the most atherogenic low density lipoprotein cholesterol (LDL-C). Also, they are very safe and well tolerated. As ASCVD comes in various stages, statins have also been tried in different settings, e.g., primary prevention, secondary prevention, as part of coronary intervention strategy, familial hypercholesterolemia, etc. Almost in all clinical scenarios, statins proved themselves to impart clinical benefit. Though side effects of statins are outweighed by their benefits, nonetheless clinicians should detect the side effects early to avoid major problems.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Cholesterol, LDL; Dyslipidemias; Atherosclerosis; Cardiovascular Diseases; Anticholesteremic Agents
PubMed: 38599727
DOI: 10.1016/j.ihj.2023.11.267 -
The American Journal of Managed Care May 2001The number of statins available to physicians continues to grow, leading to the question: Are all statins alike? Comparisons of side effects and safety profiles and the... (Comparative Study)
Comparative Study Review
The number of statins available to physicians continues to grow, leading to the question: Are all statins alike? Comparisons of side effects and safety profiles and the dose-response relationship among the different drugs show similar results. The cholesterol-lowering action of each depends on its ability to lower low-density lipoprotein cholesterol (LDL-C). On the other hand, the molecular structures of the newer statins are not similar and could have an effect on the mechanism of action of the compounds. Differences in metabolism also suggest the possibility of serious drug-drug interactions, and differences in levels of lipid reduction at varying dosages among the statins point to clinical variation as well.
Topics: Anticholesteremic Agents; Coronary Disease; Humans; Hypercholesterolemia; Lipoproteins, LDL; Lovastatin; Structure-Activity Relationship; United States
PubMed: 11383374
DOI: No ID Found -
International Journal of Molecular... Jul 2023This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an... (Review)
Review
This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22-23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.
Topics: Humans; Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Eicosapentaenoic Acid; Ezetimibe; Fibrinolytic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; PCSK9 Inhibitors; Proprotein Convertase 9; Triglycerides
PubMed: 37511498
DOI: 10.3390/ijms241411739 -
Trends in Cardiovascular Medicine Apr 2020Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) has revolutionized our understanding of cholesterol homeostasis and added to our arsenal against atherosclerotic... (Review)
Review
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) has revolutionized our understanding of cholesterol homeostasis and added to our arsenal against atherosclerotic cardiovascular disease (ASCVD). In a span of approximately 15 years, PCSK9 has morphed from an esoteric and rare cause of familial hypercholesterolemia (FH) into the most efficient cholesterol-lowering target ever known, with the completion of two large scale cardiovascular outcome trials showing positive results. Current Food and Drug Administration (FDA) approved modalities to inhibit PCSK9 are in the form of monoclonal antibodies which display an unparalleled degree of low-density lipoprotein cholesterol (LDL-C) lowering and expand upon the notion that lower LDL-C is better for ASCVD risk reduction. However, the accelerated pace of discovery and therapeutic development has left large gaps in our knowledge regarding the physiology and function of PCSK9. The aim of this review is to provide context to the discovery, history, treatment and current status of PCSK9 and its therapeutic inhibitors and highlight areas of controversy and future directions.
Topics: Anticholesteremic Agents; Biomarkers; Cardiovascular Diseases; Diffusion of Innovation; Dyslipidemias; Humans; Lipids; PCSK9 Inhibitors; Proprotein Convertase 9; Risk Factors; Serine Proteinase Inhibitors; Time Factors; Treatment Outcome
PubMed: 31151804
DOI: 10.1016/j.tcm.2019.05.007