☆ 4.7 Review

The Effects of Statins, Ezetimibe, PCSK9-Inhibitors, Inclisiran, and Icosapent Ethyl on Platelet Function

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Review Physiology

Vascular smooth muscle cells in intimal hyperplasia, an update

Sebastien Deglise et al.

Summary: Arterial occlusive disease is the leading cause of death in Western countries. Core contemporary therapies suffer from high failure rates due to re-occlusive vascular wall adaptations and restenosis. Restenosis following vascular surgery is largely due to intimal hyperplasia.

FRONTIERS IN PHYSIOLOGY (2023)

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Article Cardiac & Cardiovascular Systems

Lipid-lowering therapy in patients with coronary artery disease undergoing percutaneous coronary interventions in Italy: an expert opinion paper of Interventional Cardiology Working Group of Italian Society of Cardiology

Paolo Calabro et al.

Summary: After PCI, patients are at high risk of developing recurrent cardiovascular events. However, several observational studies have shown suboptimal LDL-C control and poor adherence to statin therapy, despite endorsements from international guidelines.

JOURNAL OF CARDIOVASCULAR MEDICINE (2023)

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Article Oncology

ANCHOR CRC: Results From a Single-Arm , Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAF(V600E)-Mutant Metastatic Colorectal Cancer

Eric Van Cutsem et al.

Summary: This study aimed to evaluate the efficacy, safety, and quality of life of the combination of encorafenib + binimetinib + cetuximab as first-line treatment for BRAF(V600E)-mutated mCRC. The results showed that this combination therapy was effective with a manageable safety profile.

JOURNAL OF CLINICAL ONCOLOGY (2023)

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Article Medicine, General & Internal

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients

S. E. E. Nissen et al.

Summary: This study demonstrates that the ATP citrate lyase inhibitor Bempedoic acid can significantly reduce low-density lipoprotein cholesterol levels and is associated with a low incidence of muscle-related adverse events. Among patients unable or unwilling to take statins, Bempedoic acid treatment significantly reduces the risk of major adverse cardiovascular events.

NEW ENGLAND JOURNAL OF MEDICINE (2023)

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Article Hematology

The association between platelet reactivity and lipoprotein levels in Framingham Heart Study participants

Bongani Brian Nkambule et al.

Summary: This study aimed to assess the association between platelet function and triglyceride levels. The findings showed that triglyceride levels are associated with altered platelet activation and aggregation. Furthermore, increased platelet-driven thrombogenicity is directly associated with triglyceride levels after adjusting for medications and other covariates.

THROMBOSIS RESEARCH (2023)

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Article Cardiac & Cardiovascular Systems

Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT)

Paola Gargiulo et al.

Summary: This study reports the real-world use of PCSK9 inhibitors in patients at high and very-high cardiovascular risk. The results showed that most patients achieved the recommended LDL-cholesterol target and had high adherence and persistence to therapy, regardless of using alirocumab or evolocumab.

ATHEROSCLEROSIS (2023)

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Review Cardiac & Cardiovascular Systems

Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials

Paul Guedeney et al.

Summary: Treatment with alirocumab or evolocumab is associated with reduced risk of myocardial infarction, stroke, and coronary revascularization, with a favorable safety profile.

EUROPEAN HEART JOURNAL (2022)

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Article Cell Biology

Atherosclerosis: nexus of vascular dynamics and cellular cross talks

Divya Dasagrandhi et al.

Summary: Atherosclerosis, characterized by lipid deposition and inflammation in vascular intima, is the main pathology behind cardiovascular diseases. Understanding the pathophysiology of this disease is crucial for early diagnosis and effective treatment.

MOLECULAR AND CELLULAR BIOCHEMISTRY (2022)

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Article Medicine, General & Internal

Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction The PACMAN-AMI Randomized Clinical Trial

Lorenz Raber et al.

Summary: Among patients with acute myocardial infarction, the addition of biweekly subcutaneous alirocumab to high-intensity statin therapy resulted in significantly greater regression of coronary plaques in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2022)

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Article Immunology

Bempedoic acid, an ATP citrate lyase inhibitor, reduces intimal hyperplasia via activation of AMPKα signaling pathway

Wei Liu et al.

Summary: The study demonstrates that bempedoic acid, an ATP citrate lyase (ACLY) inhibitor, reduces ACLY expression to restrain vascular smooth muscle cell (VSMC) proliferation and dedifferentiation. This inhibition is achieved by activating the AMPK/ACC signaling pathway. Bempedoic acid also attenuates neointima formation in wire-injured mouse femoral arteries. These findings suggest that bempedoic acid may serve as a potential therapeutic strategy for diseases associated with intimal hyperplasia.

INTERNATIONAL IMMUNOPHARMACOLOGY (2022)

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Review Medicine, General & Internal

Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias

Clarice Gareri et al.

Summary: The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors, among them hypercholesterolemia has a central role. New technologies such as antisense oligonucleotides and small interfering RNAs (siRNAs) are emerging to block protein translation involved in lipid metabolism.

JOURNAL OF CLINICAL MEDICINE (2022)

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Article Cardiac & Cardiovascular Systems

Independent association of PCSK9 with platelet reactivity in subjects without statin or antiplatelet agents

Shuai Wang et al.

Summary: PCSK9 levels are positively associated with platelet reactivity, which may help explain the beneficial effects of PCSK9 inhibition in reducing the risk of major adverse cardiovascular events after acute coronary syndrome.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2022)

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Article Cardiac & Cardiovascular Systems

Effect of inclisiran, the small-interfering RNA against proprotein convertase subtilisin/kexin type 9, on platelets, immune cells, and immunological biomarkers: a pre-specified analysis from ORION-1

Ulf Landmesser et al.

Summary: The pre-specified safety analysis from ORION-1 for the siRNA therapeutic inclisiran showed no adverse effects on measures of inflammation or immune activation, nor adverse effects on platelets or clinical immunogenicity AEs over at least 6-month treatment, providing strong reassurance about the safety of inclisiran and the potential of cardiovascular RNA-targeted therapies.

CARDIOVASCULAR RESEARCH (2021)

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Review Cardiac & Cardiovascular Systems

Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis

Paul Guedeney et al.

Summary: This study compared the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or established atherosclerotic cardiovascular disease. The results showed that there were no significant differences in efficacy endpoints between the two drugs, except for a better reduction in all-cause death with alirocumab. However, alirocumab had a higher risk of injection site reactions compared to evolocumab.

EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY (2021)

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Article Cardiac & Cardiovascular Systems

Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Subodh Verma et al.

Summary: In patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl in the REDUCE-IT trial led to significant reductions in both first and recurrent ischemic events compared to placebo, with similar safety findings between groups.

CIRCULATION (2021)

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Review Biochemistry & Molecular Biology

The Role of Thromboxane in the Course and Treatment of Ischemic Stroke: Review

Malgorzata Szczuko et al.

Summary: Cardiovascular diseases are leading causes of morbidity and mortality in developed countries, with ischemic stroke being a significant disorder. Acetylsalicylic acid (ASA) is a treatment modality that blocks cyclooxygenase, and measuring thromboxane B2 in serum is a potential biomarker of vascular disease risk. Further research is needed to determine the effectiveness of thromboxane as a clinical marker for ischemic stroke.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cardiac & Cardiovascular Systems

Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study

Stephen J. Nicholls et al.

Summary: The HUYGENS study aims to evaluate the impact of incremental lipid lowering using the PCSK9 inhibitor evolocumab on plaque features in ACS patients treated with statins. The study will use OCT imaging to assess the effects of evolocumab on coronary atherosclerotic plaques, with the primary endpoint being evaluated at baseline and week 50.

CARDIOVASCULAR DIAGNOSIS AND THERAPY (2021)

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Article Multidisciplinary Sciences

Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

Alberto Polimeni et al.

Summary: The study found that severe COVID-19 infection is associated with higher D-dimer values, lower platelet count, and prolonged prothrombin time. These results suggest a possible role of disseminated intravascular coagulation in the pathogenesis of COVID-19 disease complications.

SCIENTIFIC REPORTS (2021)

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Article Biochemistry & Molecular Biology

Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors Reduce Platelet Activation Modulating ox-LDL Pathways

Vittoria Cammisotto et al.

Summary: PCSK9i treatment reduces levels of LDL cholesterol, oxidized LDL, platelet activation, etc., by modulating NOX2 activity and reducing formation of oxidized LDL in patients with HeFH.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

PCSK9 Biology and Its Role in Atherothrombosis

Cristina Barale et al.

Summary: PCSK9 plays a key role in lipoprotein metabolism and atherosclerosis, with potential cardiovascular benefits from its inhibition. Currently, anti-PCSK9 antibodies and small interfering RNA are effective therapies to reduce LDL-C levels and attenuate cardiovascular disease.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology

Sai Sahana Sundararaman et al.

Summary: PCSK9, primarily secreted by hepatocytes, plays a role in regulating the degradation of the LDL receptor. Its effects on cardiovascular complications are not only LDLR-related, but also involve other independent pathways and processes.

BIOMEDICINES (2021)

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Article Cardiac & Cardiovascular Systems

Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up

Cristina Barale et al.

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES (2020)

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Article Cardiac & Cardiovascular Systems

Association of Hypertriglyceridemia with All-Cause Mortality and Atherosclerotic Cardiovascular Events in a Low-Risk Italian Population: The TG-REAL Retrospective Cohort Analysis

Marcello Arca et al.

JOURNAL OF THE AMERICAN HEART ASSOCIATION (2020)

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Article Medicine, General & Internal

Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk The STRENGTH Randomized Clinical Trial

Stephen J. Nicholls et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Article Medicine, General & Internal

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

Deepak L. Bhatt et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Article Pharmacology & Pharmacy

Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of Statins in High-Risk Patients for Cardiovascular Disease

Stefania Tacconelli et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2018)

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Article Medicine, General & Internal

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

G. G. Schwartz et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Review Cardiac & Cardiovascular Systems

Transcatheter aortic valve implantation in patients at intermediate surgical risk

Carmen Spaccarotella et al.

INTERNATIONAL JOURNAL OF CARDIOLOGY (2017)

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Article Cardiac & Cardiovascular Systems

Ezetimibe inhibits platelet activation and uPAR expression on endothelial cells

Tobias Becher et al.

INTERNATIONAL JOURNAL OF CARDIOLOGY (2017)

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Article Cardiac & Cardiovascular Systems

Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9-REACT study

Eliano P. Nayarese et al.

INTERNATIONAL JOURNAL OF CARDIOLOGY (2017)

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Article Medicine, General & Internal

Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial

Robert P. Giugliano et al.

LANCET (2017)

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Article Multidisciplinary Sciences

Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity

Gemma Chiva-Blanch et al.

PLOS ONE (2017)

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Article Cardiac & Cardiovascular Systems

Platelet-Mediated Thrombosis From Bench to Bedside

Paul A. Gurbel et al.

CIRCULATION RESEARCH (2016)

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Article Cardiac & Cardiovascular Systems

Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor? New Insights From the Framingham Offspring Study

Jacquelaine Bartlett et al.

CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES (2016)

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Article Chemistry, Medicinal

Role of Calcium in Platelet Activation: Novel Insights and Pharmacological Implications

Periklis Davlouros et al.

MEDICINAL CHEMISTRY (2016)

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Article Cardiac & Cardiovascular Systems

Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor? New Insights From the Framingham Offspring Study

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CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES (2016)

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Article Medicine, General & Internal

Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

Christopher P. Cannon et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Article Peripheral Vascular Disease

Living the PCSK9 Adventure: from the Identification of a New Gene in Familial Hypercholesterolemia Towards a Potential New Class of Anticholesterol Drugs

Marianne Abifadel et al.

CURRENT ATHEROSCLEROSIS REPORTS (2014)

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Pathophysiology of Atherosclerosis Plaque Progression

Kenichi Sakakura et al.

HEART LUNG AND CIRCULATION (2013)

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Article Hematology

Lipid-lowering therapy with statins reduces microparticle shedding from endothelium, platelets and inflammatory cells

Rosa Suades et al.

THROMBOSIS AND HAEMOSTASIS (2013)

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Article Cardiac & Cardiovascular Systems

Immediate Antioxidant and Antiplatelet Effect of Atorvastatin via Inhibition of Nox2

Pasquale Pignatelli et al.

CIRCULATION (2012)

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Article Cardiac & Cardiovascular Systems

Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Patients With Very High Triglyceride Levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial)

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AMERICAN JOURNAL OF CARDIOLOGY (2011)

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Platelet Reactivity and Cardiovascular Outcomes After Percutaneous Coronary Intervention A Time-Dependent Analysis of the Gauging Responsiveness With a VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) Trial

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CIRCULATION (2011)

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Review Biochemistry & Molecular Biology

Regulators of Platelet cAMP Levels: Clinical and Therapeutic Implications

L. Noe et al.

CURRENT MEDICINAL CHEMISTRY (2010)

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Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials

C. Baigent et al.

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Article Hematology

Antiplatelet Actions of Statins and Fibrates Are Mediated by PPARs

Ferhana Y. Ali et al.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2009)

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Article Hematology

Two distinct roles of mitogen-activated protein kinases in platelets and a novel Rac1-MAPK-dependent integrin outside-in retractile signaling pathway

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BLOOD (2009)

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Article Pharmacology & Pharmacy

Human Platelets Express Organic Anion-Transporting Peptide 2B1, an Uptake Transporter for Atorvastatin

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DRUG METABOLISM AND DISPOSITION (2009)

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Article Pharmacology & Pharmacy

Ezetimibe's effect on platelet aggregation and LDL tendency to peroxidation in hypercholesterolaemia as monotherapy or in addition to simvastatin

Osamah Hussein et al.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2008)

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Article Clinical Neurology

Statin potentiates human platelet eNOS activity without enhancing eNOS mRNA and protein levels

Muge Yemisci et al.

CEREBROVASCULAR DISEASES (2008)

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Article Medicine, General & Internal

Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis

Mitsuhiro Yokoyama et al.

LANCET (2007)

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Article Cardiac & Cardiovascular Systems

Effect of statins on platelet PAR-1 thrombin receptor in patients with the metabolic syndrome (from the PAR-1 inhibition by statins [PARIS] study)

Victor L. Serebruany et al.

AMERICAN JOURNAL OF CARDIOLOGY (2006)

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Article Pathology

Platelet volume indices in patients with coronary artery disease and acute myocardial infarction: an Indian scenario

MM Khandekar et al.

JOURNAL OF CLINICAL PATHOLOGY (2006)

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Review Medicine, Research & Experimental

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M Gawaz et al.

JOURNAL OF CLINICAL INVESTIGATION (2005)

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Article Cardiac & Cardiovascular Systems

Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients

V Sanguigni et al.

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Platelet larger cell ratio (P-LCR) in patients with dyslipidemia

HZW Grotto et al.

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Platelet hyperactivity after statin treatment discontinuation

L Puccetti et al.

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Article Biochemistry & Molecular Biology

Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells

T Nassar et al.

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Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: Downregulatory effect of statin therapy

AG Semb et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2003)

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DD Wagner et al.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2003)

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Article Cardiac & Cardiovascular Systems

Hydroxymethylglutaryl coenzyme a reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation

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A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation

S Massberg et al.

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Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the endocytic itinerary, resulting in retention of low-density lipoprotein on the cell surface

BS Sachais et al.

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Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2000)

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