Platelet Receptor Polymorphisms and theirRole in Cardiovascular Disease. Thrombozytare Rezeptor-Polymorphismen und ihre Bedeutungbei kardiovaskularen Erkrankungen

R. B. Zotz; R. E. Scharf

doi:10.1046/j.1439-0477.2002.02101.x

Short- and Midterm Adherence to Platelet P2Y12 Receptor Inhibitors After Percutaneous Coronary Intervention With Drug-Eluting Stents

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420926667 ◽

2020 ◽

Vol 25 (5) ◽

pp. 466-471

Author(s):

Fernando Morita ◽

Mauricio Wajngarten ◽

Marcelo Katz ◽

Miguel Morita Fernandes-Silva ◽

Adriano Caixeta ◽

...

Keyword(s):

Cardiovascular Disease ◽

Percutaneous Coronary Intervention ◽

Antiplatelet Agents ◽

Coronary Intervention ◽

P2y12 Receptor ◽

Drug Eluting Stent ◽

P2y12 Inhibitors ◽

Platelet Receptor ◽

Percutaneous Coronary ◽

Drug Eluting

Introduction/Objectives: In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence. Method: In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence. Results: A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days. Conclusions: We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.

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Intake of Omega-3 Fatty Acids Suppresses Shear-Induced Platelet Aggregation and Reduces Lipid Raft Localization of the Platelet Glycoprotein Ib-IX-V Complex

Blood ◽

10.1182/blood.v118.21.1128.1128 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1128-1128 ◽

Cited By ~ 1

Author(s):

Adam D Munday ◽

Mekdes S Mersha ◽

Douglas Bolgiano ◽

Barbara A. Konkle ◽

Jose A. Lopez

Keyword(s):

Cardiovascular Disease ◽

Fatty Acids ◽

Shear Stress ◽

Platelet Aggregation ◽

Lipid Raft ◽

Platelet Glycoprotein ◽

Omega 3 ◽

Glycoprotein Ib ◽

Platelet Receptor ◽

Platelet Functions

Abstract Abstract 1128 Evidence first emerged in the 1930s that omega-3 (n-3) and omega-6 (n-6) fatty acids (FA) were important for normal health and growth. A 1960s study of Greenland Inuits provided the first evidence that dietary intake of n-3 FA correlated with a reduction in cardiovascular disease. Omega-3 FA (eicosapentaenoic acid [EPA] and docosahexanoic acid [DHA]), along with n-6 FA (chiefly linoleic acid) are fats essential for health, with a minimum recommended intake of 0.2% and 1% of daily calories, respectively; and a healthy ratio of n-6 to n-3 FAs of 1:1 to 1:4. Increased consumption of n-3 FA has recently been shown to correlate with a reduced death rate from coronary heart disease in both healthy individuals and those with pre-existing cardiovascular disease. Cardiovascular diseases, including myocardial infarction and stroke, are precipitated by pathological platelet thrombus formation and are the leading causes of mortality and morbidity in developed countries. In both thrombosis and hemostasis, platelets attach to areas of vessel injury by binding to von Willebrand Factor (VWF) at the injury site. The platelet receptor for VWF is the glycoprotein (GP) Ib-IX-V complex, specifically GPIbα within the complex. This interaction also mediates fluid-phase platelet aggregation in regions of elevated hydrodynamic shear stress, a process called shear-induced platelet aggregation (SIPA). Glycoprotein Ib-IX-V complex functions depend on its localization to lipid raft domains within the plasma membrane, localization mediated by palmitoylation of Cys residues and involving sequences in the subunit transmembrane and cytoplasmic domains. We reasoned that by interfering with palmitoylation or disrupting lipid rafts, or through both mechanisms, n-3 FAs would decrease platelet functions. We therefore studied the effect of n-3 FAs on platelet functions in 12 healthy adult volunteers who ingested 2400 mg of EPA + DHA daily for 2 months. Blood was drawn from the subjects before they began ingesting n-3 FAs (at weeks -4,-3, and -1), then again during the dosing period (weeks 5, 6, and 8). We assessed complete blood counts, and platelet aggregation in response to ADP (2 μM and 20 μM), arachadonic acid (ACA) (250 μg/ml and 500 μg/ml), and shear stress (at shear rates of 2000, 5000 and 10000 s−1). We also assessed GPIb-IX-V lipid raft localization. In the majority of subjects, platelet aggregation after n-3 FA treatment was reduced with low-concentrations of ADP but not with ACA. The most striking effect was on SIPA, which was reduced by 90% (±2% SEM) at 2000 s−1 and 30% (±7% SEM) at 5000 s−1. No post-treatment difference in SIPA was observed at 10000 s−1. After intake of n-3 FAs, the lipid raft content of GPIb-IX-V decreased by 50% while two raft markers, GM1 ganglioside and flotillin, remained unchanged. These findings indicate that n-3 FAs likely suppress several platelet functions, with one of the most striking being decreased adhesive activity, which correlates with decreased raft content of GPIb-IX-V. Thus, the anti-thrombotic effect of n-3 FAs results from a combination of diminished response to some soluble platelet agonists and reduced adhesive capacity. Disclosures: No relevant conflicts of interest to declare.

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