Paraoxonase-1 Is Not a Major Determinant of Stent Thrombosis in a Taiwanese Population

BACKGROUND: Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of CYP (CYP 2C19*2, CYP 2C19*3, and CYP 2C19*17), ABCB1 (ABCB1 3435C>T, ABCB1 129T>C, and ABCB1 2677G>T/A), and PON1 (PON1 Q192R, PON1 L55M, and PON1 108C>T) on the development of stent thrombosis (ST) in patients receiving clopidogrel after percutaneous coronary intervention (PCI). METHODS AND RESULTS: We evaluated the incidence of ST (0.64%) in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions). The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of CYP 2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263-9.544; P = 0.031). However, genetic variations in PON1 and ABCB1 showed no significant association with ST. CONCLUSION: We conclude that in a Taiwanese population, PON1 Q192R genotype is not associated with ST development after PCI. However, the presence of CYP 2C19*2 allele is a risk factor for ST development after PCI

P2Y12 platelet inhibition in clinical practice

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines

Clinical Characteristics and Treatment Outcomes of Acute Ischemic Stroke with Atrial Fibrillation Among Patients Admitted to Tertiary Care Hospitals in Amhara Regional State: Retrospective-Cohort Study

Zenaw Debasu Addisu,1,2 Teshale Ayele Mega2 1Department of Pharmacy, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; 2Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Zenaw Debasu Addisu, Email [email protected]: Atrial fibrillation (AF) is the leading cause of a surge in hospital expenses for the treatment of strokes. However, evidence regarding clinical features and survival of patients admitted with acute ischemic stroke (AIS) plus AF in Ethiopia is lacking.Objective: We assess clinical characteristics, survival, and predictors of mortality of patients with acute ischemic stroke and atrial fibrillation among patients admitted to Tertiary Care Hospitals in Amhara regional state.Methods: A retrospective cohort study was done on patients diagnosed with AIS who received care at Tibebe Ghion and Felege Hiwot hospitals from November 2018 to November 2021. Data were analyzed using SPSS version 25. Cox regression analysis was used to identify predictors of in-hospital mortality. Kaplan–Meier analysis was used to identify survival rates and mean survival time. The hazard ratio was used as a measure of the strength of the association and statistical significance was declared at p-value < 0.05.Results: Of 378 patients with AIS, 58.7% were male. AF was diagnosed in 102 (26.9%) patients. Compared with patients without AF, patients with AF were more likely to have Glasgow Coma Scale < 8 (83.3 vs 4%), valvular heart disease (56.9 vs 4.7%), and coronary heart disease (11.8 vs 4%). Patients with AF had a significant incidence of in-hospital mortality (38 per 1000 vs 17 per 1000) person-days. Glasgow Coma Scale < 8: (AHR=12.69, 95% CI: [2.603– 61.873]), aspirational pneumonia (AHR=2.602, 95% CI: 1.085– 6.242), acute renal failure (AHR=6.114, 95% CI: [1.817– 20.576]), hypokalemia (AHR=1.179, 95% CI: [1.112,-3.373]), atrial fibrillation (AHR=1.104, 95% CI: [1.015– 5.404]), HIV/AIDS (AHR=8.302, 95% CI: [1.585– 43.502]) and chronic liver disease (AHR=4.969, 95% CI: [1.192– 20.704]) were indicators of in-hospital mortality.Conclusion: In the current study, hospital mortality was greater in AIS associated with atrial fibrillation. Stroke-related complications were significant predictors of mortality. Hence, effective strategies should be in place to curb the impacts of these factors.Keywords: acute ischemic stroke, atrial fibrillation, clinical characteristic