Superiority of cilostazol among antiplatelet FDA-approved drugs against COVID 19 Mpro and spike protein: Drug repurposing approach.

Coronavirus disease 2019 (COVID 19) was first identified in Wuhan, China near the end of 2019. To date, COVID-19 had spread to almost 235 countries and territories due to its highly infectious nature. Moreover, there is no vaccine or Food and Drug Administration (FDA)-approved drug. More time is needed to establish one of them. Consequently, the drug repurposing approach seems to be the most attractive and quick solution to accommodate this crisis. In this regard, we performed molecular docking-based virtual screening of antiplatelet FDA-approved drugs on the key two viral target proteins: main protease (Mpro ) and spike glycoprotein (S) as potential inhibitor candidates for COVID-19. In the present study, 15 antiplatelet FDA-approved drugs were investigated against the concerned targets using the Molecular Docking Server. Our study revealed that only cilostazol has the most favorable binding interaction on Mpro (PDB ID: 6LU7) and cilostazol, iloprost, epoprostenol, prasugrel, and icosapent ethyl have a higher binding affinity on spike glycoprotein (S) (PDB ID: 6VYB) compared with recent anti-CoVID-19. Therefore, cilostazol is a promising FDA drug against COVID-19 by inhibiting both Mpro and S protein. The insights gained in this study may be useful for quick approach against COVID-19 in the future.

Antithrombotic regimen for patients with cardiac indication for dual antiplatelet therapy and anticoagulation: a meta-analysis of randomized trials.

OBJECTIVES: The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens. METHODS: Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis. RESULTS: Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26). CONCLUSION: Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.

Anticoagulantes na prática cirúrgica dermatológica / Anticoagulants in dermatological surgical practice

INTRODUÇÃO: Nas últimas décadas, o uso de anticoagulantes vem se tornando mais frequente na população e em faixas etárias mais jovens.OBJETIVO: O objetivo desse artigo é abordar o risco das medicações anticoagulantes mais utilizadas em cirurgia dermatológica.MÉTODOS: Foi realizada revisão das medicações anticoagulantes mais utilizadas.RESULTADOS: A consulta pré-cirúrgica realizada adequadamente, com ênfase ao histórico clínico do paciente (incluindo função renal nos casos de uso dos novos anticoagulantes orais), a localização anatômica abordada e a exata programação do tratamento cirúrgico são essenciais para um desfecho adequado.CONCLUSÕES: A utilização de medicações anticoagulantes é cada vez mais frequente na prática médica. Em pacientes recebendo medicações anticoagulantes é essencial a estrita adesão às boas práticas cirúrgicas, com especial atenção à hemostasia adequada do campo cirúrgico, aos curativos adequados e compressivos e aos cuidados pós-operatórios, sendo o paciente devidamente informado sobre os maiores riscos aos quais está sujeito(AU).

Introduction: In the last decades, anticoagulants have become more frequent in the population and younger age groups. Objective: This article aims to address the risk of the most used anticoagulant medications in dermatological surgeries. Methods: We reviewed the most common anticoagulant medications. Results: The pre-surgical consultation performed correctly, emphasizing the patient's clinical history (including renal function in cases of use of new oral anticoagulants), the anatomical site addressed, and the surgical treatment schedule is essential for a satisfactory outcome. Conclusions: The use of anticoagulant medications is increasingly common in medical practice. In patients receiving anticoagulant medications, strict adherence to good surgical practices is essential. Special attention to adequate hemostasis of the surgical field, adequate and compressive dressings and postoperative care must be given. The patient should be adequately informed about the most significant risks to which he is subject(AU).

Vitamin D levels and platelet reactivity in diabetic patients receiving dual antiplatelet therapy.

BACKGROUND: Hypovitaminosis D represents an emerging cardiovascular risk factor, and especially among higher-risk subsets of patients, such as in those with diabetes mellitus. The anti-inflammatory and anti-thrombotic properties of vitamin D, in fact, could be even more beneficial among diabetics, where platelet hyperreactivity and suboptimal response to antiplatelet drugs has been associated with poorer outcomes. However, no study has so far evaluated the impact of vitamin D levels on platelet reactivity and high-on treatment platelet reactivity (HRPR) among diabetic patients receiving dial antiplatelet therapy (DAPT). METHODS: Our population is represented by a consecutive cohort ofdiabetic patients treated with DAPT (ASA + clopidogrel or ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined for values above the lower limit of normality (in non-treated patients). RESULTS: We included 440 patients, that were divided according to quartiles values of vitamin D (< 9.4; 9.4-15.59; 15.6-21.64; ≥ 21.65 ng/ml). Among them, 31 were excluded as chronically treated with vitamin D supplementation. Lower vitamin D quartiles were associated with more advanced age (p = 0.01), female gender (p = 0.04), renal failure (p = 0.005), history of previous MI (p = 0.01), CABG and use of diuretics (p = 0.003), severe coronary disease (p = 0.002), but lower ejection fraction (p = 0.001), treatment with statins (p = 0.04) and new ADP-antagonists (p = 0.002). Vitamin D levels related with higher HbA1c (p = 0.001), cholesterol (p = 0.02) and creatinine (p = 0.004) and lower hemoglobin (p = 0.004). The prevalence of HRPR with ASA was low and not related to vitamin D quartiles (3.4% vs 2.7% vs 1.8% vs 2.1%, p = 0.44; adjusted OR[95%CI] = 1.16[0.60-2.26], p = 0.67). The prevalence of HRPR for ADP antagonists was associated to hypovitaminosis D (40.2% vs 29.1% vs 29.4% vs 25.5%, p = 0.03; (adjusted OR[95%CI] = 1.76[1.04-2.98], p = 0.036for I vs II-IV quartile). The impact of vitamin D quartiles, was significant only in patients on new ADP antagonists (n = 225, of whom 81 on prasugrel 5 mg; p = 0.03; adjusted OR[95%CI] = 3.12[1.34-7.49], p = 0.009) but not with clopidogrel (p = 0.85, adjusted OR[95%CI] = 1.05[0.49-2.24], p = 0.89). CONCLUSIONS: Among diabetic patients receiving dual antiplatelet therapy for an acute coronary syndrome or elective percutaneous coronary intervention, severe vitamin D deficiency is associated with a higher ADP-mediated platelet reactivity and rate of HRPR, and especially for new ADP-antagonists over clopidogrel.

Comparative Effectiveness and Safety Analysis of Dual Antiplatelet Therapies Within an Integrated Delivery System.

BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes. OBJECTIVE: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding. RESULTS: A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis. CONCLUSIONS: Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.

CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis.

PURPOSE: This study aimed to examine the cost-effectiveness of CYP2C19 loss-of-function and gain-of-function allele guided (LOF/GOF-guided) antiplatelet therapy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: A life-long decision-analytic model was designed to simulate outcomes of three strategies: universal clopidogrel (75 mg daily), universal alternative P2Y12 inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12 inhibitor, wild-type patients receiving clopidogrel). Model outcomes included clinical event rates, quality-adjusted life-years (QALYs) gained and direct medical costs from perspective of US healthcare provider. RESULTS: Base-case analysis found nonfatal myocardial infarction (5.62%) and stent thrombosis (1.2%) to be the lowest in universal alternative P2Y12 inhibitor arm, whereas nonfatal stroke (0.72%), cardiovascular death (2.42%), and major bleeding (2.73%) were lowest in LOF/GOF-guided group. LOF/GOF-guided arm gained the highest QALYs (7.5301 QALYs) at lowest life-long cost (USD 76,450). One-way sensitivity analysis showed base-case results were subject to the hazard ratio of cardiovascular death in carriers versus non-carriers of LOF allele and hazard ratio of cardiovascular death in non-carriers of LOF allele versus general patients. In probabilistic sensitivity analysis of 10,000 Monte Carlo simulations, LOF/GOF-guided therapy, universal alternative P2Y12 inhibitor, and universal clopidogrel were the preferred strategy (willingness-to-pay threshold = 50,000 USD/QALY) in 99.07%, 0.04%, and 0.89% of time, respectively. CONCLUSIONS: Using both CYP2C19 GOF and LOF alleles to select antiplatelet therapy appears to be the preferred antiplatelet strategy over universal clopidogrel and universal alternative P2Y12 inhibitor therapy for ACS patients with PCI.