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Introduction: Antithrombotic therapy field is undergoing rapid and significant changes during the past decade. In addition to new therapeutic strategies with existing targets, investigators are exploring the potential use of new targets to address unmet needs to treat patients with arterial diseases., Areas Covered: We aim to provide an update on and a comprehensive review of the antithrombic agents that are being explored in patients with arterial diseases. We discuss latest developments with respect to upstream antiplatelet agents, and collagen and thrombin pathway inhibitors. We searched PubMed databases for English language articles using keywords: antiplatelet agents, thrombin pathway inhibitors, collagen receptors, arterial disease., Expert Opinion: Despite implementation of potent P2Y 12 inhibitors, there are numerous unmet needs in the treatment of arterial diseases including ceiling effect of currently available antiplatelet agents along with and an elevated risk of bleeding. The latter observations encouraged investigators to explore new targets that can attenuate the generation of platelet-fibrin clot formation and subsequent ischemic event occurrences with minimal effect on bleeding. These targets include collagen receptors on platelets and thrombin generation including FXa, FXIa, and FXIIa. In addition, investigators are studying novel antiplatelet agents/strategies to facilitate upstream therapy in high-risk patients.

Background and Aims: In the association between hypercholesterolemia (HC) and thrombotic risk platelet hyper-reactivity plays an important role. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce plasma LDL-cholesterol merges as effective therapeutic strategy to prevent cardiovascular (CV) events. Aim of this study was to verify whether a treatment up to 12 months with the monoclonal antibodies (mAbs) anti-PCSK9 influences platelet function in primary HC., Methods and Results: In patients affected by primary HC (n = 24), all on background of statin and 17 on acetyl salicylic acid (ASA), platelet function parameters were evaluated at baseline up to 12 months of treatment with the mAb anti-PCSK9 alirocumab or evolocumab. From baseline, the treatment with anti-PCSK9 mAbs: i) in ASA HC patients, significantly decreased platelet aggregation detected in platelet-rich plasma by light transmission aggregometry and in whole blood Platelet Function Analyzer-100 assay; ii) in all HC patients, significantly decreased platelet membrane expression of CD62P and plasma levels of the in vivo platelet activation markers soluble CD40 Ligand, Platelet Factor-4, and soluble P-Selectin. Furthermore, CD62P expression, and sP-Selectin, PF-4, sCD40L levels significantly correlated with serum PCSK9., Conclusion: Besides markedly lowering LDL-c levels, our results suggest that HC patients benefit from anti-PCSK9 mAb treatment also for reducing platelet reactivity and increasing platelet sensitivity to the inhibitory effects of aspirin. These effects on platelets could play a role in the reduction of CV event incidence in patients treated with PCSK9 inhibitors., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The fecal immunochemical test (FIT) is the tool most frequently used for colorectal cancer (CRC) screening worldwide. It is unclear how the use of aspirin and oral anticoagulants in the screening population affects the diagnostic performance of FIT., Methods: We performed a cross-sectional study in an ongoing CRC screening trial in Norway. Participants aged 50-74 years with a positive result from an FIT (>15 μg hemoglobin/g feces) and subsequent colonoscopy (reference standard) were included. Those who used regular aspirin, warfarin, or direct-acting oral anticoagulants (DOACs) were defined as users. Non-users were matched according to age, sex, screening center, and screening round. The primary outcomes were the positive predictive value (PPV) for CRC and advanced adenoma., Results: Among 4908 eligible participants, 1008 used aspirin, 147 used warfarin, 212 used DOACs, and 3541 were non-users. CRCs were found in 234 individuals and advanced adenomas in 1305 individuals. The PPV for CRC was 3.8% for aspirin users vs 6.4% for matched non-users (P = .006), The PPV for advanced adenoma in aspirin users was 27.2% vs 32.6% for matched non-users (P = .011). For DOAC, the PPV for CRC was 0.9% in users vs 6.8% in matched non-users (P = .001). The PPV for advanced adenoma in DOAC users was 20.5% vs 32.4% in matched non-users (P = .002). There was no significant difference in PPV for CRC or advanced adenoma in warfarin users compared to non-users., Conclusions: In a large screening cohort in Norway, regular use of aspirin and particularly DOACs, were associated with lower PPV of FIT for detection of CRCs and advanced adenomas. ClinicalTrials.gov ID NCT01538550., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: In the SMILE-4 study, zofenopril + acetyl salicylic acid (ASA) was more effective than ramipril + ASA on 1-year prevention of major cardiovascular events (MACE) in patients with acute myocardial infarction complicated by left ventricular dysfunction. In this retrospective analysis, we evaluated drug efficacy in subgroups of patients, according to a history of diabetes mellitus., Methods: The primary study endpoint was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Diabetes was defined according to medical history (previous known diagnosis)., Results: A total of 562 of 693 (81.0%) patients were classified as nondiabetics and 131 (18.9%) as diabetics. The adjusted rate of MACE was lower under zofenopril than under ramipril in both nondiabetics [27.9% vs. 34.9% ramipril; odds ratio, OR and 95% confidence interval: 0.55 (0.35, 0.86)] and diabetics [30.9% vs. 41.3%; 0.56 (0.18, 1.73)], although the difference was statistically significant only for the nondiabetic group (P = 0.013). Zofenopril was superior to ramipril as regards to the primary study endpoint in the subgroup of 157 patients with uncontrolled blood glucose (≥ 126 mg/dL), regardless of a previous diagnosis of diabetes [0.31 (0.10, 0.90), P = 0.030]. Zofenopril significantly reduced the risk of hospitalization for cardiovascular causes in both nondiabetics [0.64 (0.43, 0.96), P = 0.030] and diabetics [0.38 (0.15, 0.95), P = 0.038], whereas it was not better than ramipril in terms of prevention of cardiovascular deaths., Conclusions: This retrospective analysis of the SMILE-4 study confirmed the good efficacy of zofenopril plus ASA in the prevention of long-term MACE also in the subgroup of patients with diabetes mellitus., (© 2016 John Wiley & Sons Ltd.)

Objective: To evaluate the safety of continuing acetyl salicylic acid (ASA) in patients undergoing brain tumor resection. Many patients are on antiplatelet agents that are withheld before elective neurosurgical procedures to reduce bleeding risk. Cessation of ASA in patients with cardiovascular disease is associated with a known increased risk of thrombotic events, especially in patients with coronary stents., Methods: The medical records of patients who underwent surgical resection of a brain tumor at the University of Florida from 2010 to 2014 were evaluated. The patients were separated into groups based on preoperative ASA use and whether or not it was stopped before surgery. Patients were evaluated for thrombotic complications, postoperative hemorrhage, estimated blood loss, length of hospital stay, and discharge disposition., Results: Of the 452 patients analyzed, 368 patients were not on chronic ASA therapy, 55 patients had their ASA discontinued before surgery, and 28 patients were continued on ASA perioperatively. The patients on preoperative ASA were comparable on all collected demographic variables. There were no statistical differences detected between the groups for outcomes including bleeding complications, need for reoperation, or thrombotic complications., Conclusions: In this analysis, perioperative low dose ASA use was not associated with increased risk of perioperative complications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background The optimal vascular access for chronic hemodialysis is the arteriovenous fistula (AVF). Several studies suggest a role for antiplatelet agents in the prevention of early AVF failure. Aim of the study This trial was conducted to assess the efficacy and safety of clopidogrel versus acetyl salicylic acid in hemodialysis patients. Patients and Methods A total of 50 patients received 75 mg/day of clopidogrel, 50 patients received 150 mg/day of acetyl salicylic acid, and 50 patients served as the control group. The treatment was initiated 7-10 days before the surgery and continued up to 6 weeks postoperatively; thereafter, patients were monitored for 6 months. Results The primary outcome was AVF failure 8 weeks after fistula creation. The primary AVF failures at 2 months were 32.5% in the acetyl salicylic acid group and 6.6% in the clopidogrel group. First hemodialysis from newly created AVF in the clopidogrel group was significantly more successful than that in the acetyl salicylic acid group. No life-threatening adverse event or severe bleeding was recorded in both groups. Conclusion Clopidogrel seems to be effective and safe compared with acetyl salicylic acid in the prevention of primary AVF failure in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The administration of antiplatelet agents versus anticoagulation after bioprosthetic aortic valve replacement (AVR) remains controversial. This study examined the safety and efficacy of anticoagulation with a vitamin-K antagonist (VKA) versus low-dose acetyl salicylic acid (ASA), up to 6months after bioprosthetic AVR. Methods: The ACTION Registry prospectively collected data at 47 medical centers in Europe, Canada and India. The investigators were free to prescribe the postoperative antithrombotic regimen of their choice. Between January 2006 and June 2009, 1118 patients underwent AVR alone or combined with coronary artery bypass graft (CABG), of whom 500 received a VKA and 618 received ASA. Results: Patients who received VKA had a higher prevalence of peripheral vascular disease, chronic renal insufficiency and coronary artery disease. At 180days, 14 anticoagulated patients (2.8%) suffered a thromboembolism (TE) versus 9 patients (1.5%) treated with ASA (P =0.12) and 18 anticoagulated patients (3.6%) suffered major bleeding (MB) versus 8 patients (1.3%) in the ASA group (P =0.01). MB or TE occurred in 31 patients (6%) treated with VKA versus 17 patients (2.8%) treated with ASA (P =0.003). By multiple variable analysis, preoperative cerebrovascular accident and peripheral vascular disease were strong predictors of postoperative TE, MB or both, in patients treated with VKA, though not in patients treated with ASA. Conclusions: Compared with ASA, treatment with VKA was associated with higher morbidity within 6months after bioprosthetic AVR, suggesting that, particularly after concomitant CABG surgery, recipients of bioprosthetic AVR should receive prophylactic ASA instead of VKA. [Copyright &y& Elsevier]

An acetyl salicylic acid-caffeine complex was prepared and evaluated for the potential use in rectal administration. The results revealed the formation of a complex between acetyl salicylic acid and caffeine in a 1:1 molar ratio by a charge transfer mechanism. The effects of acetyl salicylic acid and complex on the rectal tissues showed destruction in the mucosal epithelium in case of acetyl salicylic acid; however, no change in the rectal tissues was noticed upon the administration of the complex. The effect of suppository bases on the release of the complex was studied using Witepsol H15 as fatty base and polyethylene glycols (PEG) 1000 and 4000 as a water soluble suppository base. The release profiles of acetyl salicylic acid and the complex were faster from PEG than from that of Witepsol H15. The percent release for the complex and acetyl salicylic acid from PEG base were 45.8, and 34.9%, respectively. However, it was 8.7 and 7.8%, respectively, from Witepsol H15 fatty base. The release kinetic was found to follow the non-Fickian diffusion model for complex from the suppository bases. It was concluded that acetyl salicylic acid caffeine complex can be used safely for rectal administration. [ABSTRACT FROM AUTHOR]