Antithrombotic therapies (ATT) play a pivotal role in the management of cardiovascular diseases, aiming to prevent ischemic events while maintaining a delicate balance with the patient\'s bleeding risk. Typically, ATT can be classified into antiplatelet and anticoagulant therapies. Their application spans a broad spectrum of cardiovascular conditions, ranging from ischemic heart disease to atrial fibrillation, encompassing venous thromboembolisms and innovative structural interventional cardiology procedures. The global burden of cardiovascular diseases is steadily increasing, often giving rise to overlapping clinical presentations. Accordingly, the adoption of combined pharmacological approaches becomes imperative, potentially disrupting the delicate equilibrium between ischemic and bleeding risk, thus leading to nuanced pharmacotherapeutic pathways. In this context, contemporary investigations strive to identify a convergence point that optimizes the duration of medical therapy while addressing the need for antithrombotic effects, especially in the context of ischemic heart disease. This review aims to comprehensively revisit the main antithrombotic strategies in cardiovascular diseases, with the intention of enhancing a systematic approach which is key for the effective clinical management of these patients. Also, the review will examine the most impactful studies that have established the groundwork for current scientific evidence, with acknowledgement of special populations. Finally, we will cast a gaze into the future of this dynamic and evolving research field, exploring forthcoming perspectives and advancements.

Cancer-associated thrombosis (CAT) is a devastating complication of cancer that can significantly impact a patient\'s health and life. The incidence of CAT is approximately 20%, and 1 in 5 cancer patients will develop CAT annually. Indeed, CAT can promote pulmonary embolism and deep vein thrombosis, leading to increased morbidity and mortality that dramatically impact survival. CAT can also provoke delay or discontinuation of anticancer treatment, which may result in a lack of treatment efficacy and high costs for patients, institutions, and society. Current guidelines advocate direct oral anticoagulants (DOACs) as the first-line anticoagulant option in CAT. Compared to low-molecular-weight-heparins (LMWHs), DOACs are advantageous in that they typically have an oral route of administration, do not require laboratory monitoring, and have a more predictable anticoagulant effect. However, in patients with thrombocytopenia, renal failure, or those receiving anticancer regimens with potential for drug-drug interactions, LMWH is still the mainstay of care. The main limitation of current anticoagulant agents is related to bleeding risk (BR), both for DOACs and LMWHs. Specifically, DOACs have been associated with high BR in gastrointestinal and genitourinary cancers. In this challenging scenario, abelacimab, an anti-factor XI agent, could represent a viable option in the management of CAT due to its \"hemostasis sparing\" effect. The safe profile of abelacimab could be useful in patients with active malignancy and CAT, as long-term anticoagulant therapy is often required. Two ongoing international phase III trials (Aster and Magnolia) compare abelacimab with the standard of care (i.e., apixaban in patients with CAT and dalteparin in those with CAT and high BR, respectively). Abelacimab is a new and attractive anticoagulant for the management of CAT, especially in the insidious and critical scenario of active cancer patients with venous thromboembolism and high BR. The aim of this narrative review is to discuss the updated evidence on the performance of DOACs and LMWHs in the treatment of CAT and to focus on the potential role of abelacimab in CAT and its promising associated clinical trials.

OBJECTIVE: Polyvascular disease has a significant global burden and is associated with increased risk of major adverse cardiac events with each additional vascular territory involved. The purpose of this review is to highlight the risk factors, associated outcomes, emerging genetic markers, and evidence for screening and treatment of polyvascular disease.
RESULTS: Polyvascular disease is the presence of atherosclerosis in two or more vascular beds. It has a significant global burden, with a prevalence of 30-70% in patients with known atherosclerosis. Patients with polyvascular disease experience elevated rates of cardiovascular death, myocardial infarction and stroke, especially among high-risk subgroups like those with type 2 diabetes mellitus and there is a step-wise increased risk of adverse outcomes with each additional vascular territory involved. Genetic analyses demonstrate that some individuals may carry a genetic predisposition, while others exhibit higher levels of atherogenic lipoproteins and inflammatory markers. Routine screening for asymptomatic disease is not currently recommended by major cardiovascular societies unless patients are high-risk. While there are no established protocols for escalating treatment, existing guidelines advocate for lipid-lowering therapy. Additionally, recent studies have demonstrated benefit from antithrombotic agents, such as P2Y12 inhibitors and low-dose anticoagulation, but the optimal timing and dosage of these agents has not been established, and the ischemic benefit must be balanced against the increased risk of bleeding in the polyvascular population. Due to the high prevalence and risks associated with polyvascular disease, early identification and treatment intensification are crucial to reduce disease progression. Future research is needed to develop screening protocols and determine the optimal timing and dosing of therapy to prevent ischemic events.

The growing geriatric population presenting with coronary artery disease poses a primary challenge for healthcare services. This is a highly heterogeneous population, often underrepresented in studies and clinical trials, with distinctive characteristics that render them particularly vulnerable to standard management/approaches. In this review, we aim to summarize the available evidence on the treatment of acute coronary syndrome in the elderly. Additionally, we contextualize frailty, comorbidity, sarcopenia, and cognitive impairment, common in these patients, within the realm of coronary artery disease, proposing strategies for each case that may assist in therapeutic approaches.

OBJECTIVE: Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone.
METHODS: MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model.
RESULTS: Forty-two studies were included. In an analysis of 15 RCTs and 19 observational studies evaluating OAC plus aspirin versus OAC alone, a significant difference in the risk of bleeding was observed in the combination groups, with an odds ratio [OR] of, 1.36 (95% CI, 1.15-1.59) for RCTs and an OR of 1.42 (95% CI-, 1.09-1.87) for observational studies. When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75).
CONCLUSIONS: The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.

Transcatheter structural heart interventions have drastically evolved over the past 2 decades. However, most catheterization procedures require the deployment of devices in the body; therefore, the adhesion of thrombi to those devices is a major problem, resulting in the requirement of a period of postprocedural antithrombotic regimen. However, in recent years, bleeding associated with these antithrombotic therapies has also become a major concern, attracting the attention of investigators. This is complicated by the fact that patients at high thrombotic risk are also at high bleeding risk, making the issue of administrating antithrombotic therapy challenging. The objective of this review was to identify the important issues and summarize the current status of postoperative antithrombotic therapy and assessment of the bleeding risk following transcatheter structural heart interventions such as transcatheter aortic valve replacement, transcatheter edge-to-edge repair, and transcatheter left atrial appendage occlusion.

Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor, is the cornerstone of post-percutaneous coronary intervention treatment to prevent stent thrombosis and reduce the risk of adverse cardiovascular events. The selection of an optimal DAPT regimen, considering the interplay of various antiplatelet agents, patient profiles, and procedural characteristics, remains an evolving challenge. Traditionally, a standard duration of 12 months has been recommended for DAPT in most patients. While contemporary guidelines provide general frameworks, DAPT modulation with longer or shorter treatment courses followed by aspirin or P2Y12 inhibitor monotherapy are evolving towards an individualized strategy to optimize the balance between efficacy and safety. This review comprehensively examines the current landscape of DAPT strategies after coronary stenting, with a focus on emerging evidence for treatment individualization.

This is a retrospective study of patients admitted to Jackson Hospital, Montgomery, Alabama, with a diagnosis of COVID-19 from January 1, 2021, to February 15, 2022. The independent variables used in the models were patient sex, age, race, BMI category, daily D-dimer categories, categories of anticoagulation doses, bleeding episodes, and vaccination status. The three different categories of anticoagulation doses were considered for the purpose of the study which were Enoxaparin 40 mg daily vs Enoxaparin 80 mg daily vs Enoxaparin 1 mg/kg or equivalent daily. The study reviewed a total of 100 hospitalized patients. Intermediate-dose anticoagulation was found to be the optimal dose as only 14% patients died compared to a 36 and 50% death rate among those treated with low-dose and high-dose anticoagulation, respectively. The multivariate linear regression model predicting patient oxygen requirements revealed D-dimer and bleeding status to be statistically significant predictors with a p value of <0.01. For the patients who had a D-dimer value ≥2 µg/mL, the oxygenation requirement was predicted to be 31 L higher than those with a D-dimer <2 µg/mL (99% CI; p < 0.01). When mean D-dimer and corresponding oxygen requirements were calculated per hospitalization days category, the D-dimer levels and oxygen requirements were noted to follow the same trends indicating that both values tended to increase and decrease simultaneously. The study concludes daily D-dimer trends can predict COVID-19 patient survival or daily oxygen requirements indicating that D-dimer can be the miracle molecule for COVID-19 prognosis.

Endoscopic sinus surgery (ESS) is the gold standard for the management of chronic rhinosinusitis, nasal polyposis, and other pathology involving paranasal sinus as tumors. Intraoperative bleeding during ESS can be challenging due to the narrow sinonasal surgical field, single working hand, and the use of endoscopic instruments, which may affect hemostasis. There is a role for the type of anesthesia technique used for intraoperative bleeding control. Total intravenous anesthesia (TIVA) and inhalational anesthesia (IA) are some of the techniques available for anesthetic purposes. While both techniques have their advantages and disadvantages, there is a need to compare their efficacy and safety to determine which technique is more appropriate for ESS. In this review, our main focus was to summarize the current evidence about the different techniques of anesthesia used during ESS. A systematic review of the PubMed/MEDLINE database was performed using specific English terms related to TIVA and IA/volatile anesthesia used during ESS. A total of 548 publications were considered. Among these, 329 studies did not fulfill the criteria for inclusion in the systematic review, resulting in the inclusion of only 132 publications: 13 systematic reviews, 32 reviews, 92 randomized controlled trials, and 13 meta-analyses. The state of the art favors the use of TIVA during ESS due to its significant improvement in the intraoperative surgical field with less blood loss. Further studies aim to compare long-term nasal status with objective tools, ideally in similar pathology with the same surgeon.

OBJECTIVE: To summarize the totality of evidence validating the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, ascertaining its aggregate discrimination and validation power in multiple population subsets.
RESULTS: We searched electronic databases from 2017 (PRECISE-DAPT proposal) up to March 2023 for studies that reported the occurrence of out-of-hospital bleedings according to the PRECISE-DAPT score in patients receiving DAPT following percutaneous coronary intervention (PCI). Pooled odds ratios (OR) with 95% confidence interval (CI) were used as summary statistics and were calculated using a random-effects model. Primary and secondary endpoints were the occurrence of any and major bleeding, respectively. A total of 21 studies and 67 283 patients were included; 24.7% of patients (N = 16 603) were at high bleeding risk (PRECISE-DAPT score ≥25), and when compared to those at low bleeding risk, they experienced a significantly higher rate of any out-of-hospital bleeding (OR: 2.71; 95% CI: 2.24-3.29; P-value <0.001) and major bleedings (OR: 3.51; 95% CI: 2.71-4.55; P-value <0.001). Pooling data on c-stat whenever available, the PRECISE-DAPT score showed a moderate discriminative power in predicting major bleeding events at 1 year (pooled c-stat: 0.71; 95% CI: 0.64-0.77).
CONCLUSIONS: This systematic review and meta-analysis confirms the external validity of the PRECISE-DAPT score in predicting out-of-hospital bleeding outcomes in patients on DAPT following PCI. The moderate discriminative ability highlights the need for future improved risk prediction tools in the field.