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This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAT) is recommended for all patients undergoing percutaneous coronary intervention (PCI), as it significantly reduces the ischemic risk at the cost of increasing the incidence of bleeding events. Several clinical predictive models were developed to better stratify the bleeding risk associated with DAT. This systematic review aims to perform a literature survey of both standard and emerging bleeding risk scores and report their performance on predicting hemorrhagic events, especially in the era of second-generation drug-eluting stents and more potent P2Y12 inhibitors. We searched PubMed, ScienceDirect, and Cochrane databases for full-text studies that developed or validated bleeding risk scores in adult patients undergoing PCI with subsequent DAT. The risk of bias for each study was assessed using the prediction model risk of bias assessment tool (PROBAST). Eighteen studies were included in the present systematic review. Bleeding risk scores showed a modest to good discriminatory power with c-statistic ranging from 0.49 (95% CI, 0.45–0.53) to 0.82 (95% CI, 0.80–0.85). Clinical models that predict in-hospital bleeding events had a relatively good predictive performance, with c-statistic ranging from 0.70 (95% CI, 0.67–0.72) to 0.80 (95% CI, 0.73–0.87), depending on the risk scores and major hemorrhagic event definition used. The knowledge and utilization of the current bleeding risk scores in appropriate clinical contexts could improve the prediction of bleeding events. [ABSTRACT FROM AUTHOR]