Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and the formation of atherosclerotic plaques is established by solid evidence. PCSK9 inhibitors have proven to be a valuable and practical resource for lowering the LDL cholesterol of many patients in recent years. Their inhibitory effect on atherosclerosis progression seems to be driven not just by lipid metabolism modification but also by LDL-independent mechanisms. We review the effect of PCSK9 inhibitors on various mechanisms involving platelet activation, inflammation, endothelial dysfunction, and the resultant clot formation. The main effectors of PCSK9 activation of platelets are CD36 receptors, lipoprotein(a), oxidised LDL particles, tissue factor, and factor VIII. Many more molecules are under investigation, and this area of research is growing rapidly.

Platelets play crucial role in acute vascular atherosclerotic diseases, including myocardial infarction and stroke. Additionally, platelet aggregation is a key target of antiplatelet agents, forming the keystone of pharmacotherapy of various atherosclerotic cardiovascular diseases. Thromboelastography and thromboelastometry, representing currently available viscoelastic hemostatic assays (VHA), are designed as whole blood, real-time analyzers of clot formation and clot resolution. These assays could, in theory, overcome some limitations of currently available platelet function testing assays. This article reviews the current experience with the use of VHA for platelet function testing and for monitoring of the response to antiplatelet therapy.

The coronavirus SARS-CoV2 disease (COVID-19) is connected with significant morbidity and mortality (3.4%), disorders in hemostasis, including coagulopathy, activation of platelets, vascular injury, and changes in fibrinolysis, which may be responsible for an increased risk of thromboembolism. Many studies demonstrated relatively high rates of venous and arterial thrombosis related to COVID-19. The incidence of arterial thrombosis in severe/critically ill intensive care unit–admitted COVID-19 patients appears to be around 1%. There are several ways for the activation of platelets and coagulation that may lead to the formation of thrombi, so it is challenging to make a decision about optimal antithrombotic strategy in patients with COVID-19. This article reviews the current knowledge about the role of antiplatelet therapy in patients with COVID-19.

Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in the management of future long-term anticoagulation. It is not known whether tailoring the DOAC therapy to achieve optimal therapeutic drug levels could improve the clinical course of DOAC therapy. To be able to tailor the therapy, it is necessary to have a valid laboratory method for DOAC level assessment, to be aware of factors influencing DOAC levels and to have clinical options to tailor the treatment. Furthermore, the data regarding clinical efficacy/safety of tailored DOAC regimes are still lacking. This article reviews the current data on tailored direct oral anticoagulation in patients with AF.

Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called “high on-treatment platelet reactivity” or “resistance”) could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of “resistance” on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming.

Background: Impaired endothelial function has been associated with vascular complications in type 2 diabetes (T2D), but its role in T2D-related heart failure (HF) remains indeterminate. The aim of this study was to assess selected markers of endothelial function in T2D patients with acute decompensated HF. Methods: A pilot prospective study on patients with acute decompensated HF requiring in-hospital admission was carried out. The vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were assessed at admission and after decongestion. Subsequently, differences in these markers between T2D and non-diabetic (ND) patients were studied. Results: In total, 39 patients (21 with T2D and 18 ND patients) were enrolled. Twenty-eight patients presented with preserved ejection fraction (EF), and 11 presented with reduced EF. Looking at the VEGF levels in T2D patients, on admission, a median of 233.0 pg/mL (1.7–598 pg/mL) was found compared to 106.0 pg/mL (1.7–888 pg/mL) in ND individuals; the differences reached statistical significance (p = 0.04). There were no significant differences in VEGF levels after decongestion, and in VCAM-1 (2237 ± 1195 vs. 2699 ± 1093 ng/mL, p = 0.37) and ICAM-1 (596 ± 268 vs. 638 ± 437 ng/mL, p = 0.79) levels between T2D and ND patients upon admission and after decongestion. The value of EF (preserved or reduced) affected the VEGF levels upon admission. Conclusions: This study identified significantly higher VEGF levels upon admission due to acute decompensated HF in T2D patients.