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The prevalence of chronic kidney disease (CKD) is increasing due to the aging of the population and multiplication of risk factors, such as hypertension, arteriosclerosis and obesity. Impaired renal function increases both the risk of bleeding and thrombosis. There are two groups of orally administered drugs to prevent thromboembolic events in patients with CKD who require anticoagulation: vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). Although VKAs remain the first-line treatment in patients with advanced CKD, treatment with VKAs is challenging due to difficulties in maintaining the appropriate anticoagulation level, tendency to accelerate vascular calcification and faster progression of CKD in patients treated with VKAs. On the other hand, the pleiotropic effect of DOACs, including vascular protection and anti-inflammatory properties along with comparable efficacy and safety of treatment with DOACs, compared to VKAs observed in preliminary reports encourages the use of DOACs in patients with CKD. This review summarizes the available data on the efficacy and safety of DOACs in patients with CKD and provides recommendations regarding the choice of the optimal drug and dosage depending on the CKD stage.

Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in antiviral therapy, may be justified. All these effects might be especially beneficial in patients with COVID-19, suffering from endothelial dysfunction, microvascular and macrovascular thrombosis, and cytokine storm. Here, we review the recent data regarding the pathophysiology of SARS-CoV-2 activity in host cells, proposed COVID-19 therapy, the pleiotropic activity of statins, and statins in clinical trials in respiratory infections. According to the guidelines of the European and American Cardiac Societies, in patients with cardiovascular disease or high cardiovascular risk with concomitant COVID-19 it is recommended to continue statin treatment. However, the initiation of statin therapy de novo in COVID-19 treatment should only be done as part of a clinical trial.

The reduction of circulating low-density lipoprotein-cholesterol (LDL-C) is a primary target in cardiovascular risk reduction due to its well-established benefits in terms of decreased mortality. Despite the use of statin therapy, 10%–20% of high- and very-high-risk patients do not reach their LDL-C targets. There is an urgent need for improved strategies to manage dyslipidemia, especially among patients with homozygous familial hypercholesterolemia, but also in patients with established cardiovascular disease who fail to achieve LDL goals despite combined statin, ezetimibe, and PCSK9 inhibitor (PCSK9i) therapy. Inclisiran is a disruptive, first-in-class small interfering RNA (siRNA)-based therapeutic developed for the treatment of hypercholesterolemia that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) synthesis, thereby upregulating the number of LDL receptors on the hepatocytes, thus lowering the plasma LDL-C concentration. Inclisiran decreases the LDL-C levels by over 50% with one dose every 6 months, making it a simple and well-tolerated treatment strategy. In this review, we summarize the general information regarding (i) the role of LDL-C in atherosclerotic cardiovascular disease, (ii) data regarding the role of PCSK9 in cholesterol metabolism, (iii) pleiotropic effects of PCSK9, and (iv) the effects of PCSK9 silencing. In addition, we focus on inclisiran, in terms of its (i) mechanism of action, (ii) biological efficacy and safety, (iii) results from the ORION trials, (iv) benefits of its combination with statins, and (v) its potential future role in atherosclerotic cardiovascular disease.

(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prostacyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61+), activated platelets (CD61+/CD62P+), leukocytes (CD45+), and endothelial cells (CD146+) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP (p = 0.01 for both), lower concentrations of platelet and leukocyte EVs (p ≤ 0.04), delayed thrombus formation (p ≤ 0.003), and decreased thrombus size (p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs (p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP (p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size (p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.

Prostacyclin and analogues are successfully used in the treatment of pulmonary arterial hypertension (PAH) due to their vasodilatory effect on pulmonary arteries. Besides vasodilatory effect, prostacyclin analogues inhibit platelets, but their antiplatelet effect is not thoroughly established. The antiplatelet effect of prostacyclin analogues may be beneficial in case of increased risk of thromboembolic events, or undesirable in case of increased risk of bleeding. Since prostacyclin and analogues differ regarding their potency and form of administration, they might also inhibit platelets to a different extent. This review summarizes the recent evidence on the antiplatelet effects of prostacyclin and analogue in the treatment of PAH, this is important to consider when choosing the optimal treatment regimen in tailoring to an individual patients' needs.

Microparticles, also termed extracellular vesicles (EVs) are novel candidate markers of platelet activation and ongoing inflammation in vivo. Different subtypes of EVs are released from platelets, endothelial cells and leukocytes. Blood concentration of EV subtypes in patients with acute myocardial infarction, stroke and peripheral artery disease correlated with the severity of the disease. Accumulating data indicate that EVs may contribute to the development of atherosclerosis and its complications. Measurement of EV concentrations might become an element of minimally-invasive diagnostic tests, allowing for early diagnosis of cardiovascular disease (CVD), risk stratification and monitoring of therapy in patients with high cardiovascular risk. It also may allow to monitor the response to antiplatelet therapy with acetylsalicylic acid or P2Y12 antagonists. Isolation and detection of EVs have been recently standardized, allowing for further development of research on these promising biomarkers. EV-based tests might eventually be implemented into every-day clinical practice as well as in multicenter clinical trials.

Platelet extracellular vesicles (PEVs) are potential new biomarkers of platelet activation which may allow us to predict and/or diagnose developing coronary thrombosis before myocardial necrosis occurs. The P2Y1 and P2Y12 receptors play a key role in platelet activation and aggregation. Whereas the P2Y1 antagonists are at the preclinical stage, at present, the P2Y12 antagonists are the most effective treatment strategy to prevent stent thrombosis after percutaneous coronary intervention. Despite an increasing number of publications on PEVs, the mechanisms underlying their formation, including the role of purinergic receptors in this process, remain an active research field. Here, we outline the clinical relevance of PEVs in cardiovascular disease, summarize the role and downstream signalling of P2Y receptors in platelet activation, and discuss the available evidence regarding their role in PEV formation.