Background: Cardiovascular diseases are predominant health conditions across the world due to their rising prevalence and association with several disorders. Inclisiran, a small interfering RNA (siRNA) therapy, lowers low density lipoproteins cholesterol (LDL-C) by targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). Its exact role in cardiovascular diseases is not fully understood.Aim: This review examines current usage of Inclisran for cardiovascular diseases.Method: A detailed search of Clinicaltrials.gov was conducted to identify relevant studies that investigated heart diseases using Inclisran. Data on study design, sample size, intervention details, and outcomes related to Inclisran were extracted and analyzed.Results: As of 30 December 2024, there were 92 clinical trials on involving inclisiran found at clinicaltrials.gov. The investigation focused on studies that used inclisiran for cardiovascular diseases and found that limited clinical trials were identified with limited interventional measures. The final number of analyzed trials was 11. The follow-up duration ranged from 270 to 1,695 days with a total of 214,176 participants with a favorable safety profile and twice-yearly dosing after initial loading dose. The collective findings from these trials demonstrated effective LDL-C and PCSK9 lowering compared to baseline measurements. Most studies focused on LDL-C lowering rather than measuring cardiovascular outcomes.Conclusion: Although the studies showed inclisiran to lower LDL-C effectively, the evidence is still limited with regards to cardiovascular outcomes data. There is a need for real world studies addressing long-term safety, adherence and cost-effectiveness and therapeutic outcomes of combination therapy.

Platelet C-type lectin-like receptor 2 (CLEC-2) is a hem-immunoreceptor tyrosine–based activation motif-containing receptor that has a critical role in venous thrombosis but minimal involvement in hemostasis. CLEC-2 can be blocked by Btk inhibitors. Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs). Patients with X-linked agammaglobulinemia (XLA) who lack Btk, however, do not bleed, suggesting selective Btk inhibition as a viable antithrombotic strategy. We assessed the effects of selective Btk inhibitors PRN1008 (rilzabrutinib) and PRN473 on platelet signaling and function mediated by CLEC-2 and glycoprotein-VI. We used healthy donors and XLA platelets to determine off-target inhibitor effects. Inferior vena cava (IVC) stenosis and Salmonella infection mouse models were used to assess antithrombotic effects of PRN473 in vivo. PRN1008 and PRN473 potently inhibited CLEC-2–mediated platelet activation to rhodocytin. No off-target inhibition of SFKs was seen. PRN1008 treatment of Btk-deficient platelets resulted in minor additional inhibition of aggregation and tyrosine phosphorylation, likely reflecting inhibition of Tec. No effect on G protein-coupled receptor-mediated platelet function was observed. PRN473 significantly reduced the number of thrombi in podoplanin-positive vessels after Salmonella infection and the presence of IVC thrombosis after vein stenosis. The potent inhibition of human platelet CLEC-2 and reduced thrombosis in in vivo models, together with the lack of off-target SFK inhibition and absence of bleeding reported in rilzabrutinib-treated patients with immune thrombocytopenia, suggest Btk inhibition as a promising antithrombotic strategy.

New antithrombotic therapies with less effect on bleeding are needed for coronary artery disease. The Btk inhibitor ibrutinib blocks atherosclerotic plaque–mediated thrombus formation. However, it is associated with increased bleeding, possibly due to non–Btk‐mediated effects. Btk‐deficient patients do not have bleeding issues, suggesting selective Btk inhibition as a promising antithrombotic strategy. To compare the antithrombotic effects of the highly selective Btk inhibitor AB‐95‐LH34 (LH34) with ibrutinib. Glycoprotein VI and G‐protein coupled receptor‐mediated platelet function and signaling were analyzed in healthy human donor platelets by lumi‐aggregometry, flow adhesion, and western blot following 1 h treatment with inhibitors in vitro. LH34 showed similar inhibition of Btk‐Y223 phosphorylation as ibrutinib, but had no off‐target inhibition of Src‐Y418 phosphorylation. Similar dose‐dependent inhibition of aggregation to atherosclerotic plaque material was observed for both. However, in response to Horm collagen, which also binds integrin α2β1, LH34 exhibited less marked inhibition than ibrutinib. Both LH34 and ibrutinib inhibited platelet adhesion and aggregation to plaque material at arterial shear. Ibrutinib demonstrated the most potent effect, with complete blockade at high concentrations. Platelet activation (P‐selectin) and procoagulant activity (phosphatidylserine exposure) in thrombi were inhibited by LH34 and completely blocked by ibrutinib at high concentrations. Furthermore, plaque‐induced thrombin generation was reduced by higher concentrations of LH34 and ibrutinib. LH34 potently inhibits atherosclerotic plaque–induced thrombus formation and procoagulant platelet activity in vitro, with less off‐target inhibition of Src than ibrutinib, suggesting it is a promising antiplatelet therapy with the potential for reduced bleeding side effects.

New antithrombotic medications with less effect on haemostasis are needed for the long-term treatment of acute coronary syndromes (ACS). The platelet receptor glycoprotein VI (GPVI) is critical in atherothrombosis, mediating platelet activation at atherosclerotic plaque. The inhibition of spleen tyrosine kinase (Syk) has been shown to block GPVI-mediated platelet function. The aim of our study was to investigate if the Syk inhibitor fostamatinib could be repurposed as an antiplatelet drug, either alone or in combination with conventional antiplatelet therapy. The effect of the active metabolite of fostamatinib (R406) was assessed on platelet activation and function induced by atherosclerotic plaque and a range of agonists in the presence and absence of the commonly used antiplatelet agents aspirin and ticagrelor. The effects were determined ex vivo using blood from healthy volunteers and aspirin- and ticagrelor-treated patients with ACS. Fostamatinib was also assessed in murine models of thrombosis. R406 mildly inhibited platelet responses induced by atherosclerotic plaque homogenate, likely due to GPVI inhibition. The anti-GPVI effects of R406 were amplified by the commonly-used antiplatelet medications aspirin and ticagrelor; however, the effects of R406 were concentration-dependent and diminished in the presence of plasma proteins, which may explain why fostamatinib did not significantly inhibit thrombosis in murine models. For the first time, we demonstrate that the Syk inhibitor R406 provides mild inhibition of platelet responses induced by atherosclerotic plaque and that this is mildly amplified by aspirin and ticagrelor.

Background: Substance abuse is a major public health issue, particularly among university students. Understanding students’ knowledge and attitudes toward substance abuse is important for designing educational and preventive strategies, helping early intervention efforts, supporting mental health services, and ensuring culturally suitable programming. Objective: This study aimed to assess university students’ knowledge and attitudes regarding substance abuse and to identify demographic and educational factors associated with these variables. Methods: A cross-sectional study was conducted among 745 university students from various academic disciplines. Data were collected using a structured questionnaire assessing knowledge and attitudes related to substance abuse. Statistical analyses included descriptive statistics, reliability analysis, correlation, and regression tests. Results: The sample included 50.5% males and 49.5% females, with the majority aged 18–21 years (58.0%). Most participants had heard of substance abuse (91.7%) and recognized its association with chronic disease (97.3%). Knowledge scores varied significantly on the basis of academic background and prior exposure to awareness programs. Attitudes toward substance abuse were mixed, with a notable proportion of students perceiving potential benefits in certain contexts. A weak, non-significant correlation was found between knowledge and attitudes (r = 0.068, p = 0.064). Conclusion: Although students showed generally good knowledge about substance abuse, variations in understanding and attitudes were obvious across demographic and educational subgroups. These findings emphasize the need for targeted, context-specific educational interventions to address misconceptions and improve preventive awareness. Future research should evaluate the long-term impact of such interventions on students’ attitudes and behaviors.

Genetic testing offers significant potential for early detection, diagnosis, personalized treatment, and preventive strategies for disability-related diseases. Pharmacies, as accessible healthcare hubs, can play a pivotal role in delivering genetic testing services. However, public acceptance and awareness remain limited, particularly in Saudi Arabia. This study aims to evaluate the public knowledge, perceptions, and acceptance of genetic testing for disability-related diseases in Saudi Arabian pharmacies. A cross-sectional survey was conducted with 475 participants recruited via convenience sampling on social media. Data were collected using a structured questionnaire assessing demographics, knowledge, perception, and acceptance of pharmacy-based genetic testing. Statistical analyses, including descriptive statistics, t -tests, ANOVA, and regression modeling, were performed. While 57.6% of participants reported being somewhat aware of genetic testing, only 9.1% considered themselves very knowledgeable. Perceived benefits included early detection (84.4%) and preventive measures (64.4%). Approximately 42.5% felt comfortable with pharmacy-based genetic testing, but concerns regarding pharmacist expertise (57.7%) and test accuracy (50.7%) were prominent barriers. Acceptance was influenced significantly by age, gender, education level, and healthcare background. Despite moderate awareness and acceptance of genetic testing services in pharmacies, significant barriers remain. Addressing public concerns, improving pharmacist training, and enhancing collaborative care models are essential for successful integration of genetic testing into pharmacy practice.