Initially recognized for their role in vascular haemostasis, platelets are now understood to be critical regulators of inflammation and immune responses through complex interactions with immune cells. Key to this role is the formation of platelet–leukocyte aggregates (PLAs), with platelet–monocyte aggregates (PMAs) representing the most thoroughly studied type in cardiovascular disease. PLAs form through the binding of platelet surface P-selectin to P-selectin glycoprotein ligand on leukocytes, an early interaction that may trigger broader inflammatory cascades. Recent studies link circulating PMAs with in vivo platelet activation and elevated PMA levels in patients with high thrombogenic risk, such as those with diabetes and acute myocardial infarction. Furthermore, PMA levels correlate with disease severity and long-term cardiovascular outcomes, highlighting their potential as prognostic biomarkers for adverse cardiovascular events. Therapeutic strategies, such as antiplatelet agents and P-selectin antagonists, have demonstrated efficacy in the inhibition of PLA formation. However, the development of selective inhibitors that preserve the haemostatic and immune functions of platelets remains an unmet clinical need. Despite significant progress, the precise biological functions and underlying mechanisms of PLAs are not fully understood. This review integrates preclinical and clinical data to provide a comprehensive overview of platelet–leukocyte biology, with a focus on the prognostic role and therapeutic potential of PLAs in cardiovascular disease.

Background: Late adverse events after percutaneous coronary intervention continue to occur beyond the first year with last‐generation drug‐eluting stents (DES). The coronary bioadaptor marks a new approach with an uncaging beginning at approximately 6 months after implantation. We conducted a pairwise meta‐analysis of bioadaptor versus DES in randomised trials with complementary single‐arm 6–12 and 6–24 landmark analyses. Methods: The systematic review and meta‐analysis was conducted according to PRISMA 2020 Guidelines. PubMed, Embase, CENTRAL and Google Scholar were searched for studies reporting clinical outcomes after bioadaptor implantation. The primary outcome was target‐lesion failure (TLF), a composite of cardiac death, target‐vessel myocardial infarction and target‐lesion revascularisation at 1 year. Secondary outcomes were TLF and individual components at landmark intervals 6–12 and 6–24 months. Single‐arm pooled event rates and pairwise comparisons were estimated using generalised linear mixed‐effects models. Results: Three randomised trials ( n = 2892; 1448 bioadaptor, 1444 DES) were included in pairwise analyses. 1‐year TLF showed no significant difference between bioadaptor and DES (OR 0.81, 95% CI 0.51–1.31, I ² = 0.0%, p = 0.3943). Likewise, individual components of TLF and device thrombosis did not differ between groups. Ten studies (1753 patients; 1900 lesions) were included in single‐arm analyses. Landmark TLF was 0.57% (95% CI 0.07–4.29; I ² = 4.6%) from 6 to 12 months and 2.01% (95% CI 0.81–4.92; I ² = 74.2%) from 6 to 24 months. Event rates for other endpoints were generally low. Conclusions: No significant differences in safety and efficacy outcomes were observed between bioadaptor and DES. Complementary single‐arm landmark analyses suggested low late event rates, but these findings should be interpreted as exploratory. Further randomised trials are warranted.

Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [−1.46–2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting.