Since the onset of the COVID‐19 pandemic, a substantial proportion of COVID‐19 patients had documented thrombotic complications and ischemic stroke. Several mechanisms related to immune‐mediated thrombosis, the renin angiotensin system and the effect of SARS‐CoV‐2 in cardiac and brain tissue may contribute to the pathogenesis of ischemic stroke in patients with COVID‐19. Simultaneously, significant strains on global healthcare delivery, including ischemic stroke management, have made treatment of stroke in the setting of COVID‐19 particularly challenging. In this review, we summarize the current knowledge on epidemiology, clinical manifestation, and pathophysiology of ischemic stroke in patients with COVID‐19 to bridge the gap from bench to bedside and clinical practice during the most challenging global health crisis of the last decades.

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 ( n = 16) or placebo ( n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101–treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug’s inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

Background and aims: To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. Methods: English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Results: Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60–0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70–0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of “the lower the better” hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Conclusions: Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.

Aim of the study: The increase in physician‐reported diabetes following rosuvastatin treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin study has raised concerns whether this statin exerts a detrimental effect on glucose metabolism. We assessed the effect of rosuvastatin treatment across dose range on glucose homeostasis in hyperlipidaemic patients with impaired fasting glucose (IFG), who are at high risk to develop diabetes mellitus. Methods: The medical records of 72 hypelipidaemic patients with IFG on rosuvastatin 10 (RSV10 group), 20 (RSV20 group) and 40 mg/day (RSV40 group) were reviewed. The median follow up was 12.4 weeks. At the first visit, prior to rosuvastatin prescription and at the latest visit, serum lipid profile and indices of glucose metabolism, including fasting glucose, insulin and HOmeostasis Model Assessment (HOMA_IR) index levels, were assessed. Results: Rosuvastatin treatment improved lipid profile and was associated with a dose‐dependent significant increase in HOMA_IR values by 25.4%, 32.3% and 44.8% at the dose of 10, 20 and 40 mg/day (p < 0.01 for all, p < 0.05 for the comparison between groups), respectively, mirrored by correspondent increase in plasma insulin levels [by 21.7%, 25.7% and 46.2% in the RSV10, RSV20 and RSV40 group (p < 0.001 for all) respectively]. Baseline HOMA_IR levels was the most important contributor (R² = 68.1%, p < 0.001), followed by the dose of rosuvastatin treatment (R² = 23.7%, p < 0.01), in a model that explained 91.8% of the variability in HOMA_IR increase. Conclusion: In patients with IFG and hyperlipidaemia, rosuvastatin treatment was associated with a dose‐dependent increase in insulin resistance.