Gupta Muskaan, Smokovski Ivica, Chatzis Dimitrios G, Spring Kevin J, Mehndiratta Man Mohan, Beran Roy G, Bhaskar Sonu M M
Global Health Neurology Lab, Sydney, NSW, 2150, Australia.
UNSW Medicine and Health, University of New South Wales (UNSW), South West Sydney Clinical Campuses, Sydney, NSW, 2170, Australia.
CNS Drugs. 2025 Sep 9. doi: 10.1007/s40263-025-01222-3.
Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline. Key challenges limiting the full therapeutic potential of statins include interindividual variability in response and pharmacogenomic and biomarker-related resistance, inconsistencies across clinical guidelines, and limited central nervous system bioavailability. Innovations such as pharmacogenomic-guided therapy, pleiotropy-linked biomarkers, and advanced drug delivery systems (e.g., nanoparticle and intranasal formulations) may help overcome these barriers. Combination strategies with agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or sodium-glucose cotransporter 2 (SGLT2) inhibitors, and targeted interventions against neuroinflammatory resistance, show promise in enhancing treatment efficacy. In doing so, we propose a shift from conventional statin use to a precision medicine paradigm that can better serve AIS survivors, especially those at risk of post-stroke dementia or those living in resource-constrained settings. While such innovations, for example, genetic testing and novel delivery methods, may not yet be feasible in all contexts, particularly low-resource environments, they represent long-term goals for equity-driven innovation. Equity in access to high-intensity statins and novel therapies remains a global priority, particularly in low- and middle-income countries. Future research should prioritize personalized, biomarker-driven approaches and inclusive clinical trials to optimize statin use across diverse AIS populations. By advancing these strategies, statins can evolve from cardiovascular agents into integral components of precision neurovascular medicine, improving long-term outcomes and quality of life for stroke survivors.
急性缺血性中风（AIS）仍是全球范围内导致死亡和长期残疾的主要原因，幸存者面临中风复发、心血管事件和中风后痴呆的高风险。他汀类药物虽然因其降脂作用而被广泛使用，但也具有多效性，包括抗炎、内皮稳定和神经保护作用，这可能在AIS管理中提供额外益处。本文综合了关于他汀类药物双重作用机制的新证据，并评估了它们在降低复发率、提高生存率和减轻认知衰退方面的作用。限制他汀类药物充分发挥治疗潜力的关键挑战包括个体反应的差异、药物基因组学和生物标志物相关的耐药性、临床指南之间的不一致以及中枢神经系统生物利用度有限。药物基因组学指导治疗、多效性相关生物标志物和先进药物递送系统（如纳米颗粒和鼻内制剂）等创新可能有助于克服这些障碍。与前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂或钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂等药物的联合策略，以及针对神经炎症耐药性的靶向干预，在提高治疗效果方面显示出前景。在此过程中，我们建议从传统的他汀类药物使用转向精准医学模式，以更好地服务于AIS幸存者，特别是那些有中风后痴呆风险或生活在资源有限环境中的患者。虽然这些创新，例如基因检测和新型递送方法，在所有情况下，特别是在低资源环境中可能尚不具备可行性，但它们代表了公平驱动创新的长期目标。获得高强度他汀类药物和新型疗法的公平性仍然是全球优先事项，特别是在低收入和中等收入国家。未来的研究应优先考虑个性化、生物标志物驱动的方法和包容性临床试验，以优化不同AIS人群的他汀类药物使用。通过推进这些策略，他汀类药物可以从心血管药物演变为精准神经血管医学的重要组成部分，改善中风幸存者的长期结局和生活质量。
