Department of Medicine and Ageing Sciences, "G. d'Annunzio" University of Chieti-Pescara, Italy (N.P.).
Department of Internal Medicine, Medical Center, S.C. Medicina Generale 1, Ospedale di Circolo and Fondazione Macchi, ASST Sette Laghi Varese, Italy (A.B.).
Arterioscler Thromb Vasc Biol. 2024 Dec;44(12):2371-2395. doi: 10.1161/ATVBAHA.124.319980. Epub 2024 Oct 10.
Cardiovascular disease (CVD) remains a major health burden despite significant therapeutic advances accomplished over the last decades. It is widely and increasingly recognized that systemic inflammation not only represents a major cardiovascular risk and prognostic factor but also plays key pathogenic roles in CVD development and progression. Despite compelling preclinical evidence suggesting large potential of anti-inflammatory pharmacological interventions across numerous CVDs, clinical translation remains incomplete, mainly due to (1) yet undefined molecular signaling; (2) challenges of safety and efficacy profile of anti-inflammatory drugs; and (3) difficulties in identifying optimal patient candidates and responders to anti-inflammatory therapeutics, as well as optimal therapeutic windows. Randomized controlled trials demonstrated the safety/efficacy of canakinumab and colchicine in secondary cardiovascular prevention, providing confirmation for the involvement of a specific inflammatory pathway (NLRP3 [NACHT, LRR, and PYD domain-containing protein 3] inflammasome/IL [interleukin]-1β) in atherosclerotic CVD. Colchicine was recently approved by the US Food and Drug Administration for this indication. Diverse anti-inflammatory drugs targeting distinct inflammatory pathways are widely used for the management of other CVDs including myocarditis and pericarditis. Ongoing research efforts are directed to implementing anti-inflammatory therapeutic strategies across a growing number of CVDs, through repurposing of available anti-inflammatory drugs and development of novel anti-inflammatory compounds, which are herein concisely discussed. This review also summarizes the main characteristics and findings of completed and upcoming randomized controlled trials directly targeting inflammation in CVDs, and discusses major challenges and future perspectives in the exciting and constantly expanding landscape of cardioimmunology.
尽管在过去几十年中取得了重大的治疗进展，但心血管疾病（CVD）仍然是一个主要的健康负担。人们广泛且日益认识到，系统性炎症不仅是一个主要的心血管风险和预后因素，而且在 CVD 的发展和进展中也起着关键的致病作用。尽管有大量令人信服的临床前证据表明，抗炎药理学干预在多种 CVD 中具有巨大的潜力，但临床转化仍未完成，主要原因有：（1）尚未明确的分子信号；（2）抗炎药物的安全性和疗效特征的挑战；（3）识别抗炎治疗的最佳患者候选者和反应者以及最佳治疗窗口的困难。随机对照试验证明了卡那单抗和秋水仙碱在二级心血管预防中的安全性/疗效，为特定炎症途径（NLRP3 [NACHT、LRR 和 PYD 结构域蛋白 3] 炎性体/IL [白细胞介素]-1β）在动脉粥样硬化性 CVD 中的参与提供了确认。秋水仙碱最近已被美国食品和药物管理局批准用于该适应症。针对不同炎症途径的多种抗炎药物广泛用于治疗其他 CVD，包括心肌炎和心包炎。目前正在努力通过重新利用现有的抗炎药物和开发新型抗炎化合物，在越来越多的 CVD 中实施抗炎治疗策略，本文对此进行了简要讨论。这篇综述还总结了直接针对 CVD 中炎症的已完成和即将进行的随机对照试验的主要特征和发现，并讨论了在令人兴奋且不断扩大的心脏免疫学领域中存在的主要挑战和未来展望。
