这一观点探讨了用于治疗类风湿关节炎 (RA) 和其他风湿病的 Janus 激酶抑制剂 (JAK-Is) 的安全性问题。越来越多的证据表明，JAK-Is 可能会增加静脉血栓栓塞 (VTE)，尤其是肺栓塞的风险。这一事实促使欧洲药品管理局建议 65 岁以上的患者、吸烟者以及有心血管问题或癌症风险的患者谨慎使用这些药物。本文分析了 VTE 风险与 RA 之间关联的证据，以及不同的 JAK-Is 是否会带来不同的风险。它还探讨了 VTE、脂质和 JAK 抑制之间的联系，指出 JAK-Is 可以改变 HDL 和 LDL 水平。另一方面，一些证据表明，更严格的低密度脂蛋白胆固醇控制可以降低静脉血栓栓塞风险，特别是肺栓塞风险。此外，试验数据显示，很少有人关注风湿病患者这一主要心血管和静脉血栓栓塞危险因素的治疗。尽管脂质悖论理论强调 RA 患者 LDL 胆固醇与心血管风险之间的 U 形关系，但临床相关 LDL 胆固醇不受控制的水平仍然与心血管和 VTE 风险密切相关。总之，高效他汀类药物可以帮助控制风湿病患者接受 JAK-Is 治疗时增加的心血管和 VTE 风险，同时不会剥夺他们的最佳治疗选择，此外还可以降低与该疾病相关的固有风险。© 2023 . 作者获得意大利国际医学协会 (SIMI) 的独家许可。

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).