Ou Zhenhong, Wang Fangchao, Chen Yunlin, Liu Xueyuan, Ran Boli, Yin Yuehui, Cui Kun
Department of Cardiology, Chongqing General Hospital of Chongqing University, Chongqing, China.
Department of Cardiology, Chongqing General Hospital, No. 118 Xingguang Avenue, Liangjiang New Area, Chongqing, 401120, China.
Cardiovasc Drugs Ther. 2024 Aug 29. doi: 10.1007/s10557-024-07622-9.
AIMS: Adding intensive low-density lipoprotein cholesterol (LDL-C)-lowering agents or colchicine to statin has been shown to result in additional cardiovascular benefits for patients with atherosclerotic cardiovascular diseases (ASCVD). We aimed to compare the efficacy and safety of these supplementary agents in patients with ASCVD receiving statin. METHODS: We performed a systematic review and frequentist network meta-analysis of randomized controlled trials. The primary efficacy endpoint was the main adverse cardiovascular event (MACE), and the secondary efficacy endpoints were myocardial infarct, stroke, coronary revascularization, cardiovascular death, and all-cause mortality, respectively. The safety endpoints were treatment discontinuation and non-cardiovascular death. We obtained estimates for efficacy outcomes and safety endpoints and presented these estimates as risk ratio (RR) with 95% confidence intervals. We ranked the comparative efficacy and safety of all drugs with P-scores. RESULTS: Seventeen trials totaling 85,823 participants treated with colchicine (5926 participants), intensive LDL-C lowering (37,854 participants) via proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, Niemann-Pick C1-like 1 protein (NPC1L1) inhibitor or ATP citrate lyase (ACL) inhibitor, or statin alone (42,043 participants) were included. Colchicine was associated with a greater reduction in the risk of MACE (RR 0.72, 0.69-0.91), stroke (RR 0.55, 0.33-0.92), and coronary revascularization (RR 0.73, 0.60-0.90) compared with NPC1L1 inhibitor, and it provided a larger reduction in the risk of MACE (RR 0.79, 0.69-0.91) compared to PCSK9 inhibitor. However, colchicine was associated with increased risk of non-cardiovascular death compared with NPC1L1 inhibitor (RR 1.48, 1.04-2.10) and PCSK9 inhibitor (RR 1.57, 1.08-2.27). Although no regimen prolonged survival, colchicine had worse performance on non-cardiovascular death and all-cause mortality. CONCLUSIONS: In patients with ASCVD receiving statin, colchicine seems to be more effective than intensive LDL-C-lowering therapy with PCSK9 inhibitor or NPC1L1 inhibitor for cardiovascular prevention. However, using colchicine as an alternative to intensive LDL-C-lowering therapy may need to be weighed against the cardiovascular benefits and the potential harms of higher non-cardiovascular death. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023441385.
目的：已证明在他汀类药物基础上加用强化降低低密度脂蛋白胆固醇（LDL-C）药物或秋水仙碱，可为动脉粥样硬化性心血管疾病（ASCVD）患者带来额外的心血管益处。我们旨在比较这些补充药物在接受他汀类药物治疗的ASCVD患者中的疗效和安全性。 方法：我们对随机对照试验进行了系统评价和频率学派网状荟萃分析。主要疗效终点是主要不良心血管事件（MACE），次要疗效终点分别是心肌梗死、中风、冠状动脉血运重建、心血管死亡和全因死亡率。安全性终点是治疗中断和非心血管死亡。我们获得了疗效结局和安全性终点的估计值，并将这些估计值表示为具有95%置信区间的风险比（RR）。我们用P值对所有药物的比较疗效和安全性进行排名。 结果：共纳入17项试验，总计85823名参与者，其中接受秋水仙碱治疗的有5926名参与者，通过前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂、尼曼-匹克C1样1蛋白（NPC1L1）抑制剂或ATP柠檬酸裂解酶（ACL）抑制剂进行强化LDL-C降低治疗的有37854名参与者，单独接受他汀类药物治疗的有42043名参与者。与NPC1L1抑制剂相比，秋水仙碱与MACE风险（RR 0.72，0.69 - 0.91）、中风风险（RR 0.55，0.33 - 0.92）和冠状动脉血运重建风险（RR 0.73，0.60 - 0.90）的更大降低相关，与PCSK9抑制剂相比，它使MACE风险降低幅度更大（RR 0.79，0.69 - 0.91）。然而，与NPC1L1抑制剂（RR 1.48，1.04 - 2.10）和PCSK9抑制剂（RR 1.57，1.08 - 2.27）相比，秋水仙碱与非心血管死亡风险增加相关。尽管没有一种治疗方案能延长生存期，但秋水仙碱在非心血管死亡和全因死亡率方面表现较差。 结论：在接受他汀类药物治疗的ASCVD患者中，秋水仙碱在心血管预防方面似乎比使用PCSK9抑制剂或NPC1L1抑制剂进行强化LDL-C降低治疗更有效。然而，将秋水仙碱用作强化LDL-C降低治疗的替代方案可能需要权衡心血管益处和非心血管死亡风险增加的潜在危害。 试验注册：PROSPERO标识符：CRD42023441385。
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