Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy.
Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy.
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DOI：
10.1161/circulationaha.118.034645
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发表时间：
2018-07-10
期刊：
影响因子：
37.8
通讯作者：
Ridker PM
中科院分区：
文献类型：
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作者：
Pradhan AD;Aday AW;Rose LM;Ridker PM
他汀类药物治疗和前蛋白转化酶枯草杆菌蛋白酶-kexin 9型（PCSK 9）抑制剂的组合显著降低低密度脂蛋白胆固醇（LDL-C），并降低心血管事件发生率。治疗中高敏C反应蛋白（hsCRP）是否仍是此类患者的一个重要临床问题尚不确定。我们评估了参与PCSK 9抑制和减少血管事件研究（SPIRE）-1和-2心血管结局试验的9，738例患者的残余炎症风险，这些患者接受他汀类药物治疗和bococizumab，根据治疗中hsCRP（hsCRPOT）和LDL-COT水平在药物开始后14周测量。主要终点为非致死性心肌梗死、非致死性卒中、因不稳定型心绞痛需要紧急血运重建而住院或心血管死亡。第14周时，他汀类药物治疗并额外接受bococizumab治疗的患者中LDL-C的平均百分比变化为− 60. 5%（95% CI − 61. 2至− 59. 8; p<0. 001;中位变化为− 65. 4%），而hsCRP为6. 6%（95% CI − 1. 0至14. 1; p= 0. 09;中位变化为0. 0%）。根据hsCRP <1、1-3和>3 mg/L的治疗水平，接受他汀类药物治疗和bococizumab治疗的患者未来心血管事件的发生率分别为1.96、2.50和3.59起事件/100人-年，对应于多变量校正的风险比分别为1.0、1.16和1.16（95% CI 0.81 - 1.66），1.62（95% CI 1.14 - 2.30）（p趋势=0.001），校正传统心血管风险因素和LDL-COT后。LDL-COT（<30、30-50、>50 mg/dL）的可比调整风险比分别为1.0、0.87和1.21（p趋势=0.16）。bococizumab的相对风险降低在hsCRPOT组之间相似（p-相互作用=0.87）。在稳定门诊人群中进行的Bococizumab SPIRE试验的事后分析中，在接受他汀类药物治疗和PCSK 9抑制治疗的患者中，残留炎症风险的证据持续存在。URL：https://clinicaltrials.gov唯一标识符：NCT 01975376、NCT 01975389
The combination of statin therapy and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain. We evaluated residual inflammatory risk among 9,738 patients participating in the Studies of PCSK9 Inhibition and the Reduction of Vascular Events (SPIRE)-1 and −2 cardiovascular outcomes trials who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRPOT) and LDL-COT measured 14 weeks after drug initiation. The primary endpoint was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death. At 14 weeks, the mean percent change in LDL-C among statin treated patients who additionally received bococizumab was −60.5% (95% CI −61.2 to −59.8; p<0.001; median change −65.4%) as compared to 6.6% (95% CI −1.0 to 14.1; p=0.09; median change 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to on treatment levels of hsCRP <1, 1-3, and >3 mg/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI 0.81 to 1.66), 1.62 (95% CI 1.14 to 2.30) (p-trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-COT. Comparable adjusted hazard ratios for LDL-COT (<30, 30-50, >50 mg/dL) were 1.0, 0.87, and 1.21, respectively (p-trend=0.16). Relative risk reductions with bococizumab were similar across hsCRPOT groups (p-interaction=0.87). In this post-hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and PCSK9 inhibition. URL: https://clinicaltrials.gov Unique Identifiers: NCT01975376, NCT01975389