Efficacy and Safety of Very Low Achieved LDL Cholesterol in Patients With Previous Ischemic Stroke.

The benefits of achieving very low levels of low-density lipoprotein cholesterol (LDL-C) in such patients is unclear.

在这些患者中达到非常低的低密度脂蛋白胆固醇（LDL-C）水平的益处尚不明确。

Methods

We analyzed patients with previous ischemic stroke enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), a randomized placebo-controlledtrial studying evolocumab in patients with stable atherosclerotic cardiovascular disease (median follow-up, 2.2 years), and through the open-label extension (FOURIER-OLE) period (additional median follow-up, 5 years), to examine the relationship between achieved LDL-C and the long-term incidenceof the primary end point (cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization) and stroke-related end points.

我们分析了在FOURIER（进一步的心血管结果研究，使用PCSK9抑制剂针对高风险患者）中登记的既往有缺血性中风病史的患者，这是一项随机安慰剂对照试验，研究了在稳定动脉粥样硬化心血管疾病患者中使用evolocumab的效果（中位随访期为2.2年），并通过开放标签扩展（FOURIER-OLE）期间（额外的中位随访期为5年），以检查达到的LDL-C水平与主要终点（心血管死亡、心肌梗死、中风或因不稳定型心绞痛住院或冠状动脉血运重建）和中风相关终点的长期发生率之间的关系。

Results

The analysis included 5291 patients with previous ischemic stroke (>4 weeks).

分析包括了5291名既往有缺血性中风病史的患者（>4周）。

Of these, 666 (12.6%), 1410 (26.6%), 586 (11.1%), 508 (9.6%), and 2121 (40.1%) patients achieved LDL-C values of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively.

在这些患者中，分别有666名（12.6%）、1410名（26.6%）、586名（11.1%）、508名（9.6%）和2121名（40.1%）达到了LDL-C值<20、20至<40、40至<55、55至<70和≥70 mg/dL。

The incidenceof the primary end point, all stroke, and ischemic stroke each decreased in a monotonic fashion with lower achieved LDL-C levels on a continuous scale (Ptrend<0.001, 0.002, and 0.002, respectively).

主要终点事件的发生率、所有中风和缺血性中风的发生率均随着实现的LDL-C水平的降低而单调下降（Ptrend分别为<0.001、0.002和0.002）。

Compared with patients with LDL-C ≥70 mg/dL, those who achieved levels <40 mg/dL had incidencerate ratios of 0.69 (95% CI, 0.57-0.84), 0.73 (95% CI, 0.53-0.99), and 0.75 (95% CI, 0.54-1.05) for the outcomes of the primary end point, all stroke, and ischemic stroke, respectively.

与 LDL-C ≥70 mg/dL 的患者相比，LDL-C <40 mg/dL 的患者在主要终点事件、所有中风和缺血性中风的发生率比分别为 0.69 (95% CI, 0.57-0.84)、0.73 (95% CI, 0.53-0.99) 和 0.75 (95% CI, 0.54-1.05)。

Hemorrhagic strokes were infrequent and unrelated to achieved LDL-C (Ptrend=0.85).

出血性中风发生率较低，且与达到的 LDL-C 水平无关 (Ptrend=0.85)。

Conclusions

In patients with previous ischemic stroke, it appeared that the lower the LDL-C, down to levels <40 mg/dL, the lower the risk of major adverse cardiovascular events, including recurrent stroke, without a clear increase in risk of hemorrhagic stroke.

在有先前缺血性中风病史的患者中，似乎低密度脂蛋白胆固醇（LDL-C）水平越低，降至40 mg/dL以下，主要不良心血管事件的风险就越低，包括复发性中风，而并没有出现明显的出血性中风风险增加。

These findings support the concept that more intensive LDL-C lowering in patients with previous ischemic stroke may be warranted.

这些发现支持这样一个概念：对于有先前缺血性中风病史的患者，可能有必要进行更积极的低密度脂蛋白胆固醇（LDL-C）降低治疗。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01764633/NCT01764633.

网址: https://www.clinicaltrials.gov; 唯一标识符: NCT01764633/NCT01764633.