University of Colorado-Anschutz Medical Campus, Aurora.
Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Clin Infect Dis. 2017 Nov 29;65(12):2042-2049. doi: 10.1093/cid/cix645.
Although statins, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are generally well tolerated, the impact of these therapies individually or in combination on the change in neurocognitive function in persons with human immunodeficiency virus infection is unknown.
The study included participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort participants not receiving a statin or ACEI/ARB within 30 days of first neurologic assessment (baseline), with assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit symbol test [DST]) from ≥2 measurements. Marginal structural models estimated the causal effect of statin or ACEI/ARB initiation on neurocognitive function; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter.
Of 3949 eligible participants, 16% started therapy with a statin, 11% with an ACEI/ARB, and 5% with both. Statin therapy had no significant effect on the composite NPZ-3 (primary outcome), Trailmaking B test, or DST. A small, nonsignificant positive effect on the Trailmaking A test was seen during year 1 (estimate, 0.088; 95% confidence interval, -.010 to .187; P = .08) and a small but significant negative effect (-0.033; -.058 to -.009; P = .007) in each subsequent year. ACEI/ARB therapy had a significant negative effect on the DST (-0.117; 95% confidence interval, -.217 to .016; P = .02) during year 1 but minimal effect in subsequent years or on other neurocognitive domains.
In summary, although modest declines in neurocognitive performance were seen in single domains with statin or ACEI/ARB therapy, we did not find consistent evidence that statins or ACEI/ARB have an effect on global neurocognitive function. Future studies should focus on long-term neurocognitive effects.
尽管他汀类药物、血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体阻滞剂(ARB)通常具有良好的耐受性,但这些治疗方法单独或联合使用对人类免疫缺陷病毒感染患者神经认知功能变化的影响尚不清楚。
该研究纳入了 AIDS 临床试验组纵向关联随机试验队列中的参与者,这些参与者在首次神经评估(基线)的 30 天内没有接受他汀类药物或 ACEI/ARB 治疗,且至少有 2 次 NPZ-3(Trailmaking A 和 B 测试以及数字符号测试 [DST] 的平均值 Z 分数)评估结果。边缘结构模型估计了他汀类药物或 ACEI/ARB 起始治疗对神经认知功能的因果影响;治疗的最初一年采用固定斜率,此后采用第二固定斜率。
在 3949 名符合条件的参与者中,16%开始接受他汀类药物治疗,11%开始接受 ACEI/ARB 治疗,5%同时接受两种治疗。他汀类药物治疗对 NPZ-3 综合评分(主要结局)、Trailmaking B 测试或 DST 均无显著影响。在第一年观察到对 Trailmaking A 测试有小但无统计学意义的正向影响(估计值,0.088;95%置信区间,-.010 至.187;P =.08),随后每年的影响均较小但有统计学意义(-.033;-.058 至 -.009;P =.007)。ACEI/ARB 治疗在第一年对 DST 有显著的负向影响(-0.117;95%置信区间,-.217 至.016;P =.02),但在随后的几年或其他神经认知领域的影响较小。
总之,尽管他汀类药物或 ACEI/ARB 治疗在单一领域会导致神经认知表现略有下降,但我们并未发现一致的证据表明他汀类药物或 ACEI/ARB 对整体神经认知功能有影响。未来的研究应关注长期的神经认知影响。