Department of Internal Medicine, Division of Cardiology, University of Michigan Health System, Ann Arbor, MI, USA.
Am Heart J. 2010 Oct;160(4):701-14. doi: 10.1016/j.ahj.2010.06.029.
Carotid intima-media thickness (CIMT) is increasingly being used as a surrogate end point in randomized control trials (RCTs) of novel cardiovascular therapies. However, it remains unclear whether changes in CIMT that result from these therapies correlate with nonfatal myocardial infarction (MI).
We performed a literature search of RCTs from 1990-2009 that used CIMT. Eligible RCTs (1) included quantitative and sequential assessments in CIMT at least 1 year apart and (2) reported nonfatal MI. Across RCTs, random-effects metaregression was employed to correlate differences in mean change in CIMT between treatment and control groups over time with the log odds ratios of developing nonfatal MI during follow-up.
Overall, we identified 28 RCTs with 15,598 patients. Differences in mean change in CIMT over time between treatment and control groups correlated with developing nonfatal MI during follow-up: for each 0.01 mm per year smaller rate of change in CIMT, the odds ratio for MI was 0.82 (95% CI, 0.69 to 0.96; P = .018). Results were similar in subgroups of RCTs with >1 year follow-up (P = .018) and those with at least 50 subjects in the treatment group (P = .019). However, there was no significant relationship between mean change in CIMT and nonfatal MI in RCTs evaluating statin therapy or those with high CIMTs at baseline (P > .20 in both instances).
Less progression in CIMT over time is associated with a lower likelihood of nonfatal MI in selected RCTs; however, these findings were inconsistent at times, suggesting caution in using CIMT as a surrogate end point.
颈总动脉内膜中层厚度（CIMT）越来越多地被用作新型心血管治疗药物的随机对照试验（RCT）的替代终点。然而，这些疗法导致的 CIMT 变化是否与非致命性心肌梗死（MI）相关仍不清楚。
我们对 1990 年至 2009 年期间使用 CIMT 的 RCT 进行了文献检索。合格的 RCT 包括：（1）至少相隔 1 年进行的 CIMT 的定量和连续评估；（2）报告非致命性 MI。在整个 RCT 中，我们采用随机效应荟萃回归，将治疗组和对照组之间 CIMT 平均变化差异与随访期间非致命性 MI 发生率的对数优势比相关联。
总共，我们确定了 28 项 RCT，涉及 15598 名患者。治疗组和对照组之间 CIMT 随时间的平均变化差异与随访期间非致命性 MI 的发生相关：CIMT 每年变化率每减少 0.01 毫米，MI 的比值比为 0.82（95%CI，0.69 至 0.96；P =.018）。在随访时间超过 1 年的 RCT 亚组（P =.018）和治疗组至少有 50 名患者的 RCT 亚组（P =.019）中，结果相似。然而，在评估他汀类药物治疗的 RCT 或基线 CIMT 较高的 RCT 中，CIMT 的平均变化与非致命性 MI 之间没有显著关系（在两种情况下，P >.20）。
随着时间的推移，CIMT 的进展较慢与选定的 RCT 中非致命性 MI 的可能性降低相关；然而，这些发现有时不一致，表明在使用 CIMT 作为替代终点时应谨慎。
