McCullough Peter A, Chinnaiyan Kavitha M
William Beaumont Hospital, Royal Oak, MI 48073, USA.
Arch Intern Med. 2009 Dec 14;169(22):2064-70. doi: 10.1001/archinternmed.2009.382.
Coronary artery calcification (CAC) measured by computed tomography is radiographic confirmation of atherosclerosis, predicts cardiovascular events, and has been evaluated as a surrogate measure in randomized trials.
We performed a literature search for prospective randomized trials in which CAC was measured at baseline and at 1 year or more of follow-up. We computed the weighted mean annualized rate of CAC progression for a variety of therapies tested in these trials.
Ten trials (n = 2612) met our criteria and were included. Electron-beam, double-helix, and multislice computed tomography were used in 6, 2, and 2 trials, respectively. Agatston (8 trials) and volumetric (2 trials) methods were used for CAC evaluation. In 5 trials in subjects with cardiovascular disease (CVD) (n = 2135; age, ~64 years; ~39% women; follow-up, ~26 months), therapies included statins (n = 1370), placebo (n = 564), and antihypertensives (n = 201). In 5 trials in subjects with chronic kidney disease (n = 477; age, ~55 years; ~34% women; follow-up, ~14 months), interventions included low-phosphorus diet (n = 29), sevelamer hydrochloride (n = 229), and calcium-based phosphate binders (n = 219). The mean (SD) weighted annualized CAC increase overall and in patients with CVD and chronic kidney disease was 17.2% (6.7%), 16.9% (5.2%), and 18.4 (11.1%), respectively (P < .001). The rate among those assigned blinded placebo was 14.6% (1.0%) (2 trials). There was no consistent or reproducible treatment effect of any therapy on this outcome measured at 1 year.
The 1-year change in CAC does not appear to be a suitable surrogate end point for treatment trials in patients with CVD or chronic kidney disease.
通过计算机断层扫描测量的冠状动脉钙化（CAC）是动脉粥样硬化的影像学确认指标，可预测心血管事件，并已在随机试验中作为替代指标进行评估。
我们对前瞻性随机试验进行了文献检索，这些试验在基线以及随访1年或更长时间时测量了CAC。我们计算了这些试验中测试的各种疗法的加权平均年化CAC进展率。
10项试验（n = 2612）符合我们的标准并被纳入。分别有6项、2项和2项试验使用了电子束计算机断层扫描、双螺旋计算机断层扫描和多层计算机断层扫描。分别有8项和2项试验使用阿加斯顿法和容积法评估CAC。在5项针对心血管疾病（CVD）患者的试验中（n = 2135；年龄约64岁；约39%为女性；随访约26个月），治疗方法包括他汀类药物（n = 1370）、安慰剂（n = 564）和抗高血压药物（n = 201）。在5项针对慢性肾病患者的试验中（n = 477；年龄约55岁；约34%为女性；随访约14个月），干预措施包括低磷饮食（n = 29）、盐酸司维拉姆（n = 229）和钙基磷酸盐结合剂（n = 219）。总体以及CVD和慢性肾病患者的平均（标准差）加权年化CAC增加分别为17.2%（6.7%）、16.9%（5.2%）和18.4%（11.1%）（P <.001）。分配到盲法安慰剂组的患者的进展率为14.6%（1.0%）（2项试验）。在1年时测量的该结果上，没有任何疗法具有一致或可重复的治疗效果。
对于CVD或慢性肾病患者的治疗试验，CAC的1年变化似乎不是一个合适的替代终点。
