Cardiology Division, Massachusetts General Hospital 55 Fruit St, GRB-800, Boston, MA 02114, USA.
J Clin Lipidol. 2011 Mar-Apr;5(2):97-104. doi: 10.1016/j.jacl.2011.01.006. Epub 2011 Feb 1.
Long-term follow-up of clinical trials with lipid-lowering medications has suggested a continuation of event reduction after study completion.
To evaluate the persistence of the benefit of lipid-lowering therapy in decreasing mortality after the end of clinical trials, when all patients were advised to take the same open-label lipid-lowering therapy.
Through searches of MEDLINE, the Cochrane Library, the Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov until June 2010 we identified randomized clinical trials of lipid-lowering agents with a second report describing results after the end of the trial.
Among the 459 trials reviewed, only 8 including 44,255 patients and 8144 deaths qualified for the meta-analysis. All-cause and cardiovascular mortality were lower in the active intervention group during the first phase (0.84, 95% confidence interval [CI] 0.76-0.93; P = .0006 and 0.72, 95% CI 0.63-0.82, P < .0001, respectively) when 71 ± 23% of the patients randomized to receive active therapy actually received it compared with 13 ± 5% of patients who received active therapy although they were randomized to placebo (P = .0001). The lower mortality among those initially randomized to active therapy persisted during the second phase (odds ratio 0.90, 95% CI 0.84-0.97, P = .0035, and 0.82 95% CI 0.73-0.93, P = .0014), when patients in both randomized groups received active therapy in the same proportions (5 ± 2% for both groups). Numerous sensitivity analyses support the conclusions of the paper.
The decrease in mortality with lipid-lowering therapy in clinical trials persists after discontinuation of randomized therapy when patients in the treatment and placebo groups receive active therapy.
降脂药物临床试验的长期随访表明，研究完成后仍能继续降低事件发生率。
评估降脂治疗在临床试验结束后继续降低死亡率的益处，此时所有患者均被建议使用相同的开放性降脂治疗。
通过对 MEDLINE、Cochrane 图书馆、中央对照试验注册处、Web of Science 和 ClinicalTrials.gov 的检索，截至 2010 年 6 月，我们共检索到 459 项降脂药物的随机临床试验，其中有 8 项研究在试验结束后进行了第二次报告，结果符合纳入标准。
在 459 项试验中，仅有 8 项（包括 44255 名患者和 8144 例死亡）符合荟萃分析的纳入标准。与安慰剂组相比，在随机接受活性治疗的患者中，活性干预组在第一阶段时全因死亡率和心血管死亡率更低[0.84，95%置信区间（CI）为 0.76-0.93；P =.0006 和 0.72，95%CI 为 0.63-0.82，P <.0001]，活性治疗组实际接受率为 71%±23%，而安慰剂组接受活性治疗的患者为 13%±5%，两组间差异有统计学意义（P =.0001）。在第二阶段，最初随机接受活性治疗的患者的死亡率仍较低[比值比（OR）0.90，95%CI 为 0.84-0.97，P =.0035 和 0.82，95%CI 为 0.73-0.93，P =.0014]，此时两组患者接受活性治疗的比例相同（两组均为 5%±2%）。大量敏感性分析支持本文的结论。
当治疗组和安慰剂组的患者均接受活性治疗时，临床试验中降脂治疗降低死亡率的效果在随机治疗停止后仍能持续。
