The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid study found no evidence of a beneficial effect of statin-fibrate combined treatment, compared to statins alone, on cardiovascular outcomes and mortality in type 2 diabetes mellitus after 5 years of active treatment. However, a beneficial reduction in major CVD events was shown in a pre-specified sub-group of participants with dyslipidemia. The extended follow-up of this trial provides the opportunity to further investigate possible beneficial effects of fibrates in this group of patients. We aimed to evaluate possible “legacy effects” of fibrate add-on therapy on mortality and major cardiovascular outcomes in patients with dyslipidemia. The ACCORD-lipid study was a randomized controlled trial of 5518 participants assigned to receive simvastatin plus fenofibrate vs simvastatin plus placebo. After randomized treatment allocation had finished at the end of the trial, all surviving participants were invited to attend an extended follow-up study (ACCORDION) to continue prospective collection of clinical outcomes. We undertook a secondary analysis of trial and post-trial data in patients who had dyslipidemia. The primary outcome was all-cause and cardiovascular mortality, and secondary outcomes were nonfatal myocardial infarction, stroke, congestive heart failure and major coronary heart disease. We used an intention-to-treat approach to analysis to make comparisons between the original randomized treatment groups. 853 participants with dyslipidemia had survived at the end of the trial. Most participants continued to use statins, but few used fibrates in either group during the post-trial period. The incidence rates in the fenofibrate group were lower with respect to all-cause mortality, CVD mortality, nonfatal myocardial infarction, congestive heart failure and major coronary heart disease than those in the placebo group over a post-trial follow-up. Allocation to the combined fibrate-statin treatment arm during the trial period had a beneficial legacy effect on all-cause mortality (adjusted HR = 0.65, 95% CI 0.45–0.94; P = 0.02). Fibrate treatment during the initial trial period was associated with a legacy benefit of improved survival over a post-trial follow-up. These findings support re-evaluation of fibrates as an add-on strategy to statins in order to reduce cardiovascular risk in diabetic patients with dyslipidemia. Trial registration clinicaltrials.gov, Identifier: NCT00000620

中文翻译：

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贝特类附加疗法对合并血脂异常的糖尿病患者的遗留影响：ACCORDION 研究的二次分析。


控制糖尿病心血管风险行动 (ACCORD)-Lipid 研究发现，与单独使用他汀类药物相比，没有证据表明他汀类药物联合治疗对 2 型糖尿病患者经过 5 年积极治疗后的心血管结局和死亡率有有益影响。然而，在预先指定的血脂异常参与者亚组中，主要心血管事件的减少却显示出有益的效果。该试验的长期随访为进一步研究贝特类药物对这组患者可能产生的有益作用提供了机会。我们的目的是评估贝特类附加疗法对血脂异常患者的死亡率和主要心血管结局可能的“遗留影响”。 ACCORD-脂质研究是一项随机对照试验，共有 5518 名参与者被分配接受辛伐他汀加非诺贝特与辛伐他汀加安慰剂治疗。试验结束时随机治疗分配完成后，所有幸存参与者都被邀请参加一项扩展的随访研究 (ACCORDION)，以继续前瞻性收集临床结果。我们对血脂异常患者的试验和试验后数据进行了二次分析。主要结局是全因死亡率和心血管死亡率，次要结局是非致命性心肌梗死、中风、充血性心力衰竭和严重冠心病。我们使用意向治疗方法进行分析，以在原始随机治疗组之间进行比较。试验结束时，853 名患有血脂异常的参与者幸存。大多数参与者继续使用他汀类药物，但在试验后期间，两组中很少有人使用贝特类药物。 在试验后随访中，非诺贝特组的全因死亡率、心血管疾病死亡率、非致命性心肌梗塞、充血性心力衰竭和严重冠心病的发生率低于安慰剂组。试验期间分配至贝特-他汀联合治疗组对全因死亡率具有有益的遗留效应（调整后 HR = 0.65，95% CI 0.45–0.94；P = 0.02）。初始试验期间的贝特类治疗与试验后随访期间生存率改善的遗留效益相关。这些发现支持重新评估贝特类药物作为他汀类药物的附加策略，以降低血脂异常的糖尿病患者的心血管风险。试验注册临床试验。政府，标识符：NCT00000620