Lancet Diabetes Endocrinol. 2016 Oct;4(10):829-39. doi: 10.1016/S2213-8587(16)30156-5. Epub 2016 Jul 29.
Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain.
We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol.
Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR.
Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits.
UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.
他汀类药物治疗对预防轻度至中度慢性肾脏病患者的冠心病和中风是有效的，但在疾病更严重的患者中，特别是在接受透析的患者中，其效果尚不确定。
我们对来自 28 项试验的 183419 名参与者的个体参与者数据进行了荟萃分析，研究了基于他汀类药物的治疗对主要血管事件（主要冠状动脉事件[非致命性心肌梗死或冠状动脉死亡]、中风或冠状动脉血运重建）和特定原因死亡率的影响。参与者根据基线时估计肾小球滤过率（eGFR）分为不同类别。使用 LDL 胆固醇每降低 1mmol/L 的率比（RR）来估计治疗效果。
总体而言，基于他汀类药物的治疗使首次主要血管事件的风险降低了 21%（RR0·79，95%CI0·77-0·81；p<0·0001），每降低 1mmol/L LDL 胆固醇。随着 eGFR 的下降，观察到对主要血管事件的相对影响较小（趋势 p=0·008；eGFR≥60mL/min/1·73m(2)时 RR0·78，99%CI0·75-0·82；eGFR45 至<60mL/min/1·73m(2)时 RR0·76，0·70-0·81；eGFR30 至<45mL/min/1·73m(2)时 RR0·85，0·75-0·96；eGFR<30mL/min/1·73m(2)且未接受透析时 RR0·85，0·71-1·02；接受透析的患者 RR0·94，0·79-1·11）。主要冠状动脉事件（趋势 p=0·01）和血管死亡率（趋势 p=0·03）也存在类似的按基线肾功能分层的趋势，但冠状动脉血运重建没有显著趋势（p=0·90）。无论 eGFR 如何，使用基于他汀类药物的治疗降低 LDL 胆固醇对非血管死亡率均无影响。
即使考虑到更严重的慢性肾脏病患者实现的 LDL 胆固醇降低幅度较小，以及透析试验之间结局定义的差异，基于他汀类药物的治疗观察到的主要血管事件的相对降低随着 eGFR 的下降而减小，接受透析的患者几乎没有获益的证据。在慢性肾脏病患者中，应选择基于他汀类药物的治疗方案，以最大限度地降低 LDL 胆固醇的绝对降幅，从而获得最大的治疗益处。
英国医学研究理事会、英国心脏基金会、英国癌症研究中心、欧洲共同体生物医学计划、澳大利亚国家卫生和医学研究理事会、澳大利亚国家心脏基金会。
