Tonelli Marcello, Collins Dorothea, Robins Sander, Bloomfield Hanna, Curhan Gary C
Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Kidney Int. 2004 Sep;66(3):1123-30. doi: 10.1111/j.1523-1755.2004.00862.x.
Although cardiovascular disease and low high-density lipoprotein (HDL) cholesterol are common in people with renal insufficiency, data addressing the cardiovascular benefits of fibric acid derivatives in this population are sparse. We conducted a post hoc subgroup analysis of a randomized double-blind, placebo-controlled trial to determine whether gemfibrozil is effective and safe for secondary prevention of cardiovascular events in individuals with chronic renal insufficiency (CRI).
Using an analysis plan that was developed a priori, we analyzed data from the Veterans' Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) study; a randomized trial of gemfibrozil versus placebo in 2531 men with established coronary disease, an HDL cholesterol level of 40 mg/dL (1.0 mmol/L) or less, and a low-density lipoprotein (LDL) cholesterol level of 140 mg/dL (3.6 mmol/L) or less. Of these, 1046 men had CRI as defined by creatinine clearance </=75 mL/min using the Cockcroft-Gault equation, 99.8% of whom had either mild or moderate renal impairment (creatinine clearance 60-75 or 30-59.9 mL/min, respectively).
The incidence of the primary outcome (coronary death or nonfatal myocardial infarction) was lower in participants with CRI who received gemfibrozil compared to placebo [hazard ratio (HR) 0.73; 95% CI 0.56-0.96, P= 0.02). The cumulative incidence of the primary end point was reduced from 24.3% to 18.2%. In subjects with CRI, gemfibrozil also significantly reduced the risk of the combined outcome of coronary death, nonfatal myocardial infarction, or stroke (HR 0.74, 95% CI 0.58-0.95, P= 0.02), but not the need for coronary revascularization (HR 0.85, 95% CI 0.66-1.10, P= 0.21) or total mortality (HR 1.03, 95% CI 0.78-1.35, P= 0.85). The overall incidence of adverse effects was similar in individuals receiving gemfibrozil and placebo. However, the risk of sustained increases in serum creatinine was increased in gemfibrozil recipients compared with placebo (5.9 vs. 2.8%, P= 0.02).
Gemfibrozil appears effective for secondary prevention of cardiovascular events in individuals with mild to moderate chronic renal insufficiency and HDL cholesterol of 40 mg/dL or less. However, the benefit and safety of gemfibrozil in people with more severe impairment of kidney function requires further study.
尽管心血管疾病和低高密度脂蛋白（HDL）胆固醇在肾功能不全患者中很常见，但关于纤维酸衍生物对该人群心血管益处的数据却很少。我们对一项随机双盲、安慰剂对照试验进行了事后亚组分析，以确定吉非贝齐对慢性肾功能不全（CRI）患者心血管事件的二级预防是否有效和安全。
我们使用预先制定的分析方案，分析了退伍军人事务部高密度脂蛋白干预试验（VA-HIT）研究的数据；这是一项在2531名已确诊冠心病、HDL胆固醇水平为40mg/dL（1.0mmol/L）或更低、低密度脂蛋白（LDL）胆固醇水平为140mg/dL（3.6mmol/L）或更低的男性中进行的吉非贝齐与安慰剂对比的随机试验。其中，1046名男性根据Cockcroft-Gault方程肌酐清除率≤75mL/min被定义为患有CRI，其中99.8%患有轻度或中度肾功能损害（肌酐清除率分别为60 - 75或30 - 59.9mL/min）。
与接受安慰剂的CRI参与者相比，接受吉非贝齐的参与者主要结局（冠心病死亡或非致命性心肌梗死）的发生率更低[风险比（HR）0.73；95%置信区间0.56 - 0.96，P = 0.02]。主要终点的累积发生率从24.3%降至18.2%。在CRI患者中，吉非贝齐还显著降低了冠心病死亡、非致命性心肌梗死或中风联合结局的风险（HR 0.74，95%置信区间0.58 - 0.95，P = 0.02），但未降低冠状动脉血运重建的需求（HR 0.85，95%置信区间0.66 - 1.10，P = 0.21）或全因死亡率（HR 1.03，95%置信区间0.78 - 1.35，P = 0.85）。接受吉非贝齐和安慰剂的个体不良反应总体发生率相似。然而，与安慰剂相比，接受吉非贝齐者血清肌酐持续升高的风险增加（5.9%对2.8%，P = 0.02）。
吉非贝齐似乎对轻度至中度慢性肾功能不全且HDL胆固醇水平为40mg/dL或更低的个体心血管事件的二级预防有效。然而，吉非贝齐在肾功能损害更严重人群中的益处和安全性需要进一步研究。
