Solomon Scott D, Rice Madeline M, A Jablonski Kathleen, Jose Powell, Domanski Michael, Sabatine Marc, Gersh Bernard J, Rouleau Jean, Pfeffer Marc A, Braunwald Eugene
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115, USA.
Circulation. 2006 Jul 4;114(1):26-31. doi: 10.1161/CIRCULATIONAHA.105.592733. Epub 2006 Jun 26.
Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.
We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).
Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.
肾功能减退的患者发生不良心血管事件的风险增加。在心肌梗死后的情况下，血管紧张素转换酶（ACE）抑制剂已被证明在肾功能受损的患者中与肾功能正常的患者一样有效。
我们在参加ACE抑制剂预防事件试验（PEACE）的稳定冠状动脉疾病且收缩功能正常的患者中，评估了肾功能与结局之间的关系、ACE抑制对此关系的影响，以及肾功能是否会改变ACE抑制的有效性。患者（n = 8290）被随机分配接受群多普利（目标剂量，4 mg/d）或安慰剂。随机分组前，8280例患者有临床肌酐测量值。采用4变量肾病饮食改良公式计算估计肾小球滤过率（eGFR）。肾功能与结局相关，并通过正式的交互作用模型评估ACE抑制剂治疗的影响。PEACE研究中的平均eGFR为77.6±19.4，1355例（16.3%）患者肾功能减退（eGFR<60 mg·mL⁻¹·1.73 m⁻²）。我们观察到eGFR与治疗组在心血管和全因死亡率方面存在显著交互作用（P = 0.02）。群多普利与肾功能减退患者的总死亡率降低相关（校正HR，0.73；95%CI，0.54至1.00），但与肾功能正常患者的总死亡率降低无关（校正HR，0.94；95%CI，0.78至1.13）。
虽然群多普利在平均eGFR相对较高的整个PEACE队列中未改善生存率，但群多普利降低了eGFR降低患者的死亡率。这些数据表明，肾功能减退可能确定了最有可能从ACE抑制剂治疗中获得心血管保护益处的患者亚组。
