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CAR--CKD associated with higher risk for all major CV events after MI; captopril appears to reduce CV events regardless of baseline kidney function

Sunday, January 02 2005 | Comments

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What's This? Chronic kidney disease (CKD) appears to be associated with a heightened risk for all major cardiovascular (CV) events after myocardial infarction (MI), especially among patients with an estimated glomerular filtration rate (eGFR) of <45 mL min-1 1.73m-2, according to a new study. Data also revealed that randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function. The study included 2,183 subjects enrolled in the Survival And Ventricular Enlargement (SAVE) trial. All participants had left ventricular ejection fraction <=40%, serum creatinine <2.5 mg/dL, and had recently experienced MI; 719 patients had CKD. Subjects were randomized to either captopril or placebo between 3 to 16 days post-MI. Investigators used the 4-variable Modification of Diet in Renal Disease method to calculate eGFR. Reduced eGFR was analyzed based on 4 ranges: >= 75 (referent), 60 to 74, 45 to 59, and <45 mL min-1 1.73m-2. The mean baseline eGFR in study subjects was 70.0 mL min-1 1.73m-2. Data showed that even mild reductions in eGFR were associated with a higher risk of all CV events. Compared with the referent range, the multivariable adjusted risk ratios for total mortality associated with reduced eGFR were 1.11 (0.86 to 1.42) for eGFR from 60 to 74 mL min-1 1.73m-2; 1.24 (0.96 to 1.60) for eGFR 45 to 59 mL min-1 1.73m-2; and 1.81 (1.32 to 2.48) for eGFR <45 mL min-1 1.73m-2 (P=.001 for trend). Similar results were seen for CV mortality (P=.001), recurrent MI (P=.017), and a combined CV mortality and morbidity outcome (P=.002). Lower eGFR was also associated with a nonsignificant trend (P=.07) toward a greater risk of developing heart failure. Data showed the use of captopril in subjects with CKD had a slightly higher relative risk reduction compared to subjects without CKD using captopril (31% vs 20%) although the interaction between captopril and CKD was not statistically significant (P=.29). However, because of the higher event rate in subjects with CKD, the absolute benefit of captopril was greater in those subjects. Per 100 subjects with CKD, captopril prevented 12.4 CV events compared with 5.5 CV events in those without CKD. "An eGFR of approximately 60 mL min-1 1.73m-2 may be considered as a threshold value below which the relative risk of CV events increases more rapidly and in a nonlinear fashion," the study authors said. "Absent major contraindications (eg, refractory hyperkalemia), these data suggest that ACE inhibitors should be routinely administered to patients with CKD after MI." (Tokmakova MP, et al. Circulation 2004;110:3667-73.)

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