Chronic kidney disease, cardiovascular risk, and response to angiotensin-converting enzyme inhibition after myocardial infarction: the Survival And Ventricular Enlargement (SAVE) study.
BACKGROUND
Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease (CKD) have an increased risk of death after myocardial infarction (MI) that is not fully explained by associated comorbidities. Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized.


RESULTS
We calculated the estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days after MI) with left ventricular ejection fraction < or =40% and serum creatinine <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR. Subjects with reduced eGFR were older and had more extensive comorbidities. The multivariable adjusted risk ratio for total mortality associated with reduced eGFR from 60 to 74, 45 to 59, and <45 mL x min(-1) x 1.73 m(-2) (compared with eGFR > or =75 mL x min(-1) x 1.73 m(-2)) was 1.11 (0.86 to 1.42), 1.24 (0.96 to 1.60) and 1.81 (1.32 to 2.48), respectively (P for trend =0.001). Similar adjusted trends were present for CV mortality (P=0.001), recurrent MI (P=0.017), and the combined CV mortality and morbidity outcome (P=0.002). The absolute benefit of captopril tended to be greater in subjects with CKD: 12.4 versus 5.5 CV events prevented per 100 subjects with (n=719) and without (n=1464) CKD, respectively.


CONCLUSIONS
CKD was associated with a heightened risk for all major CV events after MI, particularly among subjects with an estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2). Randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function.
Tokmakova
Mariya P
MP
Department of Cardiology, St. George Hospital, Medical University Plovdiv, Plovdiv, Bulgaria.
Skali
Hicham
H
Kenchaiah
Satish
S
Braunwald
Eugene
E
Rouleau
Jean L
JL
Packer
Milton
M
Chertow
Glenn M
GM
Moyé
Lemuel A
LA
Pfeffer
Marc A
MA
Solomon
Scott D
SD
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012306:Risk
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril