Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study.
BACKGROUND
Contrast media cause oxidative stress, which has been suggested as one possible mechanism responsible for contrast-induced nephropathy. Statins appear to have pleiotropic effects, including antioxidant properties. We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography.


METHODS
We conducted a prospective, randomized, double-blind, placebo-controlled, 2-center trial, involving 247 consecutive patients with chronic renal insufficiency (calculated creatinine clearance < or = 60 mL/min and/or serum creatinine > or = 1.1 mg/dL) undergoing coronary angiography. Patients were randomized to simvastatin (n = 124; 160 mg total, 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure) or placebo (n = 123). All patients received pre - and postprocedure hydration. The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients.


RESULTS
There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography, the primary study end point (0.002 +/- 0.164 vs 0.017 +/- 0.230 mg/mL respectively, P = .559). The incidence of contrast-induced nephropathy, a secondary end point defined as increase of either > or = 25% or > or = 0.5 mg/dL in serum creatinine, was 2.5% in simvastatin-treated patients (3/118) and 3.4% in placebo-treated patients (4/118), a nonsignificant difference (P = 1.00). There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes.


CONCLUSIONS
Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography.
Jo
Sang-Ho
SH
Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine/Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea.
Koo
Bon-Kwon
BK
Park
Jin-Shik
JS
Kang
Hyun-Jae
HJ
Cho
Young-Seok
YS
Kim
Yong-Jin
YJ
Youn
Tae-Jin
TJ
Chung
Woo-Young
WY
Chae
In-Ho
IH
Choi
Dong-Ju
DJ
Sohn
Dae-Won
DW
Oh
Byung-Hee
BH
Park
Young-Bae
YB
Choi
Yun-Shik
YS
Kim
Hyo-Soo
HS
D000284:Administration, Oral; D000368:Aged; D003287:Contrast Media / Q000009:adverse effects*; D017023:Coronary Angiography / Q000009:adverse effects*; D003327:Coronary Disease / Q000150:complications / Q000000981:diagnostic imaging*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D015994:Incidence; D007723:Korea / Q000453:epidemiology; D008297:Male; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000139:chemically induced / Q000150:complications* / Q000453:epidemiology / Q000517:prevention & control*; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014283:Triiodobenzoic Acids / Q000009:adverse effects
D003287:Contrast Media; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014283:Triiodobenzoic Acids; D019821:Simvastatin; C044834:iodixanol