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.

Author(s): Jo SH, Koo BK, Park JS, Kang HJ, Cho YS, Kim YJ, Youn TJ, Chung WY, Chae IH, Choi DJ, Sohn DW, Oh BH, Park YB, Choi YS, Kim HS

Affiliation(s): Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine/Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea.

Publication date & source: 2008-03, Am Heart J., 155(3):499.e1-8. Epub 2008 Jan 30.

Publication type: Comparative Study; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.