Elsevier

American Heart Journal

Volume 155, Issue 3, March 2008, Pages 499.e1-499.e8
American Heart Journal

Clinical Investigation
Coronary Artery Disease
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

https://doi.org/10.1016/j.ahj.2007.11.042Get rights and content

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 ≤60 mL/min and/or serum creatinine ≥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 ≥25% 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.

Section snippets

Study population

The PROMISS trial was conducted in 2 national hospitals in Korea: Seoul National University Hospital, Seoul, Korea, and Seoul National University Bundang Hospital, Gyeonggi-do, Korea. A total of 3080 patients referred for coronary catheterization and/or coronary intervention were screened for eligibility from February 2005 through January 2006. Patients aged ≥19 years with creatinine clearance (CrCl) rates ≤60 mL/min (calculated using the Cockcroft-Gault formula)18 or baseline serum creatinine

Patient population and baseline characteristics

Between February 2005 and January 2006, a total of 3080 consecutive patients were screened. Among them, 490 patients with a basal CrCl ≤60 mL/min and/or a SCr ≥1.1 mg/dL were considered eligible for participation. Eight patients declined participation, 2 were excluded because of chronic dialysis, and 233 were excluded because they were on statin medication. Thus, 247 patients were randomized, 124 to receive simvastatin and 123 to receive placebo, and included in the intention-to-treat analyses (

Contrast-induced nephropathy prevention by antioxidants

Oxidative stress is considered an important mechanism in the development of CIN, based on evidence indicating a role for reactive oxygen species in contrast-mediated renal injury.6, 7 The antioxidant NAC has been investigated extensively as an agent for CIN prevention. Representative findings have demonstrated an increased benefit of NAC added to prophylactic hydration alone7 and, more recently, greater efficacy with increased NAC dosing (1200 vs 600 mg, twice daily),21 consistent with the

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    Clinical Trial Registration: www.ClinicalTrials.gov; Identifier: NCT00259441.

    This study was supported by a grant from the Innovative Research Institute for Cell Therapy, Department of Internal Medicine, Seoul National University/Cardiovascular Center, (A062260) and the Clinical Research Center for Ischemic Heart Disease, Seoul, Republic of Korea, (0412-CR02-0704-0001) sponsored by the Ministry of Health & Welfare, Republic of Korea.

    d

    The affiliation of the author has changed from Seoul National University Hospital to Hallym University Sacred Heart Hospital since this work was completed.

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