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

Am Heart J. 2008 Mar;155(3):499.e1-8. doi: 10.1016/j.ahj.2007.11.042. Epub 2008 Jan 30.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00259441.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Contrast Media / adverse effects*
  • Coronary Angiography / adverse effects*
  • Coronary Disease / complications
  • Coronary Disease / diagnostic imaging*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Incidence
  • Korea / epidemiology
  • Male
  • Prospective Studies
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / complications*
  • Renal Insufficiency / epidemiology
  • Renal Insufficiency / prevention & control*
  • Risk Factors
  • Simvastatin / administration & dosage*
  • Time Factors
  • Treatment Outcome
  • Triiodobenzoic Acids / adverse effects

Substances

  • Contrast Media
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Triiodobenzoic Acids
  • Simvastatin
  • iodixanol

Associated data

  • ClinicalTrials.gov/NCT00259441