Rosuvastatin Helps Stave Off Contrast Nephropathy in NSTE-ACS Patients

SAN FRANCISCO, CA—An early strategy of high-dose rosuvastatin exerts protective effects against contrast-induced nephropathy (CIN) and results in better short-term clinical outcomes in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) scheduled for intervention.

Anna Toso, MD, of Misericordia e Dolce Hospital (Prato, Italy), presented data from the PRATO-ACS trial in which 504 NSTE-ACS patients were randomly assigned to standard preventive therapy with (n = 271) or without rosuvastatin (n = 272; 40 mg on admission plus 20 mg daily until discharge). Patients were enrolled between July 2010 and August 2012, were statin naïve, and received iodixanol as the contrast agent prior to imaging.

Reduction in Nephropathy, Adverse Events

A total of 252 patients in each arm were included in the final analysis. At baseline, serum creatinine levels and creatinine clearance were similar between the rosuvastatin and control groups.

Development of CIN, defined as a rise in creatinine of at least 0.5 mg/dl or at least 25% from baseline within 72 hours—the primary endpoint— was significantly lower in patients randomized to rosuvastatin compared with controls (6.7% vs. 15.1%; P = 0.001). After adjustment for sex, age, diabetes and other confounders, statin treatment remained an independent predictor of reduced risk of CIN (OR 0.38; 95% CI 0.20-0.71). The number-needed-to-treat to prevent 1 case of CIN was 12.

Rosuvastatin showed comparable benefits when other definitions of kidney injury were used as well: creatinine increase of at least 0.3 mg/dl from baseline within 48 hours (OR 0.3; 95% CI 0.15-0.83) and within 72 hours (OR 0.36; 95% CI 0.17-0.77). The effect also was consistent across all pre-specified subgroups.

Furthermore, the rosuvastatin group had about half the 30-day cumulative occurrence of adverse events (persistent renal damage, dialysis, MI, stroke and death) compared with the control group (3.9% vs. 7.9%; P = 0.036). This was driven by a lower rate of persistent renal damage in the rosuvastatin-treated group (2% vs. 4.8%; P = 0.15), though the difference was not significant.

Statins for All?

“This study suggests that in NSTE-ACS patients scheduled for an early invasive strategy high-dose statins should be given on admission and in any case must precede the angiographic procedure in order to reduce renal complications after contrast medium administration,” Dr. Toso said.

It is hypothesized that the anti-lipidemic and pleiotropic properties of statins may exert a nephro-protective effect that results in improvement in endothelial function and reduction in oxidative stress. Current US and European guidelines recommend statins for all acute coronary syndrome patients, regardless of cholesterol levels, within 1 to 4 days after admission. But panel discussion centered on whether statins given before PCI to lower creatinine results in a reduction in ‘hard’ clinical events.

Panel member Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), commented that it is “difficult to show causality.” She added that it will be important to learn how to manage patients who are already on statins in terms of reloading. Dr. Toso said such patients are part of a parallel registry of PRATO-ACS.

Panel co-chair Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY) asked whether all PCI patients should be treated with a high statin loading dose.

Panel members said there is not enough evidence at this point to suggest such an approach for all patients but it should be used for those at high-risk of nephropathy. Another issue, they pointed out, is whether there is a class effect or if individual statins are more effective than others.

Study Details

All patients received standard preventive therapy (hydration plus N-acetylcystein). At discharge, patients in both groups received aspirin and clopidogrel. In addition, the rosuvastatin group continued to receive 20 mg per day (10 mg/day if creatinine clearance was less than 30 ml/min), while the control group received 40 mg per day of atorvastatin.

Note: Drs. Stone and Mehran are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:
Toso A. Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acute coronary syndrome. Presented at: American College of Cardiology Annual Scientific Session; March 9, 2013; San Francisco, CA.

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• Higher Statin Dose Lowers Contrast Nephropathy in ACS Patients