High Dose Atorvastatin May Prevent Contrast-Induced Kidney Injury in Elective PCI

Pre-treatment with high-dose atorvastatin may prevent contrast-media induced acute kidney injury (AKI) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI), according to results from a subanalysis of the NAPLES II trial. However, the study, published online November 12, 2012, ahead of print in Circulation, found that the advantage of adding the statin to standard preventive therapy was effective only in low-to-medium risk patients.

In the main NAPLES (Novel Approaches for Preventing or Limiting Events) II trial, researchers randomized 668 statin-naïve patients from 2 Italian centers who were scheduled for elective PCI to atorvastatin (n = 338; 80 mg given within 24 hours pre-procedure) or no atorvastatin (n = 330). Patients receiving atorvastatin had a lower incidence of periprocedural MI and lower cardiac troponin I levels. The results were presented in March 2009 at the American College of Cardiology annual meeting.

For the subanalysis, Carlo Briguori, MD, PhD, of Clinica Mediterranea (Naples, Italy), and colleagues looked at the effect of atorvastatin in the 410 patients in NAPLES II who had CKD.

Atorvastatin Advantage

Contrast-induced AKI, defined as an increase of more than 10% in serum cystatin C concentration within 24 hours after contrast media exposure (the primary endpoint), occurred in fewer patients treated with atorvastatin compared with controls. In addition, serum creatinine levels increased more in the control group than in the statin group (table 1).

Table 1. Primary and Secondary Endpoints

 
The finding of less contrast-induced AKI was consistent in both diabetic and nondiabetic patients as well as in those with moderate CKD (eGFR 31-60 ml/min/1.73 m²). However, no advantage for atorvastatin was evident in patients with severe CKD (eGFR ≤ 30).

At 1-year follow up, the rate of major adverse events was 9% (death in 7%, chronic dialysis in 2%). These events occurred more often in patients with contrast-induced AKI vs. those without the condition (20% vs. 7.8%; P = 0.013).

A separate group of 20 patients with CKD who were not part of the original NAPLES II trial was assessed to determine the effect of atorvastatin loading dose on renal function in the absence of contrast media exposure, using serum creatinine and cystatin C. These markers were measured simultaneously before and 24 h and 48 h after atorvastatin administration. Overall, there was no significant change in either marker.

The researchers also evaluated the effects of atorvastatin pretreatment on survival signals mediated by 2 signal transduction pathways and found that atorvastatin increased and almost completely restored the survival signal in kidney cells.

“The present study shows the additive protective effect of atorvastatin over the combined administration of sodium bicarbonate solution and [N-acetylcysteine]: this supports the hypothesis that the combination of different antioxidant compounds seems to be more effective than a single agent in preventing [contrast-induced] AKI,” the study authors write. However, they add that several issues “need to be addressed before reaching the strong conclusion that NAC should be abandoned.” These include baseline CKD severity, consistency of hydration protocol, and impact of contrast-media selection.

All patients with CKD received N-acetylcysteine and hydration with sodium bicarbonate solution. The contrast agent used in all patients was iodixanol.

Significance Unclear

In a telephone interview with TCTMD, Hitinder S. Gurm, MD, of the University of Michigan Medical Center (Ann Arbor, MI), said while the study is interesting and well done, it does not make a strong case for the use of high-dose statins to prevent AKI.

“I don’t think this study is robust enough that we should change practice,” he said. Despite the many other benefits of statins, he added, “I don’t think we should start loading patients up with statins for the sole purpose of reducing contrast-induced kidney injury.”

Dr. Gurm said the finding that patients with less severe kidney disease benefited the most from statin treatment is an “interesting paradox” because it suggests that those most vulnerable and in need of protection from the statin were not helped by the drug. He pointed out that 2 previous studies—using atorvastatin and simvastatin, respectively—did not find an advantage for statin preloading in reducing kidney injury, so more research is needed to clarify any potential for benefit.

“The challenge with contrast induced nephropathy in general is that most studies that are published are small, and what we need is 1 or 2 large multicenter studies to arrive at a clear answer as to whether [statins] are or are not an effective therapy,” Dr. Gurm said.

 

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Source:
Quintavalle C, Fiore D, De Micco F, et al. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. Circulation. 2012;Epub ahead of print.

 

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