High-dose Statins Reduce CIN in ACS Patients Receiving PCI

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Pre-treatment with high-dose atorvastatin in statin-naïve patients prior to percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) reduces the risk of contrast induced nephropathy (CIN) by more than half compared with placebo, according to a randomized trial published online April 29, 2011, ahead of print in the American Journal of Cardiology.

For the ARMYDA-CIN (Atorvastatin for Reduction of MYocardial Damage during Angioplasty-Contrast-Induced Nephropathy) trial, researchers led by Germano Di Sciascio, MD, of the University of Rome (Rome, Italy), randomized 241 patients with NSTE ACS at 2 Italian institutions to pre-PCI high-dose atorvastatin (80 mg 12 hrs before intervention followed by 40 mg 3 hrs before) or placebo. All patients were given hydration with saline and no other renal-protective agents. While none of the patients received statins prior to the study, all patients received atorvastatin 40 mg/day after PCI regardless of initial randomization.

Patients receiving atorvastatin showed a relative reduction of 66% in the incidence of CIN, the primary endpoint (defined as a postintervention increase in serum creatinine [SCr] ≥ 0.5 mg/dL or > 25% from baseline), compared with placebo. Postprocedure SCr levels, peak C-reactive protein (CRP) levels, and length of hospital stay also were lower in the atorvastatin group, while creatinine clearance was increased (table 1).

Table 1. Postprocedural Outcomes 

The number of patients needed to treat with atorvastatin to prevent 1 case of CIN was 12. On multivariable analysis, atorvastatin pretreatment was independently associated with decreased risk of CIN (OR 0.34; 95% CI 0.12-0.97; P = 0.043). Age greater than 65 years and exceeding the maximum allowable contrast dose were independent predictors of increased risk.

Interestingly, peak CRP levels after intervention were higher in patients with CIN (22.4 ± 35.5 mg/L vs. 9.6 ± 13.0 mg/L; P = 0.006) regardless of treatment randomization, while in patients without CIN, atorvastatin resulted in a decrease in peak CRP levels (7.7 ± 9.2 mg/L vs. 11.7 ± 15.9 mg/L with placebo; P = 0.015).

Baseline and procedural characteristics were similar in the atorvastatin and placebo groups, with equivalent creatinine clearance and CRP levels, similar rates of diabetes and chronic renal failure, and equivalent mean procedural contrast volume.

“The randomized placebo-controlled ARMYDA-CIN trial demonstrates that short-term pretreatment with high-dose atorvastatin significantly decreases the occurrence of CIN in statin-naïve patients with ACS receiving early PCI,” the researchers conclude.

Inflammation Key Factor

Dr. Di Sciascio and colleagues add that there are multiple mechanisms by which atorvastatin may protect against renal dysfunction, but given the effects on CRP levels, “these findings confirm that inflammatory mechanisms may be involved in the pathogenesis of CIN and that renal protection by atorvastatin after PCI is probably due to their attenuation, although other pleiotropic effects may be responsible.”

Because ACS patients have “a high inflammatory status and ongoing endothelial dysfunction,” they note, such patients may derive the greatest benefit from statin pretreatment prior to angiography or PCI.

However, such a strategy will ultimately be judged on clinical outcomes. The researchers point out that in a previous study by the same group, CIN was associated with an absolute increase in cardiac events of 26% at 4 years. Therefore, an absolute decrease in CIN of 8%, as was observed in ARMYDA-CIN, would translate to 8 MACE events avoided for every 1,000 patients treated over 1 year.

Doubts Persist

But despite the positive results, outside experts contacted by TCTMD were more cautious in their assessments.

“The trial . . . is very small with only borderline significance (P = 0.046),” Richard J. Solomon, MD, of the University of Vermont (Burlington, VT), said in an e-mail communication. He also pointed to the lack of data on follow-up events, “which are of importance.”

Nevertheless, Dr. Solomon cited a soon-to-be published meta-analysis showing the preventive effect of statins on CIN. The study includes mainly low-risk patients, “similar to the patients in this trial,” Dr. Solomon said, adding that may be of little consequence to clinicians. “Cardiologists are less interested in low risk patients because the overall incidence of CIN is quite low (~2%).”

In a separate e-mail communication, Josef Veselka, MD, PhD, of Charles University Motol Medical School I (Prague, Czech Republic), indicated that there is skepticism in the medical community regarding CIN preventive strategies because of numerous failed approaches, despite that fact that “many surprisingly positive studies with N-acetylcysteine, bicarbonate or ascorbic acid suggested CIN reduction even in randomized, controlled trials.

“Thus, the authors of this study should be congratulated, but the results should be confirmed by a statistically robust, international randomized trial,” he said. “At the moment I personally believe that the cornerstone of CIN prevention is adequate pre-PCI hydration.”

 

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Source:
Patti G, Ricottini E, Nusca A, et al. Short-term, high-dose atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [Atorvastatin for Reduction of MYocardial Damage during Angioplasty-Contrast-Induced Nephropathy] trial. Am J Cardiol. 2011;Epub ahead of print.

 

Disclosures:

• The trial was not supported by any external funding source.
• Dr. Di Sciascio makes no statement regarding conflicts of interest.
• Drs. Solomon and Veselka report no relevant conflicts of interest.

 

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