ARMYDA-CIN Trial [Atorvastatin for Reduction of Myocardial Damage during Angioplasty–Contrast-Induced Nephropathy]

AIM : whether short-term high-dose atorvastatin load decreases the incidence of CIN after percutaneous coronary intervention (PCI).

Randomised,multicentre,prospective,double blind trial ….2 Italian institutions. INCLUSION CRITERIA Statin naïve patients with ACS(UA/NSTEMI) & a planned invasive strategy with in 48 hrs EXCLUSION CRITERIA on statin/was on statin (<3m) NSTE high risk pts needing emergency CAG (<2hrs) Baseline elevated liver enzymes (AST/ALT) LVEF<30% Renal failure with creatinine >3 mg/dl h/o renal or liver disease

Procedures….standard technique All patients received aspirin (100 mg/day) and clopidogrel 600-mg load 3 hours before the procedure Nonionic low osmolar iodinated contrast agent (iobitridol, Xenetix, Guerbet) … Maximum allowable dose : body weight (kilograms) X 5ml/serum creatinine Aspirin 100 mg….indefinitely Clopidogrel 75 mg for 1 yr ALL patients … statin 40 mg after the procedure Other drugs…. Bivalirudin, GpIIbIIIa inhib..

Blood samples…for creatinine,CRP…before; at 24 hrs; at 48 hrs of the procedure…& after 48 hrs if clinically indicated…Peak post procedural values were taken Pre existing renal failure?(Creat>1.6/CrCl 12hrs prior & >24 hrs post procedure.

Primary end point : Incidence of CIN … post procedure rise in creat >0.5 or >25% from baseline. Secondary outcomes evaluated : Post procedure ARF (Cr rise >2mg/dl from the baseline value) Post proced levels of serum creatinine & CrCl percent variation of creatinine and CrCl after PCI versus baseline; correlation of CRP peak levels after PCI with occurrence of CIN; length of stay after PCI.

RESULTS : Incidence of CIN was significantly lower in patients randomized to atorvastatin (5%, 6 of 120, vs 13.2%, 16 of 121, in placebo arm, p 0.046). Patients with CIN had received a larger contrast load versus those without CIN ( vs ml, p 0.042). In the subgroup without baseline CRF, incidence of CIN was 1% in the atorvastatin versus 7% in the placebo group (odds ratio 0.15, 95% confidence interval 0.01 to 1.31, p 0.11) In patients with CRF, it was 14% versus 26% (odds ratio 0.48, 0.12 to 1.80, p 0.36).

Postprocedure levels of serum creatinine were significantly lower in the atorvastatin arm ( vs mg/dl in placebo group, p 0.01), and CrCl was better in the drug arm ( vs ml/min, p 0.034) After PCI percent variation of creatinine and CrCl from baseline were also improved in the active treatment arm versus placebo (creatinine % vs %, p 0.024; CrCl % vs %,p 0.001).

Length of stay after intervention was shorter in patients randomized to atorvastatin ( vs days, p 0.007) and longer in patients with CIN ( vs days in those without CIN, p 0.001).

So….Short-term pretreatment with high-dose atorvastatin significantly decreases the occurrence of CIN in statin- naive patients with ACS receiving early PCI.

STATINS : MOA : downregulates angiotensin receptors, decreases endothelin synthesis, increasing NO bioavailability, attenuating inflammation, Decreases expression of endothelial adhesion molecules, Limiting reactive oxygen species production, protects against complement-mediated injury

Previous observational study[by same group]….CIN a/w an absolute increase in cardiac events of 4 yrs. So…..an absolute CIN decrease of 8%, as observed in ARMYDA-CIN, would translate into 8 MACEs avoided for 1,000 patients treated in 1 year.

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