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Short-Term, High-Dose Atorvastatin Pretreatment to PreventContrast-Induced Nephropathy in Patients With Acute Coronary

Syndromes Undergoing Percutaneous Coronary Intervention (fromthe ARMYDA-CIN [Atorvastatin for Reduction of MYocardial

Damage during Angioplasty–Contrast-Induced Nephropathy] Trial

Giuseppe Patti, MDa, Elisabetta Ricottini, MDa, Annunziata Nusca, MDa, Giuseppe Colonna, MDb,Vincenzo Pasceri, MDc, Andrea D’Ambrosio, MDa, Antonio Montinaro, MDb, and

Germano Di Sciascio, MDa,*

Contrast-induced nephropathy (CIN) impairs clinical outcome in patients undergoingangiographic procedures. The aim of this study was to investigate whether short-termhigh-dose atorvastatin load decreases the incidence of CIN after percutaneous coronaryintervention (PCI). Statin-naive patients with acute coronary syndrome undergoing PCI(n � 241) randomly received atorvastatin (80 mg 12 hours before intervention with another40-mg preprocedure dose, n � 120) or placebo (n � 121). All patients had long-termatorvastatin treatment thereafter (40 mg/day). Primary end point was incidence of CINdefined as postintervention increase in serum creatinine >0.5 mg/dl or >25% from base-line. Five percent of patients in the atorvastatin arm developed CIN versus 13.2% ofthose in the placebo arm (p � 0.046). In the atorvastatin group, postprocedure serumcreatinine was significantly lower (1.06 � 0.35 vs 1.12 � 0.27 mg/dl in placebo, p �0.01), creatinine clearance was decreased (80.1 � 32.2 vs 72.0 � 26.6 ml/min, p �0.034), and C-reactive protein peak levels after intervention were decreased (8.4 � 10.5vs 13.1 � 20.8 mg/l, p � 0.01). Multivariable analysis showed that atorvastatinpretreatment was independently associated with a decreased risk of CIN (odds ratios 0.34,95% confidence interval 0.12 to 0.97, p � 0.043). Prevention of CIN with atorvastatin wasparalleled by a shorter hospital stay (p � 0.007). In conclusion, short-term pretreatmentwith high-dose atorvastatin load prevents CIN and shortens hospital stay in patients withacute coronary syndrome undergoing PCI; anti-inflammatory effects may be involved inthis renal protection. These results lend further support to early use of high-dose statins asadjuvant pharmacologic therapy before percutaneous coronary revascularization. © 2011

Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:1–7)

Pathogenesis of contrast-induced nephropathy (CIN) in-cludes inflammatory mechanisms, endothelial dysfunction,and oxidative stress.1,2 Short-term statin pretreatment hasmproved clinical outcome through lipid-lowering indepen-ent “pleiotropic” effects in various clinical settings such asrevention of periprocedural myocardial damage duringercutaneous coronary intervention (PCI)3–6 or decrease ofostoperative atrial fibrillation after cardiac surgery.7 These

are the rationales for clinical investigations concerning useof statins to prevent CIN. A previous observational nonran-domized study from our institution demonstrated that pa-

aDepartment of Cardiovascular Sciences, Campus Bio-Medico Univer-sity, Rome, Italy; bDepartment of Interventional Cardiology, Vito FazziHospital, Lecce, Italy; cDepartment of Interventional Cardiology, San Fil-ppo Neri Hospital, Rome, Italy. Manuscript received January 14, 2011;evised manuscript received and accepted March 3, 2011.

*Corresponding author: Tel: 39-06-225-411-612; fax: 39-06-225-411-38.

E-mail address: g.disciascio@unicampus.it (G. Di Sciascio); g.patti@

nicampus.it (G. Patti).

002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved.oi:10.1016/j.amjcard.2011.03.001

tients on long-term statin therapy at the time of PCI hadlower occurrence of postprocedure CIN versus statin-naïvepatients8; however, those patients received a multitude ofstatins at variable doses and different durations of therapy.Thus, the Atorvastatin for Reduction of MYocardial Dam-age during Angioplasty–Contrast-Induced Nephropathy(ARMYDA-CIN) trial was designed to test in a randomizedprotocol the hypothesis of whether a specific short-termpretreatment with high-dose atorvastatin decreases the inci-dence of CIN in patients with acute coronary syndromes(ACSs) undergoing early PCI.

Methods

The ARMYDA-CIN trial (Figure 1) is a randomized,multicenter, prospective, double-blind clinical trial per-formed in 2 Italian institutions (Campus Bio-Medico, Uni-versity of Rome and Vito Fazzi Hospital, Lecce). Statin-naive patients with non–ST-segment elevation ACS(unstable angina or non–ST-segment elevation myocardialinfarction) and a planned invasive strategy within 48 hours

were included. Exclusion criteria were current or previous

www.ajconline.org

study. N

2 The American Journal of Cardiology (www.ajconline.org)

(�3 months) statin treatment, non–ST-segment elevationACS with high-risk features warranting emergency coro-nary angiography (�2 hours), any baseline increase in liverenzymes (aspartate aminotransferases/alanine aminotrans-ferases), left ventricular ejection fraction �30%, renal fail-ure with a creatinine level �3 mg/dl, and a history of liveror muscle disease. In total 1,318 patients fulfilling the en-rollment criteria were initially included; 1,048 patients werethen excluded because of current or previous statin treat-ment (n � 801), indication to emergency coronary angiog-raphy (n � 92), low ejection fraction (n � 88), liver/muscledisease (n � 52), or severe renal failure (n � 15). Eligiblepatients were randomly allocated to receive placebo or ator-vastatin (80-mg loading dose given a mean 12 hours beforecoronary angiography with another 40-mg dose approxi-mately 2 hours before the procedure). Patients were as-signed to the study arm using an electronic spreadsheetindicating the group assignment by random numbers; ran-domization blocks were created and distributed to the 2centers. After diagnostic angiography, 29 patients who didnot receive percutaneous revascularization were excluded(13 for indication to medical therapy and 16 to bypasssurgery); thus, 241 patients (120 randomized to atorvastatin

Figure 1. Design of ARMYDA-CIN

and 121 to placebo) undergoing PCI immediately after cor-

onary angiography were enrolled and represent the studypopulation. Physicians performing the procedure and fol-low-up assessment were not aware of the randomizationassignment. Informed consent was obtained in all patients.The study was approved by the institutional review boardsof the institutions involved. The trial was not supported byany external source of funding.

All interventions were performed using a standard tech-nique. All patients received aspirin (100 mg/day) and clopi-dogrel 600-mg load �3 hours before the procedure. Proce-dural success was defined as postprocedure Thrombolysis InMyocardial Infarction grade 3 flow with decrease of steno-sis to �30% residual narrowing by quantitative coronaryangiographic analysis. All interventions were performedwith a nonionic, low-osmolar (915 mOsm/kg), iodinatedcontrast agent (iobitridol, Xenetix, Guerbet, Roissy CdGCedex, France). Glycoprotein IIb/IIIa inhibitors were ad-ministered at the physician’s discretion. During PCI, bivali-rudin was used instead of unfractionated heparin in patientsconsidered at high bleeding risk (�75 years of age, historyof previous bleeding, low body weight). After the proce-dure, aspirin (100 mg/day) was continued indefinitely,

STE � non–ST-segment elevation.

whereas clopidogrel (75 mg/day) was continued for 1 year.

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3Coronary Artery Disease/Atorvastatin Prevents CIN During PCI

All patients received atorvastatin 40 mg/day after PCI, ir-respective of initial randomization assignment.

By study design blood samples were drawn before and at24 and 48 hours after PCI for measurement of serum cre-atinine, with further determinations after 48 hours if clini-cally indicated; for this study the postprocedure peak valuewas used. Creatinine clearance (CrCl) was calculated by theCockcroft-Gault formula: CrCl � ([140 � age] � weight/serum creatinine � 72) with adjustment for female genderCrClfemale � CrCl � 0.85).9 Patients with pre-existing

renal failure (defined as preprocedural serum creatininelevel �1.5 mg/dl or CrCl �60 ml/min) received intrave-nous hydration with normal saline at 1 ml/hour/kg bodyweight for �12 hours before and �24 hours after interven-tion. No specific protocol for periprocedural use of otherpotentially renal-protective agents was used. Maximal al-lowable weight- and creatinine-adjusted contrast dose wascalculated by the formula: body weight (kilograms) � 5ml/serum creatinine.10 C-reactive protein (CRP) levels weremeasured before PCI and at 24 and 48 hours after interven-tion by the KRIPTOR ultrasensitive immunofluorescenceassay (BRAHMS, Hennigsdorf/Berlin, Germany) with a

Table 1Baseline demographics and clinical features

Characteristic Atorvastatin Placebo p Value(n � 120) (n � 121)

Age (years) 65 � 11 66 � 10 0.46Women 29 (24%) 25 (21%) 0.62

ystemic hypertension 91 (76%) 90 (74%) 0.91iabetes mellitus 36 (30%) 32 (25%) 0.64ypercholesterolemia (�200

mg/dl)31 (26%) 33 (27%) 0.92

igarette smokers 39 (32%) 29 (24%) 0.18ody mass index (kg/m2) 26.9 � 4.3 26.8 � 3.9 0.85linical presentationnstable angina 77 (64%) 82 (68%) 0.65on–ST-segment elevation

myocardial infarction43 (36%) 39 (32%) 0.65

revious myocardial infarction 23 (19%) 22 (18%) 0.97revious coronary intervention 11 (9%) 12 (10%) 0.98revious coronary bypass surgery 4 (3%) 4 (3%) 0.73hronic renal failure 35 (29%) 39 (32%) 0.71erum creatinine (mg/dl) 1.04 � 0.32 1.04 � 0.22 0.96reatinine clearance (ml/min) 79.8 � 29.4 77.0 � 27.6 0.45emoglobin (g/dl) 13.7 � 1.4 13.4 � 1.7 0.14eft ventricular ejection fraction

(%)54 � 9 56 � 8 0.07

ime to angiography (hours) 20 � 10 20 � 11 0.88herapyAspirin 120 (100%) 121 (100%) —Clopidogrel 120 (100%) 121 (100%) —Angiotensin converting enzyme

inhibitors/angiotensin-receptor antagonists

89 (74%) 91 (75%) 0.97

� Blockers 43 (36%) 36 (30%) 0.38Calcium channel blockers 30 (25%) 26 (21%) 0.62Diuretics 15 (13%) 12 (10%) 0.67N-acetylcysteine 5 (4%) 7 (6%) 0.78Sodium bicarbonate 4 (3%) 7 (6%) 0.55

detection limit of 0.06 mg/L. A

The primary end point of the trial was incidence of CINdefined as a postintervention increase in serum creatinine�0.5 mg/dl or �25% from baseline.1 The following out-omes were evaluated as secondary end points: (1) postpro-edure acute renal failure defined as a rapid decrease inenal glomerular filtration with �2 mg/dl creatinine in-rease from baseline; (2) postprocedure levels of serumreatinine and CrCl; (3) percent variation of creatinine andrCl after PCI versus baseline; (4) correlation of CRP peak

evels after PCI with occurrence of CIN; and (5) length oftay after PCI.

If we hypothesize a 15% incidence of CIN in the controlrm and a 66% decrease in the atorvastatin arm,11 a total

sample size of 236 patients (118 in each group) wouldprovide 80% power to detect the difference with an alphalevel of 0.05. Results are expressed as mean � SD unlessotherwise specified. Continuous variables were comparedby t test for normally distributed values; otherwise the

ann–Whitney U test was used. Proportions were com-ared by Fisher’s exact test when the expected frequencyas �5; otherwise chi-square test (Yates corrected) was

pplied. Odds ratios and 95% confidence intervals assessinghe risk of the primary end point according to potentialonfounding variables were assessed by logistic regression.he following parameters were evaluated first in a univar-

ate model: study drug assignment (atorvastatin or placebo),ge, gender, systemic hypertension, diabetes, left ventricu-ar ejection fraction, previous myocardial infarction, therapyith � blockers, angiotensin-converting enzyme inhibitors

nd diuretics, baseline renal failure, baseline CrCl and se-um creatinine, maximal contrast load, and maximal allow-ble contrast dose. Variables with a p value �0.15 werehen entered into multivariable logistic regression analysis.

able 2ngiographic and procedural characteristics

Characteristic Atorvastatin Placebo p Value(n � 120) (n � 121)

Multivessel coronary disease 47 (39%) 57 (47%) 0.26Multivessel intervention 28 (23%) 30 (25%) 0.91Coronary vessel treated

Left main 1 (1%) 1 (1%) 0.49Left anterior descending 69 (46%) 66 (44%) 0.70Left circumflex 44 (30%) 41 (27%) 0.71Right 31 (21%) 41 (27%) 0.26Saphenous vein grafts 3 (2%) 2 (1%) 0.98

Lesion B2/C 103 (86%) 102 (84%) 0.88Type of procedure

Balloon only 3 (2%) 1 (1%) 0.61Stent 117 (98%) 120 (99%) 0.61

Use of drug-eluting stents 54 (45%) 47 (39%) 0.40Total stent length (mm) 15.7 � 4.6 15.1 � 4.8 0.32Periprocedural antithrombotic

therapyGlycoprotein IIb/IIIa inhibitors 27 (23%) 23 (19%) 0.61Unfractionated heparin 116 (97%) 117 (97%) 0.73Bivalirudin 4 (3%) 4 (3%) 0.73Total mean contrast volume (ml) 209 � 72 213 � 13 0.67Exceeding maximal allowable

contrast dose20 (17%) 16 (13%) 0.57

ll calculations were performed by SPSS 12.0 (SPSS, Inc.,

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4 The American Journal of Cardiology (www.ajconline.org)

Chicago, Illinois) and p values �0.05 (2-tailed) were con-sidered statistically significant.

Results

Clinical and procedural characteristics were similar inthe 2 arms and are presented in Tables 1 and 2, respectively.In particular, the proportion of diabetes mellitus was 30% inthe atorvastatin and 25% in the placebo group (p � 0.64),nd that of chronic renal failure was 29% and 32% (p � 0.71);aseline serum creatinine and CrCl values were 1.04 � 0.32ersus 1.04 � 0.22 mg/dl (p � 0.96) and 79.8 � 29.4 versus

77.0 � 27.6 ml/min (p � 0.45), respectively. Mean timefrom admission to angiography was 20 hours and proce-dural success was achieved in all patients; mean proceduralcontrast volume was not different in the 2 groups (atorva-statin 209 � 72 ml vs placebo 213 � 73 ml, p � 0.67), norwas the proportion of patients exceeding the maximal al-lowable contrast dose (17% vs 13%, p � 0.57).

Incidence of CIN was significantly lower in patientsrandomized to atorvastatin (5%, 6 of 120, vs 13.2%, 16 of121, in placebo arm, p � 0.046; Figure 2). Patients withCIN had received a larger contrast load versus those withoutCIN (240 � 77 vs 208 � 72 ml, p � 0.042). In the subgroup

Figure 2. Incidence of contrast-induced nephropathy (A) and periproceduralars) arms.

Figure 3. Postprocedure C-reactive protein peak levels (A) in the 2

without baseline chronic renal failure, incidence of CIN was

1% in the atorvastatin versus 7% in the placebo group (oddsratio 0.15, 95% confidence interval 0.01 to 1.31, p � 0.11),whereas in patients with chronic renal failure it was 14%versus 26% (odds ratio 0.48, 0.12 to 1.80, p � 0.36).

Postprocedure acute renal failure occurred in 1 patient inthe placebo group, who was successfully treated with ultra-filtration. Patients with CIN or acute renal failure weredischarged when renal function returned to baseline afteraggressive hydration.

Postprocedure levels of serum creatinine were signifi-cantly lower in the atorvastatin arm (1.06 � 0.35 vs 1.12 �0.27 mg/dl in placebo group, p � 0.01), and CrCl was lower(80.1 � 32.2 vs 72.0 � 26.6 ml/min, p � 0.034; Figure 2).After PCI percent variation of creatinine and CrCl frombaseline were also improved in the active treatment armversus placebo (creatinine �2.4 � 23.6% vs �8.2 �15.0%, p � 0.024; CrCl �1.1 � 19.4% vs �6.0 � 12.3%,p � 0.001).

Baseline preoperative CRP levels were not different(5.4 � 8.1 mg/L in atorvastatin group vs 6.3 � 10.8 mg/Lin placebo group, p � 0.90), whereas CRP peak levels afterthe intervention were lower in the atorvastatin arm (8.4 �10.5 vs 13.1 � 20.8 mg/L, p � 0.01). Postprocedure CRP

ine clearance values (B) in the atorvastatin (black bars) and placebo (white

and (B) according to occurrence of contrast-induced nephropathy.

creatin

levels were higher in patients with CIN (22.4 � 35.5 vs

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5Coronary Artery Disease/Atorvastatin Prevents CIN During PCI

9.6 � 13.0 mg/L in those without, p � 0.006) irrespectivef randomization assignment (Figure 3); in the subgroupithout CIN, CRP peak levels after PCI were significantly

ttenuated in the atorvastatin arm (7.7 � 9.2 vs 11.7 � 15.9mg/L in placebo arm, p � 0.015).

Length of stay after intervention was shorter in patientsrandomized to atorvastatin (2.9 � 0.9 vs 3.2 � 0.8 days,

� 0.007) and longer in patients with CIN (3.5 � 0.9 vs.9 � 0.7 days in those without CIN, p � 0.001).

Multivariable analysis (Figure 4) revealed that atorvasta-in pretreatment was independently associated with de-reased risk of CIN (odds ratio 0.34, 0.12 to 0.97, p �.043); age �65 years and exceeding the maximal allow-ble contrast dose were predictors of increased risk.

iscussion

The randomized placebo-controlled ARMYDA-CIN trialemonstrates that short-term pretreatment with high-dosetorvastatin significantly decreases the occurrence of CIN intatin-naive patients with ACS receiving early PCI.

The incidence of CIN differs widely across publishedtudies depending on patients’ risk profile and prevalence ofactors potentially predisposing to such complication suchs advanced age, diabetes mellitus, congestive heart failure,nd pre-existing impaired renal function.1,12–14 Develop-

ment of CIN after PCI in patients with normal renal functionor further renal function deterioration in those with chronicrenal failure is associated with an adverse outcome includ-ing more in-hospital events and higher risk of late cardio-vascular events and mortality.1,12–14 Thus, prevention ofCIN may translate into improved clinical outcome duringfollow-up.

Various mechanisms are involved in the pathogenesis ofCIN; in particular, soon after contrast exposure there ismedullar hypoxia because of adenosine production from themacula densa, release of angiotensin, vasopressin, and en-dothelin, and decreased synthesis of nitric oxide.1,2 Later,ther organ injury processes may take place including oxi-ative stress, release of proinflammatory cytokines andomplement activation, with subsequent cytoplasmic vacu-lization, necrosis, interstitial inflammation, and tubular ob-truction by protein precipitates.1,2,15 Statins may protect

Odds Ratios for contrast-

Age >65 years

Exceeding maximumcontrast dose

Contrast load

Atorvastatin

0 1 3

Figure 4. Multivariable analysis for contrast-induced

he kidney acting at different stages of the pathogenetic

echanisms of CIN: by downregulating angiotensin recep-ors,16 decreasing endothelin synthesis,17 increasing nitricxide bioavailability,17 attenuating inflammation,18 decreas-ng expression of endothelial adhesion molecules,4 limiting

reactive oxygen species production,19 and protecting againstomplement-mediated injury.20 Moreover, experimental

data have shown that statins may exert nephrotic protectiveeffects in a rat model of long-term inhibition of nitric oxidesynthesis by amelioration of vascular endothelial growthfactor expression and decrease of RhoA activity.21

Previous studies have evaluated the possible role of st-atins to prevent renal deterioration in patients undergoingdiagnostic or therapeutic angiographic procedures; observa-tional reports on this topic have described conflicting re-sults,22–26 and randomized studies were underpowered forncidence of CIN27,28 or investigated only patients withhronic renal failure.29,30 Recent data have indicated thattorvastatin 80 mg does not decrease the incidence of CINn patients with chronic kidney disease28,30; thus atorvasta-in load may not have the same effects in all situations. Inact, a previous study from the ARMYDA study groupbserved no CIN decrease in statin-treated versus statin-aive patients with a baseline CrCl �40 ml/min,8 probably

because of multiple nonreversible pathogenetic mechanismsinvolved in advanced renal failure. ARMYDA-CIN in-cluded patients with normal and impaired baseline renalfunction unless this was severe (serum creatinine �3 mg/dl); this study demonstrated in patients with ACS a 66%relative decrease of CIN with 12 hours of pretreatment ofatorvastatin 80 � 40 mg before PCI, with a number neededto treat of 12. This benefit was paralleled by an attenuationof a postprocedure creatinine increase versus placebo; ofnote, CrCl after contrast exposure decreased in the controlgroup but remained essentially unchanged in the atorvasta-tin arm. Our study also confirmed that older age and in-creased contrast load, adjusted for weight and baseline renalfunction, are associated with higher risk of CIN; the averagecontrast volume per patient was relatively high, reflectingthe choice to perform PCI immediately after diagnosticangiography. Moreover, high-dose atorvastatin decreasedthe length of stay through prevention of renal functiondeterioration after contrast exposure. In our previous obser-

ed nephropathy

4.4 (1.2-15.7) 0.023

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0.34 (0.12-0.97) 0.043

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OR (95% CI) P

pathy. CI � confidence interval; OR � odds ratio.

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vational study CIN was associated with an absolute increase

2

6 The American Journal of Cardiology (www.ajconline.org)

of cardiac events of 26% at 4 years8; according to thesedata, an absolute CIN decrease of 8%, as observed inARMYDA-CIN, would translate into 8 major adverse car-diac events avoided for 1,000 patients treated in 1 year.Further studies are warranted to evaluate the relative benefitof statin pretreatment on CIN prevention in the context ofother pharmacologic therapies (sodium bicarbonate, N-ace-tylcysteine) that in clinical studies significantly decreasedthe incidence of such complications.1,31

In our study patients developing CIN had higher CRPpeak levels after PCI and prevention of CIN by pretreat-ment with atorvastatin was paralleled by a significantdecrease of postintervention CRP levels. Thus, thesefindings confirm that inflammatory mechanisms may beinvolved in the pathogenesis of CIN and that renal pro-tection by atorvastatin after PCI is probably due to theirattenuation, although other pleiotropic effects may beresponsible. Patients with ACS have a high inflammatorystatus and ongoing endothelial dysfunction; thus, theymay derive the greatest benefit from early high-dosestatin therapy before an invasive strategy in renal andmyocardial protection, as previously demonstrated in theARMYDA-ACS trial.5 However, ARMYDA-CIN in-cluded only statin-naive patients; thus, prevention of CINby a high-dose statin load might be less pronounced inpatients treated long term with statins.

1. McCullough PA. Contrast-induced acute kidney injury. J Am CollCardiol 2008;51:1419–1428.

2. Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N,McCullough PA, on behalf of the CIN Consensus Working Panel.Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006;98(suppl):14K–20K.

3. Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G.Randomized trial of atorvastatin for reduction of myocardial damageduring coronary intervention: Results from the ARMYDA (Atorvasta-tin for Reduction of MYocardial Damage during Angioplasty) study.Circulation 2004;110:674–678.

4. Patti G, Chello M, Pasceri V, Colonna D, Nusca A, Miglionico M,D’Ambrosio A, Covino E, Di Sciascio G. Protection from proceduralmyocardial injury by atorvastatin is associated with lower levels ofadhesion molecules after percutaneous coronary intervention: resultsfrom the ARMYDA-CAMs (Atorvastatin for Reduction of MYocar-dial Damage during Angioplasty–Cell Adhesion Molecules) substudy.J Am Coll Cardiol 2006;48:1560–1566.

5. Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G,Montinaro A, Di Sciascio G. Atorvastatin pretreatment improves out-comes in patients with acute coronary syndromes undergoing earlypercutaneous coronary intervention: results of the ARMYDA-ACSrandomized trial. J Am Coll Cardiol 2007;49:1272–1278.

6. Di Sciascio G, Patti G, Pasceri V, Gaspardone A, Colonna G, Mon-tinaro A. Efficacy of atorvastatin reload in patients on chronic statintherapy undergoing percutaneous coronary intervention: results of theARMYDA-RECAPTURE (Atorvastatin for Reduction of MyocardialDamage During Angioplasty) randomized trial. J Am Coll Cardiol2009;54:558–565.

7. Patti G, Chello M, Candura D, Pasceri V, D’Ambrosio A, Covino E,Di Sciascio G. Randomized trial of atorvastatin for reduction of post-operative atrial fibrillation in patients undergoing cardiac surgery:results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardialDysrhythmia After cardiac surgery) study. Circulation 2006;114:1455–1461.

8. Patti G, Nusca A, Chello M, Pasceri V, D’Ambrosio A, Vetrovec GW,Di Sciascio G. Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patientsundergoing percutaneous coronary intervention. Am J Cardiol 2008;

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