DOI: 10.1016/j.athoracsur.2007.05.021 2007;84:1158-1164 Ann Thorac Surg

Tozzi, Davide Vanoli, Bruno Vito Domenico and Andrea Sala Giovanni Mariscalco, Roberto Lorusso, Catherine Klersy, Sandro Ferrarese, Matteo

Atrial Fibrillation After Coronary SurgeryObservational Study on the Beneficial Effect of Preoperative Statins in Reducing

http://ats.ctsnetjournals.org/cgi/content/full/84/4/1158located on the World Wide Web at:

The online version of this article, along with updated information and services, is

Print ISSN: 0003-4975; eISSN: 1552-6259. Southern Thoracic Surgical Association. Copyright © 2007 by The Society of Thoracic Surgeons.

is the official journal of The Society of Thoracic Surgeons and theThe Annals of Thoracic Surgery

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bservational Study on the Beneficial Effect ofreoperative Statins in Reducing Atrial Fibrillationfter Coronary Surgery

iovanni Mariscalco, MD, Roberto Lorusso, MD, PhD, Catherine Klersy, MD, MS,andro Ferrarese, MD, Matteo Tozzi, MD, Davide Vanoli, MD,runo Vito Domenico, MD, and Andrea Sala, MDepartment of Surgical Sciences, Cardiac Surgery Unit, Varese University Hospital, University of Insubria, Varese; Cardiacurgery Unit, Civic Hospital, Brescia; Service of Biometry and Clinical Epidemiology, Scientific Direction, IRCCS Fondazioneoliclinico San Matteo, Pavia; Department of Surgical Sciences, Vascular Surgery Unit, Varese University Hospital, University of

nsubria, Varese, Italy

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Background. Recent evidence supports the importantole of inflammation in atrial fibrillation (AF) after coro-ary artery bypass grafting (CABG) and there is growingvidence that statin has cardiac antiarrhythmic effects.he aim of this study was to assess the efficacy ofreoperative statins in preventing AF after CABG in a

ongitudinal observational study.Methods. Over a two-year period, 405 consecutive pa-

ients underwent isolated CABG procedures. Univariatenalysis was performed exploring the relationshipegarding statin use and AF development. A propen-ity score for treatment with statins was obtained fromore patient characteristics. The role of statin therapyn postoperative AF was assessed by means of aonditional logistic model, while stratifying on theuintiles of the propensity score. All analysis was

erformed retrospectively.

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nces, Cardiac Surgery Division, Varese University Hospital, Varese,-21100, Italy; e-mail: giovannimariscalco@yahoo.it.

2007 by The Society of Thoracic Surgeonsublished by Elsevier Inc

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Results. Postoperative AF occurred in 29.5% of theatients with preoperative statin therapy compared with0.9% of those patients without it (p � 0.021). No statis-ical differences among development of AF and type,ose, or duration of preoperative statin therapy werebserved. Preoperative statins were associated with a2% reduction in risk of AF development after CABGurgery (odds ratio [OR] 0.58, 95% confidence intervalCI] 0.37 to 0.91, p � 0.017, while stratifying on theropensity score). No different effect of statins on AF wasbserved with respect to age groups (< 70 and >70 years)interaction p � 0.711).

Conclusions. Preoperative statins may reduce postopera-ive AF after CABG. Patients undergoing elective revascu-arization may benefit from a preventive statin approach.

(Ann Thorac Surg 2007;84:1158–65)

© 2007 by The Society of Thoracic Surgeons

trial fibrillation (AF) is the most common complica-tion after cardiac surgery, with important clinical

nd economic implications [1, 2]. Although several stud-es have identified various baseline predictors of postop-rative AF, the pathophysiologic mechanisms remainnclear [1]. Observational evidences seemed to testify an

nflammatory component of this postoperative arrhyth-ia [3, 4]. Statin drugs, which have both antioxidant and

ntiinflammatory properties, may attenuate postopera-ive AF development and constitute a potential preven-ive approach [5]. Patients with preoperative statins un-ergoing cardiac surgery demonstrated a lower

ncidence of postoperative AF [6–8].Therefore, the purpose of the present study was to

valuate the influence of preoperative statin therapy onF development after coronary artery bypass grafting

CABG). The identification of further operative and post-

ccepted for publication May 7, 2007.

ddress correspondence to Dr Mariscalco, Department of Surgical Sci-

perative determinants of AF was evaluated as a second-ry endpoint.

atients and Methods

atients and Study Designver a two-year period (2005 to 2006), all consecutiveatients scheduled for primary isolated CABG (n � 422)ere considered for the study. Patients with permanentacemaker (n � 5), chronic AF (n � 7), or inflammatoryiseases that required therapy with steroids or nonste-oidal antiinflammatory drugs (n � 5), were subse-uently excluded. Thus, 405 patients represented thetudy population; 320 (79%) were operated on cardiopul-onary bypass (CPB) and 85 (21%) underwent off-pumpABG. The study cohort had an average age of 66.1 � 9.4ears (range, 34 to 85 years) and contained 81% men.emographic data are listed in Table 1.Although all data were prospectively recorded into the

ospital computerized database registry that remainedonsistent over the study period, this is an observational

etrospective study. The database registry captures 100%

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1159Ann Thorac Surg MARISCALCO ET AL2007;84:1158–65 STATINS AND POSTOPERATIVE ATRIAL FIBRILLATION

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f cardiac surgeries performed at Varese University Hos-ital and is validated by random audits of patient charts.ata entry is managed by surgeons, anesthetists, anderfusionists involved in the care of the patients. Core-ata input had a “check-in–check-out” character at timesf admission, operation, intensive care unit, and at dis-harge or subsequent clinical visits, whereas other obser-ations (such as atrial fibrillation) are entered on a dailyasis and confirmed at “check-out.”

ata Definitionsll variables analyzed in the study are listed in theppendix. Preoperative patient characteristics were eval-ated after current guidelines. In particular, hyperten-ion was considered according to the Joint Nationalommittee VI, diabetes mellitus according to the Amer-

can Diabetes Association, and dyslipidemia according tohe National Cholesterol Education Program–Adult

able 1. Clinical Characteristics of the Population Study andibrillation

ariables UnitStatin

(n � 218) p V

emographicsAge [y] 65.5 � 9.1 0Females [%] 16.6 0BMI [Kg/m2] 26.8 � 3.8 0

ardiacUnstable [%] 22.1 0CCS [1–4] 3.1 � 0.9 0History of AF [%] 5.5 0Prior AMI [%] 64.1 0Prior PCI [%] 11.8 0LVEF [%] 53.6 � 11.0 0LA AP dimension [mm] 38.4 � 5.3 0LMCA stenosis [%] 29.8 0RCA stenosis [%] 65.6 0

omorbiditiesHypertension [%] 70.5 0Diabetes [%] 31.5 0Dyslipidemia [%] 50.5 0COPD [%] 8.8 0PVD [%] 13.0 0CVA [%] 5.6 0Renal failure [%] 5.6 0Euroscore [score] 4.0 � 2.3 0

reoperative medications�-blockers [%] 66.2 0Ca-antagonists [%] 25.8 0ACE-Inhibitors [%] 55.4 0Statins [%] n.a.

ata are mean � SD or pecentages.

CE � angiotensin-converting enzyme; AF � atrial fibrillation; Aanadian Cardiovascular Society angina classification; Ca-antagonisisease; CVA � cerebrovascular accident; LA � left atrial diamete

raction; PVD � peripheral vascular disease; RCA � right corona

reatment Panel II criteria [9–11]. Angina was defined by r

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he Canadian Cardiovascular Society Classification [12].hronic obstructive pulmonary disease (COPD), periph-ral vascular disease, and renal failure were definedccording to the European system for cardiac operativeisk evaluation [13]. The latest was also considered touantify the preoperative surgical risk [13].The study was approved by our Institutional Review

oard (protocol nr.117) and, because of its retrospectiveature, individual patient consent was waived. The studyas also not supported by any external source of

unding.

linical Management and AF Definitionll patients were subjected to preoperative coronaryngiography, transthoracic echocardiography, and color-oppler ultrasound of epiaortic vessels. Preoperativeedications, including �-blockers, diuretics, antihyper-

ensives, statins, and calcium-channel blockers, were

tionship With Statin Use and Postoperative Atrial

No Statin(n � 187)

AF(n � 141) p Value

No AF(n � 264)

65.5 � 9.7 70.5 � 8.0 �0.001 63.7 � 9.221.0 22.7 0.139 16.3

26.6 � 3.7 26.3 � 3.9 0.165 26.9 � 3.6

24.7 21.3 0.464 24.63.1 � 1.0 3.1 � 1.0 0.678 3.1 � 1.0

5.4 10.6 0.002 2.752.7 62.1 0.340 56.818.4 12.9 0.384 16.7

53.7 � 11.6 51.8 � 11.4 0.025 54.6 � 11.138.1 � 4.7 37.6 � 6.2 0.450 38.5 � 4.2

32.3 30.2 0.821 31.664.5 68.3 0.324 63.1

73.0 72.1 0.818 70.828.1 33.1 0.305 28.138.7 39.6 0.107 48.48.1 12.2 0.059 6.5

20.5 19.4 0.325 15.37.6 6.5 0.999 6.54.9 5.3 0.999 5.0

4.2 � 2.8 4.9 � 2.5 �0.001 3.6 � 2.4

73.1 70.6 0.420 66.427.8 28.9 0.473 25.551.7 57.8 0.242 51.4n.a. 45.7 0.021 58.2

acute myocardial infarction; BMI � body mass index; CCS �calcium channel blockers; COPD � chronic obstructive pulmonaryLMCA � left main coronary artery; LVEF � left ventricular ejection

ery.

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.151

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outinely omitted on the day of the operation and re-

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1160 MARISCALCO ET AL Ann Thorac SurgSTATINS AND POSTOPERATIVE ATRIAL FIBRILLATION 2007;84:1158–65

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tarted after the operation, unless clinically contraindi-ated. Commercially available statins screened for in thistudy were atorvastatin, pravastatin, simvastatin, lova-tatin, rosuvastatin, and fluvastatin.

All patients were daily monitored until discharge withontinuous electrocardiographic telemetry, as well astandard 12-lead electrocardiography. Additional record-ngs were collected at clinical suspicion of AF. Only AFpisodes lasting longer than 15 minutes were considered14]. Atrial flutter or tachycardia were disregarded be-ause of their different mechanisms [15]. Amiodarone,ither oral or intravenously administered, constituted thetandard pharmacologic treatment of AF. Patients with-ut successful rhythm cardioversion and with persistentF were given warfarin and were discharged to the

eferring hospital, with a planned electric cardioversionithin thirty days.

urgical Techniques and Operative Managementll procedures were performed through a median ster-otomy approach, using either an on-pump or off-pump

echnique. The anesthetic management followed identi-al routine methods. Cardiopulmonary bypass was oftandardized fashion, with ascending aortic cannulationnd two-stage venous cannulation of the right atrium.he CPB was conducted using a membrane oxygenatorith hemodilution and mild systemic hypothermia. Myo-

ardial protection was afforded by intermittent cardiople-ia (crystalloid or blood, antegrade or retrograde routes).Off-pump procedures were conducted using the CTS

tabilization system (Guidant, Santa Clara, CA) at nearormothermia. Intracoronary shunts were used when-ver possible.To reduce blood loss, blood was recollected with a

able 2. Operative and Postoperative Variables With Relation

ariables UnitStatin

(n � 218) V

perative factorsOn-pump procedures [%] 76.0 0Grafts [n] 2.8 � 0.8 0CPB-time [min] 84.7 � 37.8 0ACC-time [min] 53.1 � 21.7 0IABP [%] 2.3 0

ostoperative dataInotropic drugs [%] 68.7 0Respiratory failure [%] 12.4 0Perioperative AMI [%] 5.9 0Reoperation for bleeding [%] 3.8 0Ventilation time [h] 24.1 � 60.4 0ICU stay [h] 42.4 � 69.0 0LOS [days] 7.8 � 4.0 0Hospital mortality [%] 0.0 0

ata are mean � SD or pecentages.

CC � aortic cross clamp; AF � atrial fibrillation; AMI � acute myalloon pump; ICU � intensive care unit; LOS � lenght of hospi

uction cardiotomy reservoir in the CPB group, whereas A

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cell saver was used in the off-pump group. All proce-ures had the left internal mammary artery supplying

he left anterior descending artery. Other conduits in-luded the right internal mammary artery, radial artery,nd saphenous vein, as found appropriate. Proximalnastomoses were performed using a side-biting clamp.After surgery, patients were transferred to a dedicated

ardiovascular intensive care unit (ICU). Heart rate, elec-rocardiogram, central venous and arterial pressures, andcid-base and blood gases were continuously monitoreduring the ICU stay. Inotropic support was provided if

he ventricular contractility was considered frankly im-aired in order to achieve stable hemodynamic condi-

ions. Perioperative need for blood products was deter-ined on an individual, patient-by-patient basis; in

eneral, blood transfusions were administered whenemoglobin was less than 9 g/dL. Fluid intake and outputere monitored hourly throughout the hospital stay.

tatisticslinical data were prospectively recorded and tabulatedith Microsoft Excel (Microsoft Corp, Redmond, WA).

With Statin Use and Postoperative Atrial Fibrillation

No Statin(n � 187)

AF(n � 141)

pValue

no AF(n � 264)

82.8 78.7 0.999 79.22.9 � 0.8 2.9 � 0.7 0.316 2.8 � 0.9

88.6 � 29.9 88.2 � 31.0 0.522 85.6 � 35.853.5 � 18.8 52.5 � 15.6 0.621 53.6 � 22.3

5.9 7.1 0.029 2.3

73.7 73.0 0.492 69.39.3 15.0 0.065 8.75.1 3.6 0.356 6.53.2 3.6 0.999 3.4

30.1 � 46.5 33.0 � 75.9 0.105 23.5 � 36.747.1 � 53.3 52.9 � 86.5 0.112 40.1 � 42.48.4 � 4.7 8.2 � 3.2 0.575 8.0 � 4.8

0.5 0.7 0.348 0.0

ial infarction; CPB � cardiopulmonary bypass; IABP � intraaorticy.

able 3. Postoperative Atrial Fibrillation Features and Statinse

vent UnitAll

Patients Statinsp

ValueNo

Statins

F occurrence [%] 34.8 29.5 0.021 40.9F, days aftersurgery

[days] 2.1 � 0.9 2.1 � 0.8 0.683 2.1 � 1.0

F recurrence [%] 21.5 16.4 0.202 26.5F at discharge [%] 6.1 4.9 0.723 7.1

ship

palue

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.311

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.075

.322

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.827

.791

.283

.473

.134

.999

F � postoperative atrial fibrillation.

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ontinuous variables were tested for normal distributiony the Kolmogorov-Smirnov test and compared betweenroups with the unpaired Student ttest for normallyistributed values; otherwise the Mann-Whitney Utestas employed. In case of dichotomous variables, groupifferences were examined by �2 or Fisher exact tests asppropriate.The likelihood of receiving a preoperative treatmentith statins was taken into account by computing aropensity score (by means of a logistic model) based on

he preoperative characteristics listed in Table 1. The rolef statin therapy on postoperative AF occurrence (pri-ary endpoint) was assessed by means of a conditional

ogistic model, while stratifying on the quintiles of theropensity score [16]. Further, the modifying effect of age

�70 and �70 years) was assessed by including annteraction term in the model. As a secondary endpoint,otential operative and postoperative determinants of AFere also fitted in the model to assess their prognostic

ole. These included noncollinear clinically relevant vari-bles, with a pvalue less than 0.15 at the univariatenalysis. Kaplan-Meier cumulative AF-free survival wasomputed according to statin treatment and plotted.esults are expressed as mean � SD for continuousariables and frequencies for the categoric ones.A two-sided pvalue less than 0.05 was considered

tatistically significant. Statistical analysis was performedith Stata 9.2 (StataCorp, College Station, TX) and withPSS, release 13.0 for Windows (SPSS Inc, Chicago, IL).

esults

nivariate Analysisnivariate analyses regarding statin use and AF occur-

ence are represented in Tables 1 and 2.The overall incidence of AF in the study populationas 34.8%. Postoperative AF occurred in 29.5% of theatients with preoperative statin therapy compared with0.9% of those without it (p � 0.021).

The use of calcium-channel blockers, of angiotensin-onverting enzyme-inhibitors, and of �-blockers did notnfluence the AF development (Table 1). In detail, pa-ients with preoperative �-blocker therapy comparedith patients without it demonstrated similar AF rates

33.1% vs 37.5%, p � 0.420). However, withdrawal from

able 4. Statin Characteristics and Postoperative Atrial Fibril

ariable Unit All Patients

ypeSinvastatin [%] 44.2Atorvastatin [%] 37.7Othersa [%] 18.2ose [mg/die] 21.7 � 10.0uration [days] 45.5 � 22.0

Pravastatin, lovastatin, rosuvastatin, and fluvastatin (grouped).

F � postoperative atrial fibrillation.

reoperative �-blocker therapy was significantly associ- 0

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ted with a new-onset of AF (45.1% vs 31.6%, p � 0.027).o surgical variables, with the exception of postoperative

ntraaortic balloon pump (IABP) requirement, wereound associated with postoperative AF (Table 2). Also,o differences were evident concerning the modality ofevascularization. Postoperative AF occurred in 11134.7%) of 320 patients operated on CPB versus 30 (35.3%)f 85 patients subjected to off-pump revascularizationp � 0.999).

No differences were observed between patients withreoperative statins and patients without them, with thexception of patients affected by dyslipidemia and previ-us myocardial infarction (p � 0.023 and p � 0.025,espectively). In particular, the time of AF occurrence, AFecurrence, and the persistence of the arrhythmia atischarge were not influenced by statin use (Table 3).ithdrawal from preoperative statin therapy occurred in

1 patients (21.6%) essentially because of transitoryransaminase increase (62.7%). However, statin with-rawal was not associated with postoperative AF devel-pment, AF recurrence, or persistent AF at dischargep � 0.840, p � 0.573, and p � 0.874, respectively; data nothown).There were also no statistical differences between

ig 1. The Kaplan-Meier cumulative estimates of postoperativetrial fibrillation (AF) free survival in patients with (---) preopera-ive statin therapy and in patients without (—) it (log-rank, p �

AF p Value No AF

0.90543 46.938.4 35.918.6 17.2

21.6 � 10.3 0.904 21.7 � 9.947.2 � 24.7 0.596 44.8 � 20.9

lation

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evelopment of AF and type, dose, or duration of preop-rative statin therapy (Table 4). Preoperative statin useas associated with less AF in the on-pump group (p �

.001) compared with the off-pump group (p � 0.060).Patients with preoperative statins had a shorter length

f hospital stay (LOS) compared with patients withouthem, although not significant (7.8 � 4.0 vs 8.4 � 4.7 days,

� 0.134). When considering the entire study popula-ion, no differences were observed in LOS in patientsffected by AF compared with patients without it (p �.575). Also, no differences were found in patients withreoperative statins affected by AF or not (7.7 � 4.4 vs.9 � 3.0 days, p � 0.816). There was no AF-specificifference in hospital mortality (p � 0.348) and in one-ear mortality (p � 0.300). The Kaplan-Meier actuarialstimates of occurrence of postoperative AF in bothroups showed a significantly better AF-free survival inhe statin group (Fig 1).

ultivariable Analysis (Stratified on the Propensitycore)e then evaluated the role of statins while stratifying on

he propensity score to adjust for the likelihood of receiv-ng the treatment, given the presenting characteristics.ndeed, preoperative treatment with statins was associ-ted with a 42% reduction in risk of AF development afterABG surgery (odds ratio [OR] 0.58, 95% confidence

nterval [CI] 0.37 to 0.91, p � 0.017). No different effect oftatins on AF was observed in the two age groups (�70nd �70 years) (interaction p � 0.711).In addition, at the analysis of the secondary endpoints,

atients with withdrawal from preoperative �-blockerherapy and patients with postoperative need of IABPoth appeared to be at higher risk of AF development,lthough statistical significance was not reached (OR.64, 95% CI 0.97 to 2.72, p � 0.062 and OR 2.29, 95% CI.65 to 8.06, p � 0.198, respectively).

omment

n our prospective observational study, preoperative sta-in therapy conferred a 42% reduction in risk of AF afterABG (OR 0.58, 95% CI 0.37 to 0.91). This result ac-

ounted for the likelihood of the patients being treatedith statins, given the presenting characteristics. Otherotential predictors of AF were postoperative withdrawalf �-blockers and postoperative IABP requirement. Onne hand, requirement for IABP in the perioperativeeriod can be assumed to mirror the status of myocardialysfunction with the need of postoperative inotropicrugs. Catecholamine enhancement triggered activitynd automaticity, both key points in the development ofostoperative AF [15, 17]. On the other hand, �-blockersntagonize the effects of catecholamines on the myocar-ium and have been studied extensively as prophylacticgents in this setting. Withdrawal from preoperative-blocker therapy has largely been postulated as causingostoperative AF [1, 2, 15, 18].The beneficial statin effect on AF has been described in

ifferent reports. Statins have been demonstrated protec- c

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ive against AF in patients with stable coronary disease19]. They also decreased the AF recurrence after externalardioversion and the incidences of death, unstable an-ina, and cardiac arrhythmias [20, 21]. Two recent studiesbserved a significant reduction in AF risk after cardiacurgery in patients with preoperative statin use [6, 7].imilar results with a threefold decrease in the odds ofF have been confirmed after noncardiac thoracic sur-ery [22]. The atorvastatin for reduction of myocardialysrhythmia after cardiac surgery study (ARMYDA-3) is

he only randomized, controlled trial of pretreatmentith statins in elective cardiac surgery patients [8]. In this

tudy, Patti and colleagues [8] randomized 200 patients toreoperative atorvastatin (40 mg/day) or placebo startingeven days before operation, observing a significantecrease in postoperative AF in the atorvastatin-treatedroup (35% vs 57%, p � 0.003), with a 61% reduction in AFisk at the multivariate level.

However, the protective mechanisms exerted by statinsemain unclear. The benefit of preoperative statins mayeflect their antiinflammatory effects and the role ofnflammation in the pathophysiology of postoperative AFas been widely demonstrated [1, 3, 4]. As a matter of

act, inflammatory markers as cytokine or circulatingdhesion molecules are attenuated in patients receivingtatins after cardiac operations [5, 23]. Antioxidant effect,irect antiarrhythmic effects by cell membrane ion chan-el stabilization or direct protection of the ischemicyocardium, and modulation of extracellular matrix are

lso reported properties [24, 25]. Moreover, the beneficialffects of statin therapy are not limited to patients withyslipidemia, but the incidence of adverse cardiovascularutcomes and the need for coronary revascularization areeduced even in patients with normal cholesterol levels [26].

The protective effects of statins on postoperative AF arealuable because this arrhythmia is the most frequentomplication after cardiac surgery and it is associatedith increased mortality and expenditure [1, 2]. In light of

he importance of postoperative AF to patient outcome,here has been a great deal of interest in preventing thisomplication pharmacologically. Amiodarone, �-blockergents, and sotalol have been found to reduce but notbolish this postoperative arrhythmia [18]. Several pa-ients still experience AF despite prophylactic therapy,nd a large number of the remaining patients are unnec-ssarily exposed to such drugs with potential adversevents [18]. Moreover, patients with deteriorated leftentricular function (LVF), COPD, and renal failure arerequently excluded from a prophylactic approach withart of the drugs; nevertheless, these patients are thenes most affected by AF, as demonstrated in severaltudies, and would benefit the most from a preventivereatment [18]. Statin therapy has a low cost, is a low riskreventive AF strategy, and all cardiac surgery patientsay benefit from such prophylactic regimen.In our study, however, no AF effects were observed in

OS in the entire population study nor in patients withreoperative statins. This discrepancy, compared with

he ARMYDA-3 study could be justified by the inclusion

riteria [8]. In our study, emergency operations were

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1163Ann Thorac Surg MARISCALCO ET AL2007;84:1158–65 STATINS AND POSTOPERATIVE ATRIAL FIBRILLATION

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ncluded. As a matter of fact, without considering unsta-le cases (23.5%), patients affected by postoperative AFxperienced a significantly longer hospital stay (7.9 � 2.7s 7.2 � 2.1 days, p � 0.025). Patients with statin therapylso revealed a shorter, but not significant LOS comparedith patients without it (7.3 � 2.2 vs 7.6 � 2.6 days).Our study was an observational investigation based on

rospectively collected data, and a selection bias mayave been presented because there was no homogenous

ndication for the use, type of lipid-lowering agents, anduration of preoperative statin therapy. Indication and

ype of statins were decided by the referring physicians.owever, our analysis accounted for this by assessing the

ole of statins while stratifying on the propensity score.oreover, the two groups of patients, statin and no statin

se, were comparable in preoperative and operativeharacteristics. The two groups were also reasonablyalanced in the absolute number of cases. Furthermore,ur aim was to explore only the statin effects on postop-rative AF, without modify at all preoperative drugegimens. Our peripheral cardiac surgery departmentoes not permit a preventive elective AF prophylactictrategy as reported by Patti and colleagues [8], with noossibilities to hospitalize patients several days before

he operation (seven days as in the ARMYDA-3 study;ur hospitalization before the operation was 2.4 � 1.2ays). But more importantly, emergent cases (23.5% ofur patients) are inevitably excluded from such therapy.he latest are most often older patients, suffering frometeriorated LVF and requiring inotropic drugs withrolonged hospital stay; both AF risk factors as demon-trated in several studies [1, 2, 14, 27]. Moreover, in alltudies regarding the statin effect on postoperative AF,atients with a preoperative history of AF were excluded

6, 8]. As largely demonstrated, these patients most oftenre at higher risk of developing postoperative AF [1, 2, 4].n our study we did not introduce any exclusion criterias we aimed to observe the highest possible proportion ofatients admitted for CABG. As a matter of fact, only 9%f the subjects were not included in the final analysis,eflecting the complete CABG patient population. On theontrary, in the ARMYDA study about 40% (123 of 323) ofospitalized patients were excluded [8]. Finally, we be-

ieve that observational studies like ours are still neededfter the publication of controlled clinical trials. Indeed,esults of controlled clinical trials may differ from resultsbtained in clinical practice. Generally, randomized trials

nvolve selected centers only and frequently includeounger, selected elective patients, with a lower inci-ence of comorbidities. Discrepancies between con-

rolled trials and clinical practice may be more pro-ounced when invasive procedures are involved. Anperator’s technical skill and careful patient follow-upay enhance the benefits of the procedure in the context

f the clinical trial. Therefore, confirmation of the trialesults by observational studies is eagerly needed. Thistudy, conducted in an unselected population, aimedt that purpose. A further limitation of this study is the

ack of the baseline assessment of inflammatory mark-

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rs, which have been associated with postoperative AF1, 3, 23].

In conclusion, preoperative statins seem to reduceostoperative AF development after CABG and consti-

ute a useful preventive pharmacologic approach in pa-ients undergoing elective revascularization.

eferences

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ppendix

dditional Analyzed Variables

reoperative (29): age, sex, BMI (body mass index), BSA (bodyurface area), preoperative cardiac rhythm, CCS angina classi-cation, angina presentation (stable or unstable), IABP (in-

raaortic balloon pump), previous AMI (acute myocardial infarc-ion), previous PCI (percutaneous coronary intervention), left

ain stem stenosis, right coronary artery stenosis; left ventric-lar function, left atrial antero-posterior diameter; hypertension,iabetes mellitus, hypercholesterolemia, BPCO (chronic ob-tructive pulmonary disease), peripheral vascular disease, cere-rovascular accident, renal failure, hemoglobin (g/dL), Euro-CORE; �-blocker agents; calcium-channel blockers, ACE

angiotensin-converting enzyme)-inhibitors; type of statins,ose of statins, duration of preoperative statin therapy.

Operative (11): CPB (cardiopulmonary bypass) use, cardiople-ia-route (antegrade, antegrade and retrograde), cardioplegia-ype (crystalloid or blood), cardioplegia-temperature (warm,old), CPB time, ACC (aortic cross-clamp) time, CPB tempera-ure, number of grafts, postoperative IABP, cardiac rhythm athe end operation, inotropic support.

Postoperative (19): time on ventilator, ICU (intensive carenit) time, mediastinal bleeding, fluid balance, MB peak; respi-atory failure, surgical revision for bleeding, perioperative AMI,emotransfusion; atrial fibrillation (AF) occurrence, AF occur-ence day, cardiac rhythm at discharge; LOS (length of hospitaltay), hospital mortality, one-year mortality; postoperative:-blocker agents, calcium-channel blockers, ACE-inhibitors,

tatins.

NVITED COMMENTARY

ariscalco and colleagues [1] report on the beneficialffect of preoperative administration of statin medica-ions in reducing atrial fibrillation (AF) after coronaryrtery bypass grafting (CABG). This effect was preservedn a multivariate analysis that considered other pertinentreoperative and intraoperative variables.The mechanisms responsible for postoperative AF

re not completely understood, but may include isch-mia, anatomic changes in the atrium, transient elec-rophysiologic and hemodynamic changes periopera-ively, and inflammation, among others. Theserrhythmias likely occur in patients at risk (eg, ana-omical substrate) because of a perioperative trigger.he motivation for the current study is the possibility

hat perioperative inflammation is related to the devel-pment of postoperative AF.In cardiac surgery, statins have recently received

ttention with the observation that pretreatment withtorvastatin reduced cytokine release and neutrophildhesion in patients undergoing CABG with cardio-ulmonary bypass. Two previous nonrandomizedtudies of preoperative statin therapy in patients un-

uration of postoperative AF were reduced. Most re-ently, a randomized trial of preoperatively used ator-astatin showed a significant reduction in postopera-ive AF in the treated group. Interestingly, the benefitf atorvastatin was not enjoyed by patients with lefttrial enlargement or those who were undergoingeart valve surgery.The current report involves a relatively small number

f patients and it is impossible to know if the study andontrol groups are similar except for the use of statins [1].onetheless, this study adds to the accumulating evi-ence that statins may be a useful strategy for helping torevent postoperative AF.We must keep in mind the entire body of evidence

elated to the prevention of postoperative AF [2]. Wenow that postoperative AF is related to preoperativeariables, including patient age and type of operation.e also know that mild rather than moderate degrees

f hypothermia may be protective. Accumulating evi-ence suggests that off-pump CABG may be associatedith a lower incidence of postoperative AF than con-

entional CABG. We also know that pharmacologic

nterventions such as beta-blockers or amiodarone

0003-4975/07/$32.00doi:10.1016/j.athoracsur.2007.06.102

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DOI: 10.1016/j.athoracsur.2007.05.021 2007;84:1158-1164 Ann Thorac Surg

Tozzi, Davide Vanoli, Bruno Vito Domenico and Andrea Sala Giovanni Mariscalco, Roberto Lorusso, Catherine Klersy, Sandro Ferrarese, Matteo

Atrial Fibrillation After Coronary SurgeryObservational Study on the Beneficial Effect of Preoperative Statins in Reducing

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