role of statins in the coronary bypass patients

ROLE OF STATINS IN THE CORONARY BYPASS PATIENTS Thesis Submitted in Partial Fulfillment of the Requirement for M.D. Degree in Cardiothoracic Surgery

By EHAB FAWZY SALIM M.B.B.ch, M.S.

Supervisors

EZZELDIN A. MOSTAFA

AHMED M. ALY

MD, PhD

MD, PhD

Professor of Thoracic and Cardiovascular Surgery Ain Shams University

Professor of Thoracic and Cardiovascular Surgery Benha University

GAMAL SAMY

AHMED ABD ELAZIZ

MD, PhD

MD, PhD

Professor of Thoracic and Cardiovascular Surgery Ain Shams University

Associate Professor of Thoracic and Cardiovascular Surgery Ain Shams University

Ain Shams University 2009

‫دور ﻋﻘﺎر اﻷﺳﺗﺎﺗﻳن ﺑﻌد ﻋﻣﻠﻳﺔ زرع اﻟﺷراﻳﻳن اﻟﺗﺎﺟﻳﺔ‬

‫دراسة مقدمة‬ ‫للحصول على درجة الدكتوراه فى جراحة القلب والصدر‬

‫مقدمة من‬ ‫إيھــاب فــوزى سالــم‬

‫تحت إشراف‬ ‫األستاذ الدكتور‬ ‫أحمـــد محمـــود علــــى‬

‫األستاذ الدكتور‬ ‫عز الدين عبد الرحمن مصطفى‬

‫أﺳﺗﺎذ ﺟراﺣﺔ اﻟﻘﻠب واﻟﺻدر‬

‫أﺳﺗﺎذ ﺟراﺣﺔ اﻟﻘﻠب واﻟﺻدر‬

‫ﺟﺎﻣﻌﺔ ﺑﻧﻬﺎ‬

‫ﺟﺎﻣﻌﺔ ﻋﻳن ﺷﻣس‬

‫األستاذ الدكتور‬ ‫جمـــــال ســـامى‬

‫الدكتــــور‬ ‫أحمـــد عبــد العـــزيز‬

‫أﺳﺗﺎذ ﺟراﺣﺔ اﻟﻘﻠب واﻟﺻدر‬

‫أﺳﺗﺎذ ﻣﺳﺎﻋد ﺟراﺣﺔ اﻟﻘﻠب واﻟﺻدر‬

‫ﺟﺎﻣﻌﺔ ﻋﻳن ﺷﻣس‬

‫ﺟﺎﻣﻌﺔ ﻋﻳن ﺷﻣس‬

‫جامعـــة عيـــن شمــــس‬

‫‪2009‬‬

ACKNOWLEDGEMENT First and foremost thanks are due to GOD the beneficent and merciful. I am greatly honored to express my gratitude to my Prof. Dr EZZELDIN A. MOSTAFA, Prof. of Cardiothoracic Surgery, Ain Shams Faculty of medicine, Ain Shams University, who sacrificed great deal of his valuable time in meticulous revising this study and for whom no words of praise are sufficient. It was a great honor to work under his supervision. I would like to express my deepest gratitude to Prof. AHMED MAHMOUD ALI, Prof. of Cardiothoracic surgery department, Benha Faculty of medicine, Benha University, to whom I'm very fortunate to be one of his students, for his support, valuable comment and advice throughout this work. He was generous with time and effort. I do feel greatly indebted to Prof. GAMAL SAMY, Prof. of Cardiothoracic Surgery, Ain Shams Faculty of medicine, Ain Shams University, for his kind and indispensable guidance, patience with me and who has been of invaluable assistance in making this work outstanding from the point of view of accuracy, style, content, and expression. I am also grateful to Dr. AHMED ABD ELAZIZ, Assistant Prof, of cardiothoracic surgery, Ain Shams Faculty of medicine, Ain Shams University, for his great care and patience, tremendous efforts and advice throughout this work. Finally, I wish to thank my family and my colleagues and members of Cardiothoracic Surgery department for their encouragement and help. EHAB FAWZY SALIM, 2009

TABLE OF CONTENT Title Abstract Introduction Aim of the study The coronary artery disease The mechanisms of action of statins Indications for coronary bypass surgery Preoperative evaluation Postoperative role of statins Patients and methods Results Discussion Summary and Conclusion Reference Arabic summary

-i-

Page N0. vi 1 2 3 8 18 22 35 45 51 68 85 88 102

LIST OF TABLES TABLE No. TABLE 1 TABLE 2 TABLE 3 TABLE 4 TABLE 5 TABLE 6 TABLE 7 TABLE 8 TABLE 9 TABLE 10 TABLE 11 TABLE 12 TABLE 13 TABLE 14 TABLE 15 TABLE16

TITLE Statin Agents; Dosing, Side-Effects, Interactions and Lipid-Lowering Effects AHA/ACC guidelines for CABG Canadian Cardiovascular Society angina classification (CCS) Preoperative patients’ profiles and preoperative data of the two groups. Preoperative laboratory results of the two groups. Preoperative lipid profile of the two groups. Operative data of the two groups. Comparison of outcome of group I and II. Postoperative renal functions in group I and II. Postoperative follow-up of liver functions. Lipid profile follow-up in the 1st , 3rd and 6th months postoperatively. Comparison of echocardiography of group I and II. Comparison of perfusion imaging scan of group I and II. Incidence of early cardiovascular outcome after the first month postoperatively. Incidence of cardiovascular outcome within the first 6 month postoperatively. Studies investigating the effect of statin therapy on patients undergoing coronary artery bypass grafting.

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PAGE 9 18 22 52 54 55 57 59 59 60 61 62

66 67 76

LIST OF FIGURES FIGURE No. FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5

FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17

TITLE PAGE Normal coronary artery histology. 3 Atherosclerosis of native coronary arteries & the 4 coronary arteries of transplanted hearts. Theory of atherogenesis and atherosclerosis (the 6 response-to-injury hypothesis). Dual mechanism of action of statins. 8 Comparison of onset, peak and duration of 29 elevation of serum levels of cardiac markers associated with acute myocardial infarction. Preoperative patients’ profiles and preoperative 53 risk factors of the two groups. Preoperative creatinine and bilirubin of the two 54 groups. Preoperative AST and ALT of the two groups. 54 Preoperative patients’ lipid profiles of the two 55 groups. 57 Operative data of the two groups. Postoperative Data. 59 Postoperative follow-up of liver functions. 60 Postoperative follow-up of lipid profile at the end 61 of the 6th month postoperatively. Comparisons of echocardiography of group I 63 and II after 1 and 6 months postoperatively. Comparison of perfusion imaging scan of group I 64 and II. Incidence of early cardiovascular outcome after 66 the first month postoperatively. Incidence of cardiovascular outcome within the 67 first 6 month postoperatively.

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LIST OF ABBREVIATION: ACC ADP AF AHA AMI ATP BMI CABG CAD CCS CK CPB ECG EF EPC FEV1 FS HDL HMG IABP IHD IL-6 IL-8 INR LAD LDL LITA LVEDP LVF MCA MCP-1 MI

American College of Cardiology. Adenosine diphosphate. Atrial fibrillation. American Heart Association. Acute myocardial infarction. Adenosine triphosphate. Body mass index. Coronary artery bypass grafting. Coronary artery disease. Canadian Cardiovascular Society. Creatine kinase. Cardiopulmonary bypass. Electrocardiography. Ejection fraction. Endothelial progenitor cells. forced expiratory volume in 1st second. Fraction shortening. High-density lipoproteins. 3-hydroxy-3-methylglutaryl. Intraaortic balloon pump. Ischemic heart disease. Interleukin-6. Interleukin-8. International normalized ratio. Left anterior descending artery. Low-density lipoproteins. Left internal thoracic artery. left ventricular end diastolic pressure. Left ventricular function. Middle cerebral artery. Monocyte chemoattractant protein- 1. Myocardial infarction.

- iv -

MMPs MSCT MVA NCEP NYHA NO PA1-I PDGF PET PMLs PTCA PTT SMC SPSS SVT TC TF TG TSP-1 TxA2 VSD

Matrix metalloproteinases. Multislice computed tomography. Mevalonic acid. National Cholesterol Education Program .

New York Heart Association. Nitric oxide. Plasminogen activator inhibitor 1. Platelet-derived growth factor. Positron emission tomography. polymorphonuclear leukocytes. Percutaneous transluminal coronary angioplasty. Partial thromboplastin time. Smooth muscle cell. Statistical package for social science. Supraventricular tachycardia. Total cholesterol. Tissue factor. Triglycerides. Thrombospondin-1. Thromboxane A2 . Ventricular septal defects.

-v-

Abstract

Role of statins in the coronary bypass patients Ehab Fawzy Salim, M.B.B.ch, M.S. Back ground and objectives: An increasing evidence suggests that statin therapy is beneficial to patients undergoing CABG. In this study, statin therapy will be shown to minimize adverse cardiac events, and decrease the need for repeat revascularization after CABG. Methods: 60 patients have (CABG) enrolled in this non-randomized prospective study divided into 2 groups: Group I: 25 males and 5 females with mean age (54.4 ± 9.04) receiving statin. Goal LDL < 100 mg/dl. Group II: 26 males and 4 females with mean age (56.5 ± 6.4) not receiving statin. Preoperative risk factors, operative data and postoperative details(including ICU time, hospital stay, post operative complications and complete laboratory profile, need for inotropic support or intra aortic balloon pump) were recorded. Results There was significant difference between the groups regarding occurrence of unstable angina(6.6% in group I versus 26.6% in group II, p value=0.038), value=0.017),AF(6.6% in group I versus 26.6% in group II, p value=0.038),total hospital stay(8.70±2.5 in group I versus 13.7±9.8 in group II, p adverse outcome(10% in group I versus 63.6% in group II, p value=0.012)and lipid profile (p value 200 mg/dl before CABG.

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Patients and methods

6- Contraindications to statin therapy:  Active liver disease.  Unexplained persistent elevation of serum alanine transaminase (i.e. more than three times the upper limit of normal).  History of hypersensitivity to statins. 7- Significant drug-drug interaction (i.e. concomitant use of cyclosporine, erythromycin or ketoconazole). 8- Patients over 70 years old.

Study protocol ■ PREOPERATIVE EVALUATION 1-HISTORY AND RISK FACTORS: All patients in the 2 groups had full clinical history and risk factors including: age, sex, smoking, angina (CCS), dyspnea (NYHA), hypertension, hypercholesterolemia, and previous MI (>30 days), previous stroke, and previous stenting. Preoperative evaluation, operative details, postoperative course and outcome are recorded. 2-LABORATORY INVESTIGATIONS: All patients were submitted for routine tests including complete blood count, liver function tests, kidney function tests, coagulation profile, lipid profile, serum proteins and blood sugar levels. 3-ECG: Routine ECG was done preoperatively. 4-RADIOLOGICAL INVESTIGATIONS: CHEST X-RAY: Routine PA chest x-ray was done preoperatively. ECHOCARDIOGRAPHY: This was done preoperatively for evaluating the systolic function of the left ventricle with M-mood, measuring end-systolic, end-diastolic diameters and the ejection fraction. PERFUSION IMAGING SCAN: Perfusion imaging scan with thallium-201 or a technetium-99m tracer (if available).

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Patients and methods CORONARY ANGIOGRAPHY: Cardiac catheterization was done for all patients preoperatively. ■ OPERATIVE DATA The anesthetic management, myocardial protection, perfusion data surgical techniques, intraoperative events were recorded. Patients continue on the same drugs that they usually use until the morning of the surgery except anti-platelets, which are stopped for 7 days preoperative. In operating room, a peripheral venous line was inserted. Radial artery of the dominant arm is used for invasive blood pressure monitoring. Patients monitored with five leads electrocardiograph (ECG) and pulse oximetry. Induction of anesthesia: All patients pre-oxygenated with 100% oxygen for three minutes using facemask. Then, anesthesia started using 10-20 µg/kg fentanyl, and 12 mg/kg thiopental. Muscle relaxation was achieved by using pancuronium in dose 0.1-0.15 mg/kg. Patients were ventilated manually for another two minutes until complete relaxation, then oral endotracheal tube was inserted, the cuff was inflated, and the tube was secured. Patients were then connected to mechanical ventilation. Urinary catheter and central venous line are then inserted. Maintenance of anesthesia: Patients were mechanically ventilated using with 100 % oxygen, and tidal volume and respiratory rate were adjusted to keep the arterial pressure of CO2 (Pa CO2 between 30-40 mmHg). Anesthesia was maintained by giving the patients incremental dose of Fentanyl and/or isoflorane (0.5-1.0 %) inhalation when the increase in blood pressure exceeds the pre-induction values by more than 20% SURGICAL TECHNIQUE: GENERAL PRINCIPLES: Surgical access to the heart was through median sternotomy in all cases. All incisions and closure techniques were the same for both groups. Fine monofilament polypropylene suture (8-0 or 7-0 surgipro) was used for - 47 -

Patients and methods

all distal anastomoses. Proximal anastomoses were performed with Fine monofilament polypropylene suture (6-0 surgipro) for venous anastomoses and (6-0 or 7-0 surgipro) suture for arterial anastomoses to the aorta. CABG WITH CARDIOPULMONARY BYPASS (CPB) TECHNIQUE: All patients were done with cardiopulmonary bypass (CPB) technique.This was accomplished with aortic cannulation, and two stage venous cannula. Membrane Oxygenator and Heart-Lung machine were used. Preparation for cardiopulmonary bypass: Systemic heparinization achieved by administration of intravenous heparin sulphate (300 iu/ kg). Safe level of heparinization was certified by an activated clotting time (Haemochrone) to be more than 400 seconds before aortic and venous cannulae were inserted. Cardiopulmonary bypass is conducted using membrane oxygenator and a non-pulsatile flow according to body surface area. The circuit was primed with 1500 ml Ringer lactate solution and 150 ml Mannitol 20 % to achieve moderate hemodilution (haemotocrit 0.20 to 0.25). We may use blood to achieve this haemotocrit value. Myocardial protection consisted of repeated infusions of Antegrade Cold blood cardioplegia solution every 25-30 minutes (4° C; potassium chloride=28mEq/L) supplemented with mild hypothermia (35°C) and topical cold saline lavage at 4°C. After successful separation from cardiopulmonary bypass, reversal of heparin action is achieved by giving protamine sulphate at a ratio 1 mg for each 100 IU Heparin. After obtaining medical and surgical homeostasis,drains are inserted, the sternum is closed and patients are transported intubated and manually ventilated to the intensive care unit (ICU); being monitored during transportation for ECG, pulse oximetry and invasive arterial blood pressure. After arrival to ICU, patients were mechanically ventilated on 7-10 ml /kg tidal volume, 80% oxygen, respiratory rate 11-14 / minute. Patients were monitored by ECG, pulse oximetry, invasive arterial blood pressure, rectal temperature, blood gases, and serum electrolytes.

- 48 -

Patients and methods ■ POSTOPERATIVE DATA THE 1CU: ICU events were recorded including the need for support, usage of intraaortic balloon pump (IABP), the need for transfusion, ICU stay in hours and hospital stay in days. Criteria for weaning and extubation include:  Inspiratory force of 20 cm H2O or more.  Respiratory rate less than 30 breath / minute.  Oxygen saturation more than 90%.  PH 7.35 to 7.45.  PaCO2 less than 50 mmHg. Criteria for ICU discharge Before transfer from ICU, patients had to be extubated, and had stable vital signs without any inotropic support; and the drains are removed. Criteria for hospital discharge  Include normal sinus rhythm or the preoperative controlled AF, no S-T segment depression or elevation.  Normothermia.  Oxygen saturation greater than 90% while breathing room air. POSTOPERATIVE COMPLICATIONS: Any postoperative complications were included as reexploration, perioperative myocardial infarction, unstable angina, acute renal failure, cerebral stroke, arrhythmia, superficial and deep infection and mortality. 1-LABORATORY INVESTIGATIONS: All patients were submitted postoperatively for routine laboratory tests including complete blood count, liver function tests, kidney function tests, coagulation profile, serum proteins and blood sugar levels. Lipid profile was followed-up in the 1st , 3rd and 6th months postoperatively. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines were utilized as the standard of care (126). - 49 -

Patients and methods Liver function tests were also followed-up in the 1st , 3rd and 6th months postoperatively. 2-ECG: Routine ECG was done postoperatively at the 1CU, morning following surgery, at discharge and whenever indicated and compared with the preoperative one. 3-RADIOLOGICAL INVESTIGATIONS: CHEST X-RAY: Routine PA chest x-ray was done postoperatively after admission to ICU, daily in the ICU, and at discharge from hospital. ECHOCARDIOGRAPHY: This is done for evaluating the systolic function of the left ventricle with M-mood, measuring end-systolic, end-diastolic diameters and the ejection fraction. Each patient had 2-serial postoperative echocardiograms, done at one and six months after the operation date respectively and compared with the preoperative one. PERFUSION IMAGING SCAN: Perfusion imaging scan with thallium-201 or a technetium-99m month tracer was done in some cases in both groups at the 6th postoperatively and data was compared with the preoperative perfusion imaging scan.

■ STATISTICS The data were collected and analyzed using the statistics analysis program SPSS 15. The data presented are the actual number of occurrences in a group and the mean plus or minus the standard deviations. We use the Chi square analysis and Fisher exact two-sided test to compare occurrence between both groups. ANOVA test was used to compare measured data between both groups. Data were considered significant if P value is less than 0.05

- 50 -

PATIENTS AND METHODS This is a prospective study designed to study the effect of lipid lowering therapy on the coronary circulation and documenting the particular improvement of the clinical outcomes in coronary bypass patients through improvement of myocardial perfusion and therefore minimizing recurrent ischaemic events in addition to decreasing the need for repeating revascularization procedures in patients who have undergone coronary artery bypass grafting. The study comprised, 60 patients in Ain Shams University Hospitals and Nasser Institute Hospital starting on July 2007 till January 2009.

■ STATISTICS The data were collected and analyzed using the statistics analysis program SPSS 15. The data presented are the actual number of occurrences in a group and the mean plus or minus the standard deviations. We use the Chi square analysis and Fisher exact two-sided test to compare occurrence between both groups. ANOVA test was used to compare measured data between both groups. Data were considered significant if P value is less than 0.05

Results

Results During the study, 60 patients were eligible for the study; all of them were enrolled in the study and completed the protocol, thirty patients in each group. The data of both groups were compared and results were obtained by using statistical analysis program SPSS 15. Patients’ profiles and preoperative data: There was no significant statistical difference between the two groups in most of the risk factors. Table (4) and Figure (6) show the comparison between the two groups regarding the patients’ profile and risk factors. AGE: Group I had a minimum age of 39 years and a maximum age of 68 years with a mean of 54.4 ± 9.04 years, while Group II had a minimum age of 43 years and a maximum age of 68 years with mean of 56.5 ± 6.4 years(P value =0.30). GENDER: There were 5 (16.6%) females in Group I, while Group II had 4(13.3%) females (P value =0.72). ANGINA CCS CLASS III OR IV: Group I had 10(33%) patients with CCS class III or IV, while Group II had 6 (20%) patients with CCS class III or IV (P value =0.17). NYHA FUNCTIONAL CLASS I I I OR IV: Group I had 6(20%) of patients with NYHA functional class III or IV while Group II had 6(20%) patients with NYHA functional class III or IV (P value =0.12). HYPERTENSION: Group I had 20 (66.6%) hypertensive patients, while Group II had 21(70%) patients (P value =0.78).

- 51 -

Results PREVIOUS MYOCARDIAL INFARCTION: Group I had 3(10%) patients with previous MI, while Group II had 4 (13.3%) patients with previous MI (P value =0.69). PREVIOUS CORONARY STENTING: Group I had 1(3.3%) of patients with previous coronary stenting, while Group II had 5(16.6 %) patients with previous coronary stenting (P value =0.08). SMOKING: The incidence of smoking was 20(66.6%) patients and 16 (53.3%) patients for Groups I and II respectively (P value =0.30). ●There was no AF preoperatively. ●No patients need intra-aortic balloon pump (IABP) preoperatively. Table (4): Preoperative patients’ profiles and preoperative data of the two groups. Groups Group I Group II N = 30 N = 30 P value Significance Variables Mean + SD Mean + SD (or N + %) (or N + %) 54.4 ± 9.04 56.5 ± 6.4 AGE 0.30 NS 25(83.3%) 26(86.7%) MALE(percent) 0.70 NS 5 (16.6%) 4(13.3%) FEMALE(percent) 0.72 NS 20(66.6%) 16 (53.3%) SMOKERS 0.30 NS HYPERTENSION (percent) (on regular treatment) EF Old MI (percent) STENT NYHA grade III,IV CCS class III,IV

20(66.6%)

21(70%)

54.7 ± 6.4% 3(10%) 1(3.3%) 6(20%) 10(33.3%)

55.3±5.4% 4(13.3%) 5(16.6%) 6(20%) 6(20%)

0.78 0.72 0.69 0.08 0.12 0.17

NS NS NS NS NS NS

NS: Non-significant (P >0.05). EF=Ejection Fraction, MI=Myocardial Infarction, NYHA=New York Heart Association, CCS=Canadian Cardiovascular Society.

- 52 -

Results

80 70 60 50 40 30

group 1

20 10

group 2

IV

IV III

&

& CS

III C

N

YH

A

St en

t

M I

O ld

EF

m Sm ale H yp oke r er te s nt io n

Fe

A

ge

0

Figure (6): Preoperative patients’ profiles and preoperative risk factors of the two groups. LABORATORY FINDINGS: Most of the preoperative laboratory findings showed no significant statistical difference (P value >0.05) between the two groups. Table (5) and table (6) show the comparison between the two groups regarding the preoperative laboratory results. KIDNEY FUNCTION TESTS: The Creatinine levels were 1.04 ± 0.22 mg% and 1.02 ± 0.29 mg% in Groups I and II respectively (P value =0.73). LIVER FUNCTION TESTS: The AST in Group I were 33.33 ± 8.10 u/l, while in Group II were 33.30 ± 7.01 u/l respectively (P value =0.98). The ALT in Group I 30.26 ± 9.30 u/l, while in Group II were 29.73 ± 9.12 u/l respectively (P value =0.82). The bilirubin levels were 0.58 ± 0.18 mg% and 0.64 ± 0.29 mg% in Groups I and II respectively (P value =0.33).

- 53 -

Results

1.2

34

1

33

0.8

32 IU /L

m g /d l

Table (5): Preoperative laboratory results of the two groups. Groups Group I Group II N = 30 N = 30 P value Significance Variables Mean + SD Mean + SD CREATININE 1.04 ± 0.22 1.02 ± 0.29 0.73 NS BILIRUBIN 0.58 ± 0.18 0.64 ± 0.29 0.33 NS AST 33.33 ± 8.10 33.30 ± 7.01 0.98 NS ALT 30.26 ± 9.30 29.73 ± 9.12 0.82 NS NS: Non-significant (P >0.05). ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase.

0.6

31 30

0.4

29

0.2

28

0

27

c reatinine

bilirubin

Figure(7): Preoperative creatinine and bilirubin

AS T

g roup 1 g roup 2

AL T

g roup 1 g roup 2

Figure(8): Preoperative AST and ALT AST = Aspartate Aminotransferase, ALT = Alanine Aminotransferase.

LIPID PROFILE: There was a significant statistical difference between the two groups regarding total cholesterol which was 196.1 ± 36.9 in Group I, while it was 214.2 ± 24.8 in Group II (P value =0.029). There was a significant statistical difference between the two

- 54 -

Results groups regarding LDL which was 127.7 ± 35.2 in Group I, while it was 150.6 ± 26.3 in Group II (P value =0.006). There was a significant statistical difference between the two groups regarding HDL which was 36.30 ± 6.01 in Group I, while it was 33.60 ± 4.8 in Group II (P value =0.034). There was no significant statistical difference between the two groups regarding TG which was 157.3 ± 39.1 in Group I, while it was 149.5 ± 27.2 in Group II (P value =0.37). Table(6): Preoperative lipid profile of the two groups. Groups Variables TOTAL CHOLESTEROL LDL HDL TG

Group I N = 30 Mean + SD

Group II N = 30 Mean + SD

196.1 ± 36.9

214.2 ± 24.8 0.029

127.7 ± 35.2 150.6 ± 26.3 36.30 ± 6.01 33.60 ± 4.8 157.3 ± 39.1 149.5 ± 27.2

LDL: low density lipoproteins,

P value

0.006 0.034 0.37

Significance S S S NS

HDL: high density lipoproteins,

TG: triglycerides.

250

mg /dl

200 150 g roup 1

100

g roup 2

50 0 T otal c holes terol 

L DL

HDL

TG

Figure (9): Preoperative patients’ lipid profiles of the two groups.

- 55 -

Results ECG: There was no significant difference in the ECG changes for both groups. RADIOLOGICAL FINDINGS: There was no statistical significant difference between the two groups in all findings (P value >0.05) ECHOCARDIOGRAPHY: There was no statistical significant difference between the two groups regarding the mean preoperative ejection fraction which was 54.7 ± 6.4% and 55.3±5.4% for Groups I and II respectively (P value =0.72). CARDIAC CATHETER: Group I had a mean of 2.73 ± 0.94 diseased vessels, while Group II had a mean of 2.60± 0.89 diseased vessels, with insignificant statistical difference (P value =0.58).

OPERATIVE RESULTS Mammary artery graft was used in all patients in both groups. It was used to the left anterior descending artery in all patients and the saphenous vein was used to complete myocardial revascularization of other coronary branches. Table (7) and Figure (10) show the comparison between the two groups regarding the operative data. COMPLETE REVASCULARUZATION: There was no significant difference regarding the percent of complete revascularization (Group I 96.7%, Group II 93.3%, and P value =0.56). (Complete revascularization means that vessels planed preoperatively for revascularization are all done intra operative). ENDARTERECTOMY: One patient in Group II needed endarterectomy for LAD. CPB AND CROSS CLAMP TIME: In Group I, CPB time was 86.3±30.9 minutes while in Group II

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Results CPB time was 85.8±27.7 minutes, with insignificant statistical difference (P value =0.94). In Group I, cross-clamp time was 63.8±26.3 while in Group II, cross-clamp time was 59.7 ± 22.5 minutes with insignificant statistical difference (P value =0.52). ● ●

No patients need IABP intraoperatively. All patients resume intraoperatively.

sinus

rhythm

Table (7): Operative data of the two groups. Group I Group II Groups N = 30 N = 30 Mean + SD Mean + SD Variables (or N + %) (or N + %) CPB TIME 86.3±30.9 85.8±27.7 CROSS-CLAMP TIME 63.8±26.3 59.7 ± 22.5 COMPLETE REVASCULARIZATION

96.7%

93.3%

spontaneously

P value

Significance

0.94 0.52

NS NS

0.56

NS

NS: Non-significant (p > 0.05).

120 100 80 60

g roup 1 g roup 2

40 20 0 C P B  time(min)

C ros s  c lamp time(min)

C omplete revas c ulariz ation(% )

Figure (10): Operative data of the two groups.

- 57 -

Results

POSTOPERATIVE RESULTS All patients were admitted to the 1CU. All patients received oral aspirin 150 mg postoperatively commenced within the first 24 hours after the operation and continued indefinite. I-THE ICU RESULTS: INOTROPIC SUPPORT: There was no significant difference between both groups regarding inotropic support which was used in 20 (66.6%) patients in Group I and in 25 (83.3%) patients in Group II (P value =0.08). IABP: There was no significant difference between both groups regarding IABP which was used in 1 (3.3%) patient in Group I and in 3 (10%) patients in Group II (P value =0.30). BLOOD PRODUCT TRANSFUSION: There was no significant difference regarding the blood product transfusion which was used in 8 (26.6%) patients in Group I and in 7 (23.3%) patients in Group II (P value =0.77). ICU AND HOSPITAL STAYS: There was no significant difference between both groups regarding ICU stay (Group I : 1.46±0.97 days versus Group II : 1.16 ±0.37 days P value = 0.12). There was significant difference between both groups regarding the hospital stay (Group I : 8.70±2.5 days versus Group II : 13.7±9.8 days P value = 0.017).

- 58 -

Results Table (8): Comparison of outcome of group I and II. Groups Variables INOTROPES IABP BLOOD TRANSFUSION ICU STAY HOSPITAL STAY

Group I N = 30 Mean + SD (or N + %) 20 (66.6%) 1 (3.3%) 8 (26.6%) 1.46±.97 8.70±2.5 S: significant.

90 80 70 60 50 % 40 30 20 10 0

Group II N = 30 Mean + SD (or N + %) 25 (83.3%) 3 (10%) 7 (23.3%) 1.16 ± .37 13.7±9.8

P value

Significance

0.08 0.30 0.77 0.12 0.017

NS NS NS NS S

days

16 14 12 10 8 6 4 2 0

Ino trop e

IC U  s tay

IAB P g roup 1 g roup 2

H o s pital s tay g roup 1 g roup 2

Figure (11): Postoperative Data. II-LABORATORY RESULTS: There is no significant difference regarding the postoperative renal functions in both groups (table 9). Table (9): Postoperative renal functions in group I and II: Groups

Group I N = 30

Group II N = 30

Variables

Mean + SD

Mean + SD

CREATININE UREA

1.23 ± 0.25 1.26± 0.31 25.17 ± 10.42 27.13 ± 11.71 NS: Non-significant, (P > 0.05).

- 59 -

P value

Significance

0.40 0.22

NS NS

Results There is no significant difference regarding the postoperative liver functions in both groups. Liver functions was followed-up in the 1st , 3rd and 6th months postoperatively (table 10 and figure 12). Table (10): Postoperative follow-up of liver functions. Postopera- Groups tive date (months) Variables 1st 1st 3rd 3rd 6th 6th

AST ALT AST ALT AST ALT

Group I N = 30

Group II N = 30

Mean + SD Mean + SD 47.23 ± 11.64 44.20 ± 14.53 47.53 ±10.15 45.60 ± 12.95 50.00 ± 9.08 47.50 ± 11.66

44.03 ±15.04 40.93 ± 10.60 45.31 ± 12.46 42.06± 9.36 46.51 ± 9.73 43.63 ± 8.10

P value

Significance

0.36 0.32 0.39 0.24 0.12 0.09

NS NS NS NS NS NS

NS: Non-significant, (P > 0.05). ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase.

60 50 40 IU /L

g roup 1

30

g roup 2

20 10 0 AS T  1

AL T  1

AS T  3

AL T  3

AS T  6

AL T  6

Figure (12): Postoperative follow-up of liver functions. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase. 1=1stmonth, 3=3rd month, 6= 6th month. There was a significant difference regarding the postoperative lipid profile in both groups. Lipid profile was followed-up in the 1st , 3rd and

- 60 -

Results 6th months postoperatively (table 11). Table (11) : Lipid profile follow-up in the 1st , 3rd and 6th months postoperatively. Postopera- Groups tive date (months) Variables

Group I N = 30

Group II N = 30

Mean + SD Mean + SD

P value

Significance

178.9 ± 22.12 221.0 ±19.78