A COMPARATIVE SURVEY OF SURVIVAL OF CARDIAC PATIENTS WITH 3VD AND SEVER VEN- TRICULAR HEART FAILURE UNDER CABG AND MFU TREATMENTS USING COX REGRESSION

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1 Acta Medica Mediterranea, 2016, 32: 2037 A COMPARATIVE SURVEY OF SURVIVAL OF CARDIAC PATIENTS WITH 3VD AND SEVER VEN- TRICULAR HEART FAILURE UNDER CABG AND MFU TREATMENTS USING COX REGRESSION KHOSRO FARHADI *, HAMIDREZA SHETABI *, JAVAD AMINI SAMAN *, HASSANALI KARIMPOUR *, SOUDABEH ESKANDARI **, SHAHROKH CHEGHAZARDI *** * PhD of anesthesia, Anesthesia Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran - ** MSc of biostatistics, Biostatistics and Epidemiology Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran - *** PhD of cardiovascular diseases, Cardiovascular Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran Abstract Introduction: Cardiac diseases are of the most prevalent causes of death in the developed countries and the whole world as well. According to the forecasts by the World Health Organization, the diseases will be the main cause of death in the world by The most common surgery operation in coronary artery disease is coronary artery bypass grafting (CABG) and medical follow-up (MFU). Survival of 3VD and severe ventricular heart failure patients in two groups of CABG and MFU was compared. Methodology: A retrospective cohort study on 269 patients between 2009 and 2011 was carried out in Imam Ali Medical Educational Center. The 3VD patients underwent coronary artery angiography and had EF<30% so that CABG was prescribed form them. Male and female constituted 78% and 22% of the study group and average age of the participants was 61.40±9.07. The patients were categorized in two groups of CABG and MFU. Follow up was carried out until November 2014 to record any case of death. Kaplan-Meier survival analysis and Cox regression were used for data analysis. All the analyses were performed in STATA (12) with sig.=0.05. Findings: The results showed that despite their clear effects on development of coronary artery problems, the demographic information had no significant effect on clinical outcome of the patients. One month, six months, one year, and three years survival of CABG patients was 96.7%, 95.3%, 94.7%, and 89.8% respectively and these figures for the pharmaceutical medication patients were 97%, 92.5%, 86.3%, and 83.4% respectively. In addition, survival term in MFU and CABG patients was ± 1.64 and ± 1.23 months respectively. The most important factor effective on survival of patients according to Cox regression model was left ventricular EF. Conclusion: The findings indicated that survival rate was significantly related to the type of medical intervention. That is, survival rate of CABG group was higher than that of MFU group. Risk rate of CABG and MFU patients increased considerably after 30 and 20 months respectively. Keywords: survival analysis, cardiac patients, CABG, MFUtion, emotion regulation difficulties. Received April 30, 2016; Accepted July 02, 2016 Introduction Cardiovascular diseases are of the main cause of death in the world (1, 2). Fifty percent of deaths in the developed countries (5 million out of 12 million deaths) is due to cardiovascular diseases (3). However, these studies can be questioned from different viewpoints because at the time of doing them, there were few medical treatments and secondary prevention methods available. Still, given the rate of decrease of cardiovascular and cerebral problems over one year, CABG has become the standard treatment for coronary arteries diseases such as 3VD and CAD left main (4). Studies conducted in this field have mainly focused on detecting risk factors for these patients.

2 2038 Khosro Farhadi, Hamidreza Shetabi et Al The presents study, however, is aimed at forecasting survival of CABG and MFU patients based on survival analysis using Cox model. Majority of the researchers in medical fields tend to use semiparametrical models such Cox s models as they are featured with fewer presumptions comparing with parametrical models (5). Cox model assumes that the hypothesis of relevance of risks is supported for all the independent variables in the final model; that is, risk ratio remains a constant. If the hypothesis is supported, interpretation of the obtained model is easier comparing with parametrical model. By adding other variables to the model, the Cox model used in this study is featured with specific features to spot significant variables in addition to estimating risk function (6). Taking into account that there is no comprehensive study on survival rate of 3VD patients with EF < 35% with MFU and CABG treatments, the present study is aimed at estimating survival rate at different time rages and survey the factors effective on survival of the patients in Kermanshah Province, Iran. Methodology cohort study on medical records of 296 patients who referred to Imam Ali Medical and Educational Center (affiliated with Kermanshah University of Medical Science and Health Services) due to pain in the chest, cardiac infraction, and dyspnea. Coronary artery angiograph and echocardiography were performed on them (LVGF 30%) and the examinations confirmed 3VD case. Afterward, some patients received CABG intervention and some MFU (refusal to do surgery). The subjects were selected through census sampling. Equal number of CABG and MFU patients were selected and follow up was carried out until November Afterward, the patients were rechecked and examined based on a special questionnaire. Any case of hospitalization, arrhythmia, EF before and after angiography, death, and the like were recorded after the intervention and the more information was collected from medical file of the participants. Ethical considerations were taken into account and approval of ethics committee was secured in advance. Then, the patients who had been a candidate for MFU due to their coronary artery condition and the patients with valvular heart diseases were removed from the participants list so that 334 remained in the list. Because the communication ways were limited to medical file and telephone number, 39 patients without a phone number were removed. The study was conducted with 296 participants and the required data was collected from medical files and by telephone contact or personal visits. Inclusion criteria were not included a specific age range or similar limitations so that all 3VD patients with EF 30%, without valvular heart problems who received CABG were candidate participants. Demographic information (e.g. age, gender, height, and weight), risk factors (diabetes, blood pressure, hyperlipidemia, smoking habits, pain in the chest, EF, dyspnea, mortality rate due to heart problems and other factors including quality of life) and angiography results were used as the patients information. Primary angiography to check the patient s condition was taken as the start point. Categorizing the patients in CABG and MFU was taken as the initial event and death was taken as final event. Survival analyses were carried out using Kaplan-Mieir and Cox-Log rank test. Reference group for obtaining group risk ratio is the group with minimum risk. Data analysis was performed in STATA v.12 with sig. = Findings Men and women constituted 78% (n = 231) and 22% (n = 65) of the sample group respectively. CABG and MFU were performed on 50.7% (n = 150) and 49.3% (n = 146) of the participants. Average age of MFU and CABG groups were 61.74±9.02 and 61.07±9.14 respectively. Over the five years follow up period, 14 deaths (9.3%) was recoded in CABG group including 10 men (71.4%) and 4 women (28.6%). In addition, 35.7% of the CABG group were diabetics, 50% had high blood pressure, 21.4% had hyperlipidemia, and 42.9% used to smoke. In addition, 28 deaths (19/2%) were recorded in MFU group out of which 19 (67.9%) were men and 9 (32.1%) were women. Moreover, 42.9% of MFU group were diabetic, 46.4% suffered from high blood pressure, 42.9% had hyperlipidemia, and 42.9% used to smoke. Totally, 108 participants (35.5%) were diabetics, 140 (43.7%) suffered from high blood pressure, 88 (29.7%) had hyperlipidemia, 110 (n=37.2%) used to smoke), 2 (0.7%) had record of stroke, and 1 (0.3%) had peripheral vessels disease. Results analysis showed that demographic specifications such as age, gender, diabetes, high blood pressure, and smoking habits were not significantly effective on clinical outcomes; while they

3 A comparative survey of cardiac parients with 3VD and sever ventricular heart failure under CABG were effective on emergence of coronary artery problems. Survival time measured from CABG and initiation of MFU. Variable Value CABG MFU Frequency (%) Frequency (%) This means that mortality rate in MFU was 2 times more than that of CABG group. Diagrams 1 and 2 represent survival function of CABG and MFU patients based on Kaplan-Mieir method with adjustment of secondary variables. Gender Female 116(77.3) 115 (78.5) Male 34 (22.7) 31 (21.2) (4) 4 (2.7) (27.3) 39 (26.7) Age group (39.3) 51(34.9) (22) 42 (38.8) (7.3) 10 (6.8) Diabetic Smoking habits High blood pressure Hyperlipidemia Negative 97 (64.7) 94 (64.6) Positive 53(35.3) 93 (63.7) Negative 93(62) 93 (63.7) Positive 57 (38) 53 (36.3) Negative 77(51.3) 79(54.1) Positive 73(48.7) 67 (45.9) Negative 117(78) 91(62.3) Positive 33(22) 55(37.7) Table 1: Number and percentage of the patients in the study. One month, six months, one year, and three years survival of the CABG patients were 96.7%, 95.3%, 94.7%, and 89.8% respectively and in the case of MFU, these figures were 97%, 92.5%, 86.3%, and 83.4% respectively. In addition, average survival time of MFU and CABG patients were 52.8±1.64 and 57.18±1.23 months respectively. Mid of survival time in the both groups was 75 months. The results showed that mortality rate with error level of 0.05 was significantly related to the type of medical intervention (p-value = 0.012). Diagram 2: Survival of MFU patients with adjustment of secondary variables. Diagrams 3 and 4 represent risk rate of CABG and MFU patients based on Cox relative risk model. Clearly, risk rate in CABG and MFU patients increases after 30 and 20 months. Diagram 3: Accumulated risk rate of CABG based on Cox model. Diagram 1: Survival of CABG patients with adjustment of secondary variables. Diagram 4: Accumulated risk rate of MFU based on Cox model.

4 2040 Khosro Farhadi, Hamidreza Shetabi et Al To obtain goodness of fit of the model with the survival data, the effective variables on survival time of the patients were determined using ranked logarithmic test. Afterward, all the significant variables and the insignificant variables with p- value<0.25 were added to Cox model. The effect of disturbing factors was cut step by step and the final model was obtained by determining the independent factors effective on survival of individual. According to rank-lag statistics, EF of the left main was significant (p-value<0.001). Cox test was carried out as one/multi-variable test on gender, age (ranges), diabetes, high blood pressure, smoking habit, hyperlipidemia, and EF of left main. The effect of key disturbing variables and the effective variables on survival time of the individual can be controlled and obtained using Cox regression. The model showed that EF of left main was a significant variable. Discussion The present study is one of the few retrospective cohort studies on comparing survival of the patients after CABG and MFU interventions. The data was analyzed using survival analysis. It is notable that majority of studies in this field have relied on death event frequency comparison. An advantage of survival analysis is that as far as the patients are traceable, they can influence the results; therefore, the lost cases have a small effect on the results. Totally, 150 CABG patients and 146 MFU patients were followed up from one month to 60 months. Descriptive specifications of the patients is listed in Table 1. Average age of the patients was 41.4±9.07 years, which is similar with that of Rasoulinejad s study (60±11.8 years). To determine the relationship between survival term and independent variables, Cox regression was used and EF of left main was the only significantly effective variable on survival time. One month, six months, one year, and three years survival of CABG patients was 96.7%, 95.3%, 94.7%, and 89.8% respectively and these figures for the pharmaceutical medication patients were 97%, 92.5%, 86.3%, and 83.4% respectively. In addition, mean survival time of MFU patients was 52.80±1.64 months and that of CABG patients was 57.15±1.23. Mean survival time in the two groups was 75 months. Survival expectancy in our study was higher. Consistent with OConnor and Mikleborought (7, 8), the results showed a relationship between low EF of left main and high rate of mortality; no such relationship was reported by Torabian. Four years survival of MFU and CABG groups was 79% and 89% respectively. Velazquez (9) studied 624 MFU and 139 CABG patients in the Netherlands and reported survival rate in five years equal with 54% and 71% in MFU and CABG groups respectively. He also reported acceptable improvement of the symptoms in CABG group. PAOLO (10) studied 302 coronary vessels diseases with EF < 35% under CABG treatment in Italy and reported average survival time of 63±4% in a 10 years survey. A study in 1998 in the USA titled comparing three-year survival after CABG and angioplasty showed that survival rate after angioplasty (95.3%) was significantly higher than that of CABG (92.4%) (11). Conclusion Although, some of the studies have reported ineffectiveness of CABG on functional capabilities of the patients, effectiveness of the treatment on quality of life of the patients is undeniable. Apparently, our results, which are consistent with most of other studies, are acceptable and survival rate in CABG group is higher than that of MUF only group. In addition, improvement of the symptoms, quality of life, and contraction capability of the heart with by CABG treatment are more satisfactory. References 1) Murray CJ, Lopez AD. Global burden of disease: Harvard University Press Cambridge, MA; ) Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. The American journal of medicine. 2004; 116(10): ) Parry M, Watt-Watson J. Peer support intervention trials for individuals with heart disease: A systematic review. European Journal of Cardiovascular Nursing. 2010; 9(1): ) Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, Schönberger JP, et al. Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. New England Journal of Medicine. 2001; 344(15): ) Efron B. The efficiency of Cox s likelihood function for censored data. Journal of the American statistical Association. 1977; 72(359): ) Klein JP, Moeschberger ML. Censoring and truncation. Survival Analysis: Techniques for Censored and

5 A comparative survey of cardiac parients with 3VD and sever ventricular heart failure under CABG Truncated Data. 2003: ) O Connor GT, Plume SK, Olmstead EM, Coffin LH, Morton JR, Maloney CT, et al. A regional prospective study of in-hospital mortality associated with coronary artery bypass grafting. Jama. 1991; 266(6): ) Mickleborough LL, Takagi Y, Maruyama H, Sun Z, Mohamed S. Is sex a factor in determining operative risk for aortocoronary bypass graft surgery? Circulation. 1995; 92(9): ) Velazquez EJ, Williams JB, Yow E, Shaw LK, Lee KL, Phillips HR, et al. Long-term survival of patients with ischemic cardiomyopathy treated by coronary artery bypass grafting versus medical therapy. The Annals of thoracic surgery. 2012; 93(2): ) Nardi P, Pellegrino A, Scafuri A, Colella D, Bassano C, Polisca P, et al. Long-term outcome of coronary artery bypass grafting in patients with left ventricular dysfunction. The Annals of thoracic surgery. 2009; 87(5): ) Hannan EL, Racz MJ, McCallister BD, Ryan TJ, Arani DT, Isom OW, et al. A comparison of three-year survival after coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Journal of the American College of Cardiology. 1999; 33(1): Acknowledgement This study is a part of research plan No ; the author express their gratitude for financial supports by Research Department of Kermanshah Medical Science University. Corresponding author SOUDABEH ESKANDARI MSc of biostatistics, Biostatistics and Epidemiology Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah s.eskandari@kums.ac.ir (Iran)