The mean age of the patients treated with aspirin was 60.9±11.05, and the mean age of the patients treated with aspirin and clopidogrel was 60.48±9.8. According to t-test, the difference in age between the two groups was not statistically significant (p=0.78). In the aspirin group, 42.9% of the patients and, in the aspirin plus clopidogrel group, 45.7% of the patients were younger than 60 years old. The rest of the patients of the two groups were older than 60 years old. The difference in age distribution between the two groups was not statistically significant according to a chi-square test (P=0.73).

The mean BMI in the group treated with aspirin was 27.3±4.2 and in the group treated with clopidogrel + aspirin, was 28.3±10. According to t-test, the difference in mean BMI was not statistically significant between the two groups (p=0.46). In the aspirin group, the mean EF of the patients was 46.5±10.9 percent and, in the aspirin plus clopidogrel group, was 46.2±9.2 percent, which difference was not found to be statistically significant (p=0.86). None of the patients in both groups were HIV positive or HCV positive.

Based on chi-square test, the difference in the need for blood transfusion in the studied groups during the first 24 hours after surgery was not statistically significant (p=0.8). (Table 1)

Table 1: The difference in the need for blood transfusion in the studied groups during the first 24 hours after surgery

* “N” represents the number of patients in each group
** Statistical test: Chi-Square test

Additionally, according to the above table, the difference in the need for blood transfusions during hospital stay was not statistically significant between the group receiving aspirin (91.4%) and the group receiving aspirin + clopidogrel (87.1%)(p=0.41) (Table 2).

Table 2: The difference in the need for blood transfusion in the studied groups during hospital stay

* “N” represents the number of patients in each group
** Statistical test: Chi-Square test

According to the results of a repeated measures, test differences in bleeding in each group over time was statistically significant (time effect). But the difference between the two groups was not statistically significant in any of the times (24 hours after surgery and until the removal of the drain) (group effect and the time-group interaction were not statistically significant either) (p=0.9). According to an independent t-test, the difference in the mean bleeding during the first 24 hours after surgery was not statistically significant in both groups receiving aspirin and clopidogrel + aspirin (p=0.067). Although the amount of bleeding in the group receiving aspirin + clopidogrel was more than the aspirin group, this difference was not statistically significant. Despite the fact that the group receiving aspirin + clopidogrel had more bleeding until the removal of the drain in comparison with the group receiving aspirin, this difference was not statistically significant as determined by a t-test (p=0.27).

The mean duration of ICU stay for the group receiving aspirin was 53.12 hours and in the group receiving aspirin + clopidogrel, it was 50.35 hours. This difference was not statistically significant (p=0.51).

The mean duration of drain use in the aspirin group was 106.2 hours and it was 107.4 hours in the group receiving aspirin + clopidogrel, but this difference was not statistically significant as determined by a t-test (p>0.05).

In the group receiving aspirin, 3 patients (4.3%) and, in the group receiving aspirin + clopidogrel, 6 patients (8.6%) needed reoperation, but this difference was not statistically significant, according to Fisher’s exact test (p=0.24). (Table 3)

Table 3: The difference in the need for need for reoperation in the studied groups

* “N” represents the number of patients in each group
** Statistical test: Fisher’s exact test

In both groups, the average number of days of hospital stay was 6.5 days and the t-test showed no statistically significant difference in the number of days of hospitalization in the two groups. Based on the obtained results, the difference in the mean values of blood parameters before the surgery was not statistically significant (p > 0.05). Additionally, based on the results of an independent t-test, the differences in values of lipid profile, renal function and CRP indexes were not statistically significant in the two groups before the surgery (p > 0.05). (Table 4)

Table 4: The Comparison of mean and standard deviation of laboratory indices before the surgery in studied groups


Table 5- The Comparison of mean and standard deviation of laboratory indices in studied groups at discharge


According to a t- test, the mean values of Hb, HCT, PLT and BUN was significantly higher at discharge in the group receiving aspirin than in the group receiving aspirin + clopidogrel. (Table 5).

Based on a t-test, there was no significant difference between the mean injected platelet units for the studied groups during hospital stay (p=0.47). The mean FFP received during hospital stay was significantly higher in the group receiving aspirin + clopidogrel than in the group receiving aspirin (p=0.0009). Additionally, the mean amounts of the packed cells received during hospitalization was higher in the group receiving aspirin + clopidogrel than in the aspirin group. But this difference was not statistically significant (p=0.068). 75.7% of the patients receiving aspirin and 80% of the patients receiving aspirin + clopidogrel needed to receive FFP during hospitalization. According to a chi-square test, this difference was not statistically significant (p=0.54). None of the patients in either group needed receiving whole blood during hospitalization. The mean postoperative bleeding at various times after surgery and Hb and HCT amounts did not show any significant difference in the aspirin-receiving group in various age groups (p > 0.05). The need for blood transfusions in younger than 60 patients in the aspirin group was 83.4% and in the older than 60 patients was 97.5% and according to Fisher’s exact test, this difference was statistically significant (p=0.036). Moreover, the difference in the amount of postoperative bleeding, hemoglobin and hematocrit in patients receiving aspirin + clopidogrel was not statistically significant in terms of age groups (under 60 and 60 years and older). 81.3% of the patients younger than 60 years and 92.1% of the patients 60 years and older who received aspirin + clopidogrel needed post-operative blood transfusions. Fisher’s exact test did not show a significant difference between these groups (p=0.17).

Differences in the frequency distribution of the number of grafts in both groups was statistically significant (p=0.022), but the mean number of grafts was not statistically significant (p=0.07).

DISCUSSION

Studies published in 1990 and 1991 indicated that the administration of aspirin preoperatively leads to further surgeries due to increased postoperative bleeding (6.6 vs. 1.7% and 6.3 vs. 2.4% in two studies) (8, 9). In subsequent studies, however, no increase in bleeding was observed. The administration of aspirin could even decrease mortalities in hospitals (10-12). In the past, concerns about bleeding lead physicians to advise patients undergoing CABG to discontinue taking aspirin three to five days before surgery. However, this general view is not recommended any more. ACCF/AHA2011 instructions recommend continuing to take aspirin or starting it before CABG surgery (13). Anemia is an independent risk factor predisposing complications and mortality after CABG. As a result, the transfer of red blood cells (RBC) is common. Blood transfusion rates have been reported to be between 40% and 90% (14). In the present study, this amount was 91.4% vs. 87.1% which was lower in the aspirin + clopidogrel group, but the difference was not statistically significant. As reported in 2010, among more than 82,000 patients from hospitals in the United States who had undergone CABG surgery with cardiopulmonary bypass in 2008, the rate of blood transfusions during surgery was 56.1% (15). In addition, the bleeding which requires re-surgery was associated with a strong need for blood transfusions, and longer ICU and hospital stays. The re-surgery rates ranged from 4% to 6% (16). However, a study has shown that during 1995-1997, there has been a reduction in the rates of re-operation down to 2% (17). In the present study too, the need for repeated OR in the aspirin receiving group was less than half of the group receiving aspirin + clopidogrel. However, this difference was not statistically significant (3.4%vs. 6.8%).

Previous randomized trials have examined dual antiplatelet therapy with aspirin + clopidogrel in cardiovascular patients. There has been observed no clinical benefits in two studies that investigated combined antiplatelet treatment as compared with aspirin alone for patients with risk factors for atherosclerosis, cerebral, cardiac or peripheral vascular disease (18, 19). On the contrary, the combination of clopidogrel and aspirin as compared with aspirin alone has demonstrated significant improvements in the outcome of patients undergoing percutaneous vascular intervention (20), and in patients with acute coronary syndrome (21-23). In our study too, no benefits were observed in the group receiving aspirin + clopidogrel. Moreover, the aspirin group showed significantly lower postoperative bleeding (834.67±595.81 vs. 662±506.39). Also, in the group receiving aspirin the mean values of Hb, HCT, BUN, and blood platelets at discharge were significantly higher than the group receiving aspirin + clopidogrel. Additionally, the mean amount of received FFP and the need for injections were lower in the aspirin group patients than the group receiving aspirin + clopidogrel (97.5 vs. 83.13%, p=0.0009). If the above criteria be considered as indicating a good prognosis, the group receiving aspirin had a better prognosis.Often surgeons prescribe clopidogrel commonly after CABG, believing that it prevents graft occlusion, and possibly improves clinical outcomes (24, 25). Although prospective randomized controlled trial data in this area is inadequate (24), previous studies cited in cardiac surgery literature have suggested that clopidogrel may improve postoperative outcomes (25-27). In a study of off-pump CABG patients, Ebrahimi et al demonstrated that adding clopidogrel to aspirin was accompanied with a tendency toward improvements in SVG remaining open up to 6 months after surgery (26). Recently, Gao et al have reported the results of a non-randomized trial in which 197 patients received 75 mg clopidogrel plus 100 mg aspirin the day after surgery based on a weekly replacement therapy. Within 7 days, the risk of life-threatening events or major bleeding after CABG surgery did not show a significant increase in patients receiving clopidogrel 5 days prior to CABG (9.6% vs 6.3% with placebo), but the same was not true for patients who had discontinued clopidogrel five days or more before CABG (4.4% vs. 5.3%) (29). These findings are supported by several other observational studies (30-37). In our study too, adding aspirin to clopidogrel did not lead to significant differences in life-threatening events, which confirms the cited studies. However, in a study by Wang et al, there was observed a good response to adding clopidogrel to aspirin after CABG (38).

CONCLUSION

Given the obtained results in the present study, the following conclusions can be drawn:

1. The amount of postoperative bleeding in the clopidogrel + aspirin was more than the aspirin group. However, its P Value is not significant, but it approaches the significance level (p=0.067).
2. The platelet, Hb, and HCT is lower at discharge in the clopidogrel + aspirin group than in the aspirin group, the cause of which is higher blood loss in the aspirin + clopidogrel group in comparison with the aspirin group.
3. FFP use in the aspirin + clopidogrel group was more than in the aspirin group which is due to increased blood loss in the first group (p=0.000).
4. To get more accurate results, further research is recommended with larger sample numbers.
5. Considering the importance of the drugs aspirin and clopidogrel in the prevention of heart attacks and their importance in the health system, it is recommended that the benefits of these drugs be not overlooked in comparison with their possible disadvantages.