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Ann Thorac Surg 2003;76:41-45
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Effect of preoperative aspirin use in off-pump coronary artery bypass operations

^a Department of Cardiothoracic Surgery, Liverpool, United Kingdom
^b Department of Research and Development, The Cardiothoracic Centre, Liverpool, United Kingdom

Accepted for publication January 17, 2003.

^* Address reprint requests to Mr Dihmis, Consultant Cardiac Surgeon, The Cardiothoracic Centre-Liverpool, Thomas Drive, Liverpool L14 3PE, United Kingdom.
e-mail: wdihmis{at}ccl-tr.nwest.nhs.uk

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
BACKGROUND: The effect of preoperative aspirin use until the day of operation on mortality rate and bleeding risks in patients who had on-pump coronary artery bypass operation has been well documented. However, the effect of aspirin use in patients undergoing off-pump coronary artery bypass operation (OPCAB) with regard to postoperative blood loss and morbidity has not been studied. We aimed to determine the effects of continuing aspirin therapy preoperatively.

METHODS: We performed a retrospective study of 340 patients who had first-time OPCAB between January 1998 and September 2001. A propensity score for receiving aspirin until the day of operation was constructed from core patient characteristics. All aspirin users (n = 170) were matched with unique 170 nonaspirin users by identical propensity score. The primary outcome measures were in-hospital mortality rate and hemorrhage-related outcomes (postoperative blood loss in the intensive care unit, reexploration for bleeding, and blood product requirements). Secondary outcome measures were stroke, myocardial infarction, gastrointestinal bleeding, and sternal wound infections.

RESULTS: There were no differences in patient characteristics between aspirin users and nonaspirin users. The average postoperative blood loss (845 mL versus 775 mL; p = 0.157) and the rate of reexploration for bleeding (3.5% versus 3.5%; p > 0.99) were similar in aspirin users and nonaspirin users. We found no significant difference between blood product requirements for the two groups. Similarly, we found no significant difference in the incidence of the secondary outcomes.

CONCLUSIONS: Preoperative aspirin did not increase bleeding-related complications, mortality rate, or other morbidities in patients who had off-pump coronary artery operation.

	Introduction

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Aspirin has been a double-edged sword in cardiac operation since it became an essential part of management for patients with coronary artery disease. Aspirin has been shown to effectively increase survival and reduce morbidity in patients with ischemic heart disease [1–4]. The question whether aspirin should be continued during the preoperative period to the day of coronary operation has been the subject of many trials, and their results are conflicting.

Preoperative aspirin continued to the day of operation or administrated during the early postoperative period has been shown to result in improved early graft patency [5–7]. Aspirin use during the perioperative and postoperative period has also been shown to improve the late patency of vein grafts [7, 8]. These decisive advantages have been countered by studies showing that continued aspirin during the preoperative period could increase the postoperative blood loss in patients who have on-pump coronary artery bypass grafting (CABG) [5, 9]. However, this has been challenged by other reports [10, 11]. Dacey and colleagues [11], on behalf of the Northern New England Cardiovascular Disease Study Group, have shown a decreased risk of in-hospital death in CABG patients without significant increase in hemorrhage, blood product requirements, or related morbidity when aspirin therapy was continued to the day of operation.

All these studies have been conducted on patients receiving conventional on-pump CABG. With the increase in off-pump CABG (OPCAB), it is necessary to determine the effect of continued aspirin use on adverse outcomes after OPCAB operation. A recent survey showed a lack of uniformity in practice in the United States [12], thus emphasizing the importance of this study. This study aims to determine the effect of continued aspirin use before OPCAB operation on mortality rate, bleeding, and other related in-hospital morbidities.

	Material and methods

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Patient population and data
We performed a retrospective study of 340 propensity-matched patients who had first-time OPCAB at the Cardiothoracic Center-Liverpool between January 1, 1998 and September 30, 2001. Aspirin use was defined as ingestion up to the time of operation. The exclusion criteria were previous cardiac operation, warfarin therapy, hepatic disease, and treatment with other antiplatelet agents such as clopidogrel or dipyridamole. Patients who were converted from OPCAB to on-pump operation were not included in this study.

We identified a total of 170 consecutive patients who continued taking aspirin therapy within 7 days before OPCAB operation during the study period (aspirin users). We propensity-matched (see Statistical Analysis) these patients to 170 unique patients who had OPCAB operation but whose aspirin therapy was stopped a week before operation (nonaspirin users).

Procedure and definitions
Preoperative dose of aspirin varied from 75 to 300 mg. Routine anesthetic premedication and induction techniques were used but not standardized. None of the patients received trasylol or any other antifibrinolytic agents. The patients were heparinized for an activated partial thromboplastin time greater than 280 seconds. The surgical technique for OPCAB was standardized with the use of the Octopus II plus for stabilization and the routine use of intracoronary shunts while performing the anastomoses. There was liberal use of arterial grafts.

All patients had mediastinal and pleural drains if the pleura was breached. The drains were left in situ until drainage was less than 20 mL for 2 consecutive hours after a period of 12 hours. If the blood loss was more than 400 mL in the first hour, 300 mL/hour in the first 2 hours, 200 mL/hour in the first 3 hours, or more than 1 L in the first 4 hours the patients were reexplored. Shed blood was recovered using standard cell salvage equipment if the loss was more than 600 mL. Blood transfusion was indicated if the hemoglobin level was less than 7.5 g/dL. The average postoperative stay was 7 days and intensive care unit stay was 12 hours.

All data were collected prospectively during the patient admission and entered onto the Cardiac Surgery Database as part of routine clinical practice. Methods of data collection and definitions have been published previously [13]. Data were collected on the following variables: age, sex, body mass index, urgency of operation, angina class, New York Heart Association functional class, smoking, diabetes, hypercholesterolemia, hypertension, peripheral vascular disease, cerebrovascular disease, respiratory disease, renal dysfunction, the extent of coronary disease, and left ventricular ejection fraction. The number of grafts and use of the left internal mammary artery were also recorded. The primary outcome measures were in-hospital mortality rate and hemorrhage-related outcomes (postoperative blood loss in the intensive care unit, reexploration for bleeding, and blood product requirements of red blood cells, platelets, and fresh frozen plasma). Secondary outcome measures of stroke, myocardial infarction, gastrointestinal bleeding, and sternal wound infection were also recorded.

In-hospital death was defined as death during the same hospital admission regardless of cause. All patients transferred from the base hospital to another hospital were followed up to confirm their status at discharge. Reexploration for bleeding was defined as bleeding that required surgical reoperation after initial departure from the operating theater. Upper gastrointestinal bleeding was defined as documented evidence of hematemesis or melena confirmed by a decrease in hemoglobin. Postoperative stroke was defined as a new focal neurologic deficit and comatose states occurring postoperatively that persisted for more than 24 hours after its onset and was noted before discharge. We excluded confused states, transient events, and intellectual impairment to avoid any subjective bias. Postoperative myocardial infarction was defined as a new Q-wave postoperatively in two or more contiguous leads on an electrocardiogram or significant increase in postoperative cardiac enzyme levels combined with hemodynamic and electrocardiographic evidence of myocardial infarction. Criteria for defining sternal wound infections were in accord with the published evidence-based guidelines by the Centers for Disease Control and Prevention [14].

Blood product requirements
Blood transfusion data were obtained from the local blood transfusion service, which is provided routinely on a monthly basis. These data consisted of date of request for red blood cells and number of units used, along with the number of fresh frozen plasma and platelet units used during the patient’s hospital admission. The number of units used, if any, was calculated by summation across the patient’s postoperative length of stay.

Statistical analysis
To match aspirin users with unique nonaspirin users, logistic regression [15] was used to develop a propensity score for aspirin use for all patients who had OPCAB [16]. The propensity score included age, sex, body mass index, insulin-dependent diabetes, peripheral vascular disease, respiratory disease, renal dysfunction, left ventricular ejection fraction, extent of disease, and emergency operation [17]. The C statistic, which is equivalent to the receiver operating characteristic curve, for this model was 0.68 [18]. Aspirin users were matched with nonaspirin users who had an identical five-digit propensity score. If this could not be done, we then proceeded to a four-, three-, two-, or one-digit match [19].

Continuous variables are shown as median with 25th and 75th centiles, and categorical variables are shown as a percentage with 95% confidence intervals. Comparisons were made with Wilcoxon rank sum tests and ² tests as appropriate. Because of the low blood product requirements in aspirin and nonaspirin users, transfusion data are shown as median and mean with standard deviation. In all cases a p value less than 0.05 was considered statistically significant. All statistical analyses were performed retrospectively with SAS for Windows Version 8.2 (SAS Institute, Cary, NC).

	Results

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The patient and disease characteristics of the propensity-matched aspirin and nonaspirin users are shown in Table 1. Both groups were well matched, with the only significant difference being that patients on aspirin had a higher severity of angina (p < 0.001).

There were no significant differences between aspirin and nonaspirin users in in-hospital mortality rate, postoperative blood loss, reexploration for bleeding, gastrointestinal bleeding, stroke, and myocardial infarction (Table 2). Aspirin users had a higher incidence of sternal wound infection than nonaspirin users, although this difference just failed to reach statistical significance (p = 0.054, Table 2). There was a statistically significant difference in postoperative length of stay despite the median being the same in both groups; this difference was due to differences in distributions, with aspirin users having a high interquartile range (6 to 9 days compared with 5 to 8 days; p < 0.001).

	Comment

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The issue of aspirin therapy and on-pump operation has been debated extensively in the literature. The argument to continue aspirin to the day of operation comes from evidence showing that it increases early graft patency rates in patients who had coronary artery operations [5, 7]. But the same studies and other research showed that aspirin therapy was associated with increased postoperative blood loss [5, 9]. Interest was renewed when a recent paper by the Northern New England Cardiovascular Disease Study Group demonstrated no increase in blood loss and more importantly a decisive survival advantage in patients who had on-pump operations with continued aspirin treatment [11]. There is increasing evidence that continued use of aspirin is beneficial for reducing early and late graft failure [5–7] and improving mortality rates [11] with no difference in morbidity rates [11, 20].

All those studies were done using patients who had on-pump coronary artery operations. A major inflammatory response is seen in patients who have on-pump operation [11]. Bypass pumps, reperfusion injury, stunning of enzyme complexes by hypothermia, and heparin-protamine complex–induced reaction are some reasons for the massive inflammatory response in those patients. This inflammatory response is believed to contribute to poor outcomes after cardiac operation. It has been shown that by virtue of its antiinflammatory action, aspirin may exert a protective effect and thus help downregulate the inflammatory response [11].

The effect of aspirin on off-pump coronary artery operation has not been investigated. There are significant differences in terms of causative insults to the inflammatory and coagulation system when comparing OPCAB with on-pump CABG. Hence this is a completely uncharted territory. The benefit of continuing aspirin is evident from numerous studies [5–7, 9, 11]. We attempted to address the criticism against aspirin therapy continued in the preoperative period, namely, the possible increase in postoperative blood loss.

Our study shows that the use of aspirin continued preoperatively does not increase postoperative blood loss, blood product requirements, and resternotomy rates in off-pump coronary artery operation patients. We have also demonstrated that mortality is similar between the two groups.

In addition, other morbidities, including myocardial infarction, stroke, and upper gastrointestinal hemorrhage, were not significantly increased in patients taking aspirin. This is similar to results of previous studies of patients who had cardiopulmonary bypass [9]. Superficial sternal wound infection was the only postoperative morbidity that came close to being statistically significant, with absolute numbers being nearly four times higher. There were no patients with deep sternal wound infections. We postulate that this increase in superficial wound infections could be attributed to the increase in risk of wound hematoma as a result of continued aspirin therapy.

When compared with nonaspirin users, patients receiving aspirin until OPCAB operation did not have significantly increased blood loss. None of the patients received aprotinin. We have also shown that blood product requirements were small and not significantly different between the two groups. This low utilization of blood or blood products could be a result of different factors, such as high threshold for transfusion and the use of the blood salvage systems.

Internal mammary artery usage, increasing age, small body surface area, and increased distal anastomosis were shown to be independent risk factors for increased bleeding and resternotomy in on-pump CABG [21–23]. These variables are equally matched in both groups of patients in this study and did not make a significant difference in bleeding or resternotomy rates in OPCAB. When compared with studies on on-pump CABG, this study shows no difference in morbidity or mortality rates between nonaspirin users and aspirin users in OPCAB.

There are some limitations to our study. Retrospective studies cannot account for unknown variables that affect the outcomes of interest. Although propensity-matched studies are by far the best method of comparison in observational settings [16], they are not as powerful as randomized trials. However, they are more versatile and applicable to clinical settings than randomized studies. Although the history of aspirin ingestion was obtained, there were no measurements of salicylate levels in urine or preoperative bleeding time. We did not study long-term outcomes of aspirin use (eg, graft failure and symptom recurrence) because our aim was to investigate immediate postoperative events. With proven long-term benefits of on-pump CABG with aspirin, such outcomes will be of interest as our OPCAB experience grows.

In conclusion, continued aspirin use in off-pump coronary artery operation was not associated with increased risk of postoperative blood loss, blood product requirements, or resternotomy rates in patients who had off-pump coronary artery bypass grafting. In view of the unquestionable benefits of aspirin, especially regarding early graft patency, this study indicates that aspirin therapy should not be discontinued before off-pump coronary artery operation.

	Acknowledgments

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We acknowledge Miss Janet Deane, who maintains the quality of our cardiac surgery registry and ensures completeness of the data collected. Special thanks to Mr Eric Thorpe, Information Technology Manager from the Hematology Department at the Royal Liverpool University Hospital, for supplying the necessary transfusion data.

	References

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