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NewsletterLiterature Review Aspirin and Mortality from Coronary Artery
Bypass Surgery Dennis T. Mangano, PhD, MD, for the Multicenter Study of Perioperative
Ischemia Research Group
Antiplatelet therapy is currently a mainstay of primary and secondary prevention in patients with acute and chronic cardiovascular disease. Early administration of aspirin within 24 hour of coronary artery bypass surgery (CABG) is recommended in the American College of Cardiology and American Heart Association practice guidelines for CABG surgery to decrease the risk of saphenous vein graft occlusion (Circulation 1999;100:1464). However, perceived concerns about the safety of aspirin therapy in surgical patients may limit its widespread use in the early postoperative period. Some studies have demonstrated that preoperative aspirin therapy increased the risk of postoperative bleeding and may prompt some to discontinue aspirin prior to operation, administer prophylactic antifibrinolytic agents during operation, or transfuse platelets. At present, additional information would be useful for guiding the use of aspirin therapy in surgical patients in order to balance its cardiovascular protective effects with its potential risks. Dr. Mangano et al. conducted a prospective study to determine the incidence of fatal and nonfatal ischemic events involving the heart, brain, kidneys and gastrointestinal tract after coronary artery bypass surgery comparing patients treated with aspirin within 48 hours of surgery and those not treated with aspirin. The study was prospective and longitudinal involving 5,065 patients undergoing coronary artery bypass surgery at one of 70 institutions in 17 countries, but did not randomize patients according to treatment with aspirin. To be eligible for enrollment, each patient had to be scheduled to undergo coronary artery bypass grafting with the use of cardiopulmonary bypass, had to be able to complete the preoperative interview and could not be enrolled in another study or clinical trial. Outcomes 48 hours after surgery were classified as cardiac, cerebral, renal, gastrointestinal or other. Of the 5,065 patients involved, 3,001 (59.2%) received aspirin ranging from a dose of 80 to 650mg in the first 48 hours after revascularization. Adverse results caused by ischemia and all potential side effects associated with aspirin use including blood loss, gastric irritation, infection and impaired wound healing were recorded. A chi-square test was used to compare the incidence of death and adverse outcomes in patients who had received aspirin with those who had not received aspirin. A total of 164 (3.2%) of the 5065 patients died during the index hospitalization and 100% of deaths were associated with one or more ischemic events. Patients who had received aspirin within 48 hours of revascularization had only one-third the risk of dying compared to those who did not received aspirin (1.3% v. 4.0%, p<0.001). Their risk of non-fatal ischemic complications involving the heart, brain, kidneys or gastrointestinal tract was about 60% of that among patients who had not received aspirin. The reduction in combined mortality and morbidity was 43%. The survival rate throughout hospitalization was greater and hospital length of stay less by two days in those who had received aspirin. No other factor including any medication was associated with reduced rates of ischemic complications after surgery. Of note, no dose effect of aspirin was found for either fatal or nonfatal outcomes with total doses ranging from 75 mg to 650 mg per day. Aspirin therapy was not associated with any increased risk of bleeding, gastritis, infection or impaired wound healing. In addition to aspirin therapy, the study provided further evidence to support a fundamental role of platelets in postoperative ischemic complications after coronary bypass surgery. Subgroup analysis demonstrated that patients who had aspirin discontinued prior to operation, platelet transfusions during operation, or prophylactic antifibrinolytic therapy also had an increased risk of death and ischemic complications. However, within each of the subgroups, the risk of death was less in patients who received aspirin within 48 after operation. The authors suggested that the benefits of aspirin may be explained by both its anti-inflammatory actions and its anti-thrombotic actions serving to attenuate the pathophysiologic action of platelets in the etiology of postoperative organ injury. This study by Mangano et al. adds to the body of literature supporting a beneficial effect of aspirin therapy. An unexpected finding of this multinational study was that 40% of patients undergoing elective coronary artery bypass surgery were not administered aspirin within 48 hours after surgery despite the ACC/AHA practice guidelines that advocate aspirin use to maintain bypass graft patency. It would be of interest to know the reasons for withholding early postoperative aspirin in the group that did not receive aspirin. Despite the potential for adverse effects based on the known pharmacologic actions of aspirin, immediate post-operative aspirin administration was not associated with increased risk of hemorrhage, renal insufficiency, gastritis, or other complications. In conclusion, based the established safety, affordability and availability of aspirin, a strong argument can be made for the expanded use of aspirin after coronary bypass surgery. In addition, perceived contraindications to aspirin therapy such as thrombocytopenia, coagulation disorders, renal insufficiency, history of gastritis or peptic ulcer disease, or postoperative bleeding may need to be re-examined. Further studies may be necessary to determine the best dose and optimal timing of administration. Finally, early postoperative aspirin therapy may be beneficial also in patients undergoing cardiac operations not confined to coronary artery bypass grafting or other vascular surgical patients who are also at risk for postoperative ischemic events. Table of Contents:
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