Correspondence

Aspirin and Mortality from Coronary Bypass Surgery

N Engl J Med 2003; 348:1057-1059March 13, 2003

Article

To the Editor:

We were surprised to read, in the article by Mangano and colleagues (Oct. 24 issue),1 that the routine use of aspirin on the day of coronary bypass surgery is not the standard of care, given the 20-year-old evidence that starting aspirin therapy on the day of surgery results in a 50 to 70 percent reduction in early2 and late3 aortocoronary vein-graft occlusion. Our double-blind, randomized trial, published previously in the Journal, 2 led to the definition of early treatment with aspirin as a standard of care in the first American College of Chest Physicians–National Heart, Lung, and Blood Institute Consensus Conference report, in 1986.4 Early treatment with aspirin (within seven hours after surgery) did not increase bleeding, as measured by chest-tube blood loss, blood transfusion, or the need for reoperation for bleeding.2 Aspirin started later (on day 3 after surgery) did not reduce aortocoronary vein-graft occlusion.4 In vivo, isotope-labeled platelet deposition in vein grafts starts and progresses immediately after the initiation of vein-graft blood flow and is reduced with antiplatelet therapy before there is inflammation.5

Mangano and colleagues1 confirm that the antithrombotic standard of care for the past 20 years should be followed to reduce thrombosis and its associated cardiac and multiorgan complications. Unfortunately, this outcome could have been predicted, and aspirin should not have been withheld from any patient after coronary bypass surgery. Continuing aspirin before surgery for acute coronary syndromes or starting aspirin the day of elective coronary bypass grafting was not and is not taboo, contrary to the practices alluded to by Topol in his accompanying editorial.6

James H. Chesebro, M.D.
Mayo Clinic, Jacksonville, FL 32224
chesebro.james@mayo.edu

Valentin Fuster, M.D., Ph.D.
Mount Sinai Cardiovascular Institute, New York, NY 10029

Francisco J. Pugo, M.D.
Mayo Clinic Rochester, Rochester, MN 55901

6 References

1. 1

   Mangano DT. Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002;347:1309-1317
   Full Text | Web of Science | Medline

2. 2

   Chesebro JH, Clements IP, Fuster V, et al. A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency. N Engl J Med 1982;307:73-78
   Full Text | Web of Science | Medline

3. 3

   Chesebro JH, Fuster V, Elveback LR, et al. Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations. N Engl J Med 1984;310:209-214
   Full Text | Web of Science | Medline

4. 4

   Stein PD, Collins JJ Jr, Kantrowitz A. Antithrombotic therapy in mechanical and biological prosthetic heart valves and saphenous vein bypass grafts. Chest 1986;89:Suppl:46S-53S
   Web of Science | Medline

5. 5

   Fuster V, Dewanjee MK, Kaye MP, Josa M, Metke MP, Chesebro JH. Noninvasive radioisotopic technique for detection of platelet deposition in coronary artery bypass grafts in dogs and its reduction with platelet inhibitors. Circulation 1979;60:1508-1512
   Web of Science | Medline

6. 6

   Topol EJ. Aspirin with bypass surgery -- from taboo to new standard of care. N Engl J Med 2002;347:1359-1360
   Full Text | Web of Science | Medline

To the Editor:

Although the data presented by Mangano are of considerable clinical interest, we seriously doubt that the results necessarily support the conclusion that early postoperative use of aspirin improves outcomes after coronary-artery bypass grafting, for several reasons. First, treatment selection was not randomized, the decision when and whom to treat was not defined, and the investigation of the relation between early postoperative use of aspirin and outcome was, obviously, not planned prospectively. Second, the lower incidence of previous congestive heart failure in the aspirin-treatment group (30.3 percent, vs. 41.6 percent in the group that did not receive aspirin) and the higher rate of preoperative beta-blocker therapy (68.0 percent vs. 58.1 percent, respectively) clearly favors an improved outcome (independent of the early postoperative use of aspirin), because both factors are independent predictors of outcome after coronary-artery bypass grafting.1-3 Third, patients who did not receive early aspirin treatment were clearly sicker than those who did. A significantly greater proportion of the patients in that group (5.2 percent, vs. 1.9 percent of the group that did receive aspirin) were taken back to the operating room because of bleeding, thereby precluding the early oral administration of aspirin. The higher incidence of postoperative congestive heart failure may merely reflect the severity of their sickness, rather than a benefit of the early postoperative use of aspirin. Unfortunately, there is no information on the patients' characteristics immediately after surgery.

The data from this nonrandomized, uncontrolled investigation support the view that the early postoperative administration of aspirin is merely a surrogate measure of a favorable early postoperative outcome. Typically, only in patients without postoperative problems is the trachea extubated within 8 hours after surgery, and only these patients can begin to take oral aspirin within 24 to 48 hours after surgery. Patients who do not receive early aspirin are those who require prolonged mechanical ventilation or who present with bleeding.

Waheedullah Karzai, M.D.
Zentralklinik Bad Berka, Bad Berka, Germany
w.karzai.ana@zentralklinik-bad-berka.de

Hans-Joachim Priebe, M.D.
University of Freiburg, Freiburg, Germany

3 References

1. 1

   Van Caenegem O, Jacquet LM, Goenen M. Outcome of cardiac surgery patients with complicated intensive care unit stay. Curr Opin Crit Care 2002;8:404-410
   CrossRef | Medline

2. 2

   Weightman WM, Gibbs NM, Sheminant MR, Whitford EG, Mahon BD, Newman MA. Drug therapy before coronary artery surgery: nitrates are independent predictors of mortality and beta-adrenergic blockers predict survival. Anesth Analg 1999;88:286-291
   CrossRef | Web of Science | Medline

3. 3

   Ferguson TB Jr, Coombs LP, Peterson ED. Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America. JAMA 2002;287:2221-2227[Erratum, JAMA 2002;287:3212.]
   CrossRef | Web of Science | Medline

Author/Editor Response

My colleagues and I agree with Chesebro et al. that aspirin may reduce vein-graft occlusion; however, aspirin therapy immediately after bypass is not the standard of care. At our 70 centers (in 17 countries), only 15 percent of the patients received early treatment with aspirin. In 60 of the centers, the majority did not receive aspirin early, and in about one third none of the patients received aspirin early (Figure 1Figure 1Distribution of Study Centers According to the Early Use of Aspirin after Coronary Bypass Surgery.). All the patients enrolled in the study were randomly selected according to center, and about 10 percent of all bypass procedures are performed at these 70 centers. Clearly, concern about hemorrhage predominates, prompting preoperative discontinuation of aspirin (in 50 percent of our patients) and the use of “prothrombotic” therapies (in 73 percent). Therefore, Topol's impressions regarding the evolution of the standard of care, as expressed in his editorial, are correct and suggest that a consensus panel be organized to readdress the question of the early use of aspirin.1

In addition, we could not have predicted our findings and were surprised by their magnitude and breadth; no previous study had found any benefit in terms of survival, nor had any therapy proved effective against perioperative stroke or renal failure.

Karzai and Priebe suggest that the administration of aspirin must be delayed in patients who require ventilation. We disagree, since aspirin can be — and commonly is — administered by nasogastric tube or intravenously. Second, although acceptance of a therapy should be predicated on the results of at least one (and preferably two) randomized, controlled trials, we do not agree that the findings of observational studies serve little purpose. When properly performed, such studies provide unique insights into populations, risk, outcomes, paradigms of care, and the effects of consensus decisions — all of which are critical to trial design. Specifically, the findings of our observational study uncovered an important pattern associated with the early use of aspirin, one that might not have been suspected or otherwise addressed.

We believe that the associations discerned, as well as those proven insignificant, are noteworthy, since they were derived from comprehensive multivariate analyses based on 7500 data fields per patient, which also yielded consistent findings with respect to the discontinuation of aspirin, the transfusion of platelets, and the use of antifibrinolytic therapy — all of which are associated with worsened morbidity. Nor did isolated group differences confound our findings. In addition, as Topol elegantly states, we should not discount the compelling experiences with aspirin therapy in at-risk medical patients.

In conclusion, we are left with a dilemma, for our problem is potentially unsolvable. Aspirin is safe and inexpensive; it probably reduces vein-graft occlusion; it may reduce complications involving the heart, brain, kidney, and intestine; and no other therapy is available. Given these circumstances, can a randomized clinical trial, wherein one group is deprived of aspirin, even be performed? If not, the clinician must adjudicate, for each patient, the cost–benefit ratio for early aspirin therapy.

Dennis T. Mangano, Ph.D., M.D.
Ischemia Research and Education Foundation, San Francisco, CA 94134
dtb@iref.org

1 References

1. 1

   Stein PD, Collins JJ Jr, Kantrowitz A. Antithrombotic therapy in mechanical and biological prosthetic heart valves and saphenous vein bypass grafts. Chest 1986;89:Suppl:46S-53S
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Frantisek Bednar, Tomas Tencer, Petr Plasil, Zoltan Paluch, Lenka Sadilkova, Miroslav Prucha, Milos Kopa. (2012) Evaluation of Aspirin's Effect on Platelet Function Early After Coronary Artery Bypass Grafting. Journal of Cardiothoracic and Vascular Anesthesia
   CrossRef

2. 2

   Zanxin Wang, Fei Gao, Jianlong Men, Jing Ren, Paul Modi, Minxin Wei. (2011) Aspirin resistance in off-pump coronary artery bypass grafting. European Journal of Cardio-Thoracic Surgery
   CrossRef

3. 3

   Shahzad G Raja, Shamim Akhtar. (2011) Hypercoagulable state after off-pump coronary artery bypass grafting: evidence, mechanisms and implications. Expert Review of Cardiovascular Therapy 9:5, 599-608
   CrossRef