Correspondence

Beta-Blockade for Patients Undergoing Vascular Surgery

N Engl J Med 2000; 342:1051-1053April 6, 2000

Article

To the Editor:

Poldermans et al. (Dec. 9 issue)1 reported a reduction in the incidence of death and myocardial infarction after vascular surgery among patients who were pretreated with the beta-blocking drug bisoprolol, as compared with those who were not pretreated. Patients were included in the study if the results of dobutamine echocardiography were positive, indicating a high risk of complications of vascular surgery. The authors predicted that the perioperative event rate in this population would be 28 percent. Patients who did not receive beta-blockers were characterized as receiving “standard care.”

Beta-blocker therapy with atenolol before vascular surgery has been shown to reduce the incidence of cardiac events.2 Previous studies have suggested that coronary revascularization before vascular surgery in these high-risk patients may also decrease the number of perioperative events.3 Poldermans et al. excluded the highest-risk patients but still clearly selected a group at substantial risk.4,5 Treatment with alternative beta-blockers was not allowed, and there is no mention of the use of diagnostic coronary angiography, angioplasty, or surgical revascularization as part of standard care. The trial appears to have had a control group for which the outcome was expected to be poor, as compared with the outcome after beta-blocker therapy, rather than a control group that received care consistent with current practice. A control group in which risk stratification is followed by some further therapy may be a more realistic reflection of standard therapy with respect to the comparison with the bisoprolol group.

A second issue is the short-term outcome. The survival of patients undergoing vascular surgery who have positive stress tests is poor and is limited by their coronary artery disease.6 The study by Poldermans et al. focused on the immediate outcome of vascular surgery, to the exclusion of the longer term. A preoperative strategy that also considered therapy for the long term would be optimal in this high-risk population. Giving a beta-blocker preoperatively may be better than identifying patients at increased risk and then not offering them any therapy, but the results reported by Poldermans et al. do not identify the best therapy for patients with combined clinically significant coronary and vascular disease.

Ted Feldman, M.D.
Benjamin Fusman, M.D.
James F. McKinsey, M.D.
University of Chicago Hospital, Chicago, IL 60637

6 References

1. 1

   Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med 1999;341:1789-1794
   Full Text | Web of Science | Medline

2. 2

   Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 1996;335:1713-1720[Erratum, N Engl J Med 1997;336:1039.]
   Full Text | Web of Science | Medline

3. 3

   Hertzer NR. Basic data concerning associated coronary disease in peripheral vascular patients. Ann Vasc Surg 1987;1:616-620
   CrossRef | Medline

4. 4

   L'Italien GJ, Paul SD, Hendel RC, et al. Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1,081 vascular surgical candidates. J Am Coll Cardiol 1996;27:779-786
   CrossRef | Web of Science | Medline

5. 5

   Shaw LJ, Eagle KA, Gersh BJ, Miller DD. Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery. J Am Coll Cardiol 1996;27:787-798
   CrossRef | Web of Science | Medline

6. 6

   Eagle KA, Rihal CS, Foster ED, Mickel MC, Gersh BJ. Long-term survival in patients with coronary artery disease: importance of peripheral vascular disease. J Am Coll Cardiol 1994;23:1091-1095
   CrossRef | Web of Science | Medline

To the Editor:

The study by Poldermans et al. adds to the body of evidence that beta-blockade reduces perioperative morbidity and mortality from cardiac causes. Unlike Lee,1 who wrote the accompanying editorial, we do not believe that these results have “profound implications” regarding the assessment of preoperative risk.

In particular, Lee's statement that “exercise electrocardiography and other noninvasive tests for myocardial ischemia should not be used for perioperative risk stratification” is unsubstantiated. In fact, his position does not appear to be entirely consistent. Although he advocates stratification according to cardiac risk factors on the basis of clinical data, he later acknowledges that testing may be appropriate for “patients whose exercise tolerance is limited or whose clinical risk is unclear.” But it is precisely to clarify clinical risk in such patients that further testing is undertaken. Furthermore, patients with limited exercise tolerance constitute a large minority, if not the majority, of patients who are candidates for further screening. In practice, Lee's recommendations do not offer insight into how to use the results of Poldermans et al. to reduce the amount of testing used in risk assessment.

Of central importance in the study by Poldermans et al. was the exclusion of patients who were at the highest risk for adverse cardiac outcomes on the basis of noninvasive testing. Therefore, the identification of patients similar to the study participants, to whom the results apply, requires screening of the type that Lee discourages. Furthermore, Lee's conclusion that the cumulative morbidity resulting from cardiac catheterization, coronary revascularization, and major vascular surgery is likely to be higher than the 3.4 percent rate of major cardiac complications observed among patients in the study who were treated with beta-blockers requires further examination. This 3.4 percent rate is biased downward, because the study was stopped early. In addition, the small size of the study also implies that estimated rates would have a low level of precision. More important, comparison of this rate with another is not especially relevant, because current guidelines suggest that such interventions be undertaken only if they “significantly improve patients' long-term prognosis.”2

In summary, the results of Poldermans et al. do provide support for the increased use of beta-blockade as part of perioperative treatment but not for a change in screening practice.

Robert S. Litwack, M.D.
David M. Gilligan, M.D.
McGuire Veterans Affairs Medical Center, Richmond, VA 23249

Victor DeGruttola, Sc.D.
Harvard School of Public Health, Boston, MA 02115

2 References

1. 1

   Lee TH. Reducing cardiac risk in noncardiac surgery. N Engl J Med 1999;341:1838-1840
   Full Text | Web of Science | Medline

2. 2

   Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 1996;27:910-948
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Feldman and colleagues argue that the standard care given to patients in our control group was inconsistent with current practice, leading to an outcome that was expected to be poor, as compared with the outcome after beta-blocker therapy. They suggest that perioperative beta-blockade and prophylactic myocardial revascularization should have been part of standard care. We disagree and feel strongly that perioperative care in our control patients was consistent with the published guidelines of the American College of Cardiology and the American Heart Association.1

Before our study, perioperative beta-blockade had not been proved to alter the incidence of perioperative myocardial infarction and death from cardiac causes, although an effect on late postoperative cardiac events was demonstrated by Mangano et al.2 The guidelines of the American College of Cardiology and the American Heart Association state that “beta-blockers reduce perioperative ischemia and may ultimately be shown to reduce the risk of [myocardial infarction] and death. Clearly, this is an area where further research would be valuable.”1 Our study addressed this need. We did not use prophylactic myocardial revascularization as part of standard care because it is an unproven risk-reduction strategy. It is well recognized that the cumulative morbidity and mortality associated with coronary angiography, myocardial revascularization, and noncardiac surgery may exceed the risk associated with noncardiac surgery alone. The guidelines state that “coronary revascularization before noncardiac surgery is appropriate for only a small subset of patients . . . at very high risk.”1 Accordingly, we used this strategy, with dubious success, in four very-high-risk patients whom we excluded from randomization. The very low (3.4 percent) incidence of perioperative myocardial infarction and death from cardiac causes among patients given bisoprolol in our study makes myocardial revascularization even less attractive as a perioperative risk-reduction strategy.

Don Poldermans, M.D., Ph.D.
Eric Boersma, Ph.D.
Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands

Ian R. Thomson, M.D.
University of Manitoba, Winnipeg, MB R3T 2N2, Canada

2 References

1. 1

   Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 1996;27:910-948
   CrossRef | Web of Science | Medline

2. 2

   Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 1996;335:1713-1720[Erratum, N Engl J Med 1997;336:1039.]
   Full Text | Web of Science | Medline

Author/Editor Response

Litwack et al. have misinterpreted the message of my editorial, while defending screening practices that have no support from prospective evaluation studies. To correct their misrepresentation of my editorial, I must emphasize that I stated that the extraordinary reduction in risk needed to be confirmed by future research. More important, I did not recommend against the use of noninvasive testing in preoperative evaluation. I suggested that the study raises the possibility that “the role of noninvasive testing for ischemia may also be reduced in the future.”

This possibility flows logically from a randomized trial that found a 30-day mortality rate of 3.4 percent among high-risk patients undergoing vascular surgery, but I would be the first to agree that more research and considerable discussion must occur before the approach is incorporated into guidelines. Nevertheless, the results of this randomized trial stand in stark contrast to the complete absence of prospective, controlled data supporting current strategies for the use of noninvasive tests and revascularization. Ironically, the very guidelines1 cited by Litwack et al. explicitly acknowledge the absence of such data.

Given the magnitude of risk reduction with the use of beta-blockers that was demonstrated early in the study, continuation of the study to increase the sample size would have been unethical. As important as I believe the study by Poldermans et al. to be, I agree with Litwack and colleagues that it does not define the optimal management strategy for intermediate-risk and high-risk patients. What we need now are investigations that compare strategies that involve noninvasive tests for ischemia with medical management that includes the use of beta-blockers in these populations. If such investigations are performed, the next generation of guidelines will be based on data, not just opinion.

Thomas H. Lee, M.D.
Partners Community HealthCare, Boston, MA 02199

1 References

1. 1

   Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for peri-operative cardiovascular evaluation for noncardiac surgery: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Perioperative Cardiovascu-lar Evaluation for Noncardiac Surgery). J Am Coll Cardiol 1996;27:910-948
   CrossRef | Web of Science | Medline