Correspondence
Off-Pump Coronary Bypass Surgery
N Engl J Med 2003; 348:1928-1931May 8, 2003
- Article
To the Editor:
We welcome the article by Nathoe and colleagues (Jan. 30 issue).1 In its infancy, off-pump coronary-artery bypass was mostly used in high-risk patients,2 with observed reductions in morbidity and mortality.3 Cardiopulmonary bypass has two main disadvantages: a systemic inflammatory response syndrome and microembolization, which leads to multiorgan dysfunction.4 It seems rational that all patients, both those at high risk and those at low risk, would benefit from a technique that avoids the use of cardiopulmonary bypass. The study by Nathoe et al. did not show a significant difference in cardiac outcomes between coronary-artery bypass grafting with cardiopulmonary bypass and off-pump coronary-artery bypass in low-risk patients. Coronary-artery bypass grafting was 14.1 percent more expensive at one year. A similar article, by Abu-Omar and Taggart,4 adds to the strong evidence that low-risk populations are the best candidates for off-pump coronary-artery bypass. Those authors rightly highlight two randomized trials, both of which showed reductions in postoperative morbidity and the length of the hospital stay in low-risk patients who underwent off-pump coronary-artery bypass. These articles are refreshing because they remind cardiologists and cardiac surgeons that off-pump coronary-artery bypass is beneficial in both high-risk and low-risk patients and that it is more cost-effective in low-risk patients.
4 ReferencesHarry W. Donias, M.D.
Ravi Pande, M.D.
Hratch L. Karamanoukian, M.D.
Center for Less Invasive Cardiac Surgery and Robotic Heart Surgery, Buffalo, NY 14203
drk@diagnosisheart.com 1
Nathoe HM ,van Dijk D ,Jansen EWL , et al. A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients. N Engl J Med 2003;348:394-402
Full Text | Web of Science | Medline2
D'Ancona G ,Karamanoukian HL ,Soltoski P ,Salerno TA ,Bergsland J . Changing referral pattern in off-pump coronary artery bypass surgery: a strategy for improving surgical results. Heart Surg Forum 1999;2:246-249
Medline3
Cleveland JC Jr ,Shroyer AL ,Chen AY ,Peterson E ,Grover FL . Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity. Ann Thorac Surg 2001;72:1282-1289
CrossRef | Web of Science | Medline4
Abu-Omar Y ,Taggart DP . Off-pump coronary artery bypass grafting. Lancet 2002;360:327-330
CrossRef | Web of Science | Medline
To the Editor:
Rose provides an insightful Perspective1 on the study by Nathoe et al., who compared off-pump and on-pump coronary bypass surgery. That study was designed to prove the superiority of one strategy over the other according to an intention-to-treat analysis of 281 patients; it was not designed to prove either the equivalence or the noninferiority of either surgical approach to the other. We take issue with Dr. Rose's conclusion about the “equivalence” of the techniques with respect to any of the end points. Superiority is proven when the data refute the equivalence of the two treatments (the null hypothesis) and support the alternative hypothesis that one is better. Proof of equivalence requires special consideration in trial design to prove with statistical confidence that the outcome of two or more strategies does not differ beyond a predefined range (delta) in both the positive and the negative direction (a two-sided test).2,3 The difference between lack of proof of superiority and equivalence is important, and absence of evidence of a difference is not the same as evidence of an absence of difference.4,5
5 ReferencesMardi Gomberg-Maitland, M.D.
Jonathan L. Halperin, M.D.
Mount Sinai Medical Center, New York, NY 10469
mardi.gomberg@msnyuhealth. org 1
Rose EA . Off-pump coronary-artery bypass surgery. N Engl J Med 2003;348:379-380
Full Text | Web of Science | Medline2
Jones B ,Jarvis P ,Lewis JA ,Ebbutt AF . Trials to assess equivalence: the importance of rigorous methods. BMJ 1996;313:36-39[Erratum, BMJ 1996;313:550.]
CrossRef | Web of Science | Medline3
Siegel JP . Equivalence and noninferiority trials. Am Heart J 2000;139:S166-S170
CrossRef | Web of Science | Medline4
Fleming TR . Design and interpretation of equivalence trials. Am Heart J 2000;139:S171-S176
CrossRef | Web of Science | Medline5
White HD . Thrombolytic therapy and equivalence trials. J Am Coll Cardiol 1998;31:494-496
CrossRef | Web of Science | Medline
To the Editor:
Nathoe et al. conclude that off-pump coronary bypass surgery is cost effective as compared with on-pump surgery. However, their graphic presentation of the data is inappropriate, leading to an incorrect conclusion.
The convention for displaying a cost-effectiveness plane is to position the standard intervention at the origin and to plot the new intervention relative to that reference. The probability of cost effectiveness is then determined as the proportion of points lying below the threshold value.1 In this study, on-pump surgery is the standard and should be considered the reference. When it is, most of the bootstrap estimates are located in the southwest quadrant (Figure 1Figure 1
Estimate of the Joint Density Function for Incremental Costs and Effects (Assuming Joint Normality of Cost and Effect Differences), Covering 5, 50, and 95 Percent of the Integrated Joint Density.), where the threshold was $40,000, not $20,000, per quality-adjusted year of life — a reflection of society's reluctance to forgo an accepted therapy for a less expensive, less effective option.3 In this case, the probability that the off-pump technique is cost effective is considerably less than 95 percent.Contrary to the authors' suggestion, our previous work does not prescribe a consensus threshold value3 but does endorse flexible reporting of cost effectiveness, with the use of acceptability curves — an approach recently used in the Journal.4
4 ReferencesJeff Healey, M.D.
Elisabeth Fenwick, Ph.D.
Bernie O'Brien, Ph.D.
McMaster University, Hamilton, ON L8L 2X2, Canada1
Briggs AH ,Fenn P . Confidence intervals or surfaces? Uncertainty on the cost-effectiveness plane. Health Econ 1998;7:723-740
CrossRef | Web of Science | Medline2
Briggs AH ,O'Brien BJ . The death of cost-minimization analysis? Health Econ 2001;10:179-184
CrossRef | Web of Science | Medline3
O'Brien BJ ,Gertsen K ,Willan AR ,Faulkner LA . Is there a kink in consumers' threshold value for cost-effectiveness in health care? Health Econ 2002;11:175-180
CrossRef | Web of Science | Medline4
Manns BJ ,Lee H ,Doig CJ ,Johnson D ,Donaldson C . An economic evaluation of activated protein C treatment for severe sepsis. N Engl J Med 2002;347:993-1000
Full Text | Web of Science | Medline
Author/Editor Response
In response to Healey and colleagues: What we found is that in comparison with on-pump surgery, off-pump surgery reduced the direct medical costs by $1,839 at one year (P<0.01) but was associated with only 0.01 less quality-adjusted year of life (95 percent confidence interval, –0.03 to 0.04; P=0.70).
We are aware of and respect the convention concerning cost-effectiveness analysis proposed by Healey and colleagues, and our original analysis was performed accordingly. Yet we decided to present the data the way we did for two reasons. First, whatever analysis was chosen, the results shifted only slightly. Second, the results may be difficult to interpret and may thus be confusing for a reader who is not an expert in this field, who might not see that a combination of negative costs and negative effects (quality-adjusted years of life) still results in a positive incremental cost-effectiveness ratio. This type of presentation was strongly requested by one of the reviewers. The original analysis, in which we used the methods proposed by Healey and colleagues, showed that 87 percent of the bootstrap estimates were below the defined threshold and thus indicated that off-pump surgery has a potential economic benefit. We therefore disagree with the statement by Healey et al. that the current presentation leads to an incorrect conclusion.
In accordance with the Dutch guidelines,1 we originally included indirect nonmedical costs associated with sick leave in the analysis as well. After off-pump surgery, the sick leave was 35.4 days, as opposed to 38.4 days after on-pump surgery. This suggests an additional cost benefit of $681 for off-pump surgery and would have placed 95 percent of the bootstrap estimates below the defined threshold. In our view, this is an important finding, which is not considered of primary interest according to other guidelines.2
We do not agree that we would be suggesting that $20,000 per quality-adjusted year of life gained might be considered a consensus of societal willingness to pay the threshold amount. We recognize that any figure in the absence of empirical data and a clinical context is arbitrary. Introducing acceptability curves as a way of presenting our results would not resolve the issue of arbitrary thresholds, nor would it add to the current interpretation of our data. In fact, we believe that by using the threshold values of $20,000 and $40,000 as ballpark figures, readers will be able to draw their own conclusions.
2 ReferencesHendrik M. Nathoe, M.D.
Erik Buskens, Ph.D.
Peter P.T. de Jaegere, Ph.D.
University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands
pjaegere@azu.nl 1
Oostenbrink JB, Koopmanschap MA, Rutten FFH. Handleiding voor kostenonderzoek, methoden en richtlijnprijzen voor economische evaluaties in de gezondheidszorg. Amstelveen, the Netherlands: College voor Zorgverzekeringen, 2000.
2
Weinstein MC ,Siegel JE ,Garber AM , et al. Productivity costs, time costs and health-related quality of life: a response to the Erasmus Group. Health Econ 1997;6:505-510
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Author/Editor Response
Drs. Gomberg-Maitland and Halperin raise important issues that deserve clarification. They are entirely correct in stating that the study by Nathoe et al., on which my Perspective was based, was not primarily designed to prove the equivalence of off-pump and on-pump bypass surgery. I take issue, however, with their statement that I had reached a “conclusion about the `equivalence' of the techniques with respect to any of the end points.”
Although I state in the Perspective that “Nathoe et al. . . . report the equivalence of off-pump and on-pump bypass surgery” with regard to multiple safety end points, I further note that “the safety implications of the data are not definitive, since the trial was underpowered to compare the two approaches with respect to mortality and complication rates.” When one is putting issues in perspective, describing a report is not the same as reaching a conclusion.
Eric A. Rose, M.D.
Columbia University College of Physicians and Surgeons, New York, NY 10021
ear3@columbia.edu
