Correspondence
Transfusion in Elderly Patients with Myocardial Infarction
N Engl J Med 2002; 346:779-782March 7, 2002
- Article
To the Editor:
Wu et al. report on the benefits of blood transfusion in elderly patients with acute myocardial infarction and anemia (Oct. 25 issue).1 Their data show that among patients with hematocrit values higher than 36.0 percent, those who received blood transfusions had a higher risk of death within 30 days than those who did not receive transfusions. The authors suggest that among older patients with acute myocardial infarction and anemia, transfusions benefit those with hematocrit values of 30.0 percent or lower. A corollary is that transfusion should be avoided in those with hematocrit values above 30.0 percent who do not have active bleeding, since in such patients, transfusion is associated with a significant increase in mortality. Transfusion of red cells in patients with hematocrit values exceeding 36.0 percent may not contribute much to oxygen-carrying capacity and may actually have negative effects on perfusion and oxygen delivery in the microvasculature because of alterations in red-cell membranes in stored blood and increased viscosity caused by the transfusion of red cells.
1 ReferencesMichael S. Albert, M.D.
Mercy Hospital of Buffalo, Buffalo, NY 14220
malbert3258@adelphia.net 1
Wu W-C ,Rathore SS ,Wang Y ,Radford MJ ,Krumholz MA . Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 2001;345:1230-1236
Full Text | Web of Science | Medline
To the Editor:
Wu et al. conclude that transfusions may improve the outcome in patients with acute myocardial infarction. In their retrospective study, the analysis was not controlled for normovolemia. The data in Table 1 of their report suggest that hypovolemia (a lower blood pressure and a higher heart rate on admission) influenced the outcome in the groups of patients with more severe anemia. Transfusions may have replaced needed volume when the administration of fluids would have sufficed. Controlling for normovolemia, Hébert et al.1 found that a restrictive transfusion policy (target hemoglobin level, 7 to 9 g per deciliter) did not worsen mortality or morbidity in patients in the intensive care unit, including those with ischemic heart disease, whereas a liberal transfusion policy (target hemoglobin level, 10 to 12 g per deciliter) worsened morbidity (as determined by changes in scores for multiple organ dysfunction).
Did significant differences in coexisting conditions result in a bias against transfusion in the group of patients with the most severe anemia (hematocrit, 5.0 to 24.0 percent), resulting in a statistically worse outcome in this group? Table 2 of the article shows that 28.7 percent of the patients in this group received no transfusions; 33.2 percent died in the hospital. On the basis of data in Table 2, we performed a simple analysis of the correlation between blood transfusion and mortality at 30 days and found a strong positive association (r=0.87, P=0.04). Table 3 of the article shows that the two groups of patients with hematocrit values that exceeded 36.0 percent had a higher mortality rate at 30 days if they underwent transfusion than if they did not (odds ratio, 1.43 and 1.66). This negative association was attributed to “other events,” rather than to transfusion. Prospective studies2 have shown that higher hematocrit values after coronary-artery bypass grafting are associated with worse outcomes (myocardial infarction and death).
2 ReferencesSeth Perelman, M.D.
David Moskowitz, M.D.
Henry Bennett, Ph.D.
Englewood Hospital and Medical Center, Englewood, NJ 07631
henry.bennett@ehmc. com 1
Hebert PC ,Yetisir E ,Martin C , et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular disease? Crit Care Med 2001;29:227-234
CrossRef | Web of Science | Medline2
Spiess BD ,Ley C ,Body SC , et al. Hematocrit value on intensive care unit entry influences the frequency of Q-wave myocardial infarction after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1998;116:460-467
CrossRef | Web of Science | Medline
To the Editor:
In their editorial on anemia, transfusion, and mortality,1 Drs. Goodnough and Bach conclude, “On the basis of the evidence presented by Wu et al., we recommend that hematocrit levels should be maintained above 33 percent in patients who present with acute myocardial infarction.” This conclusion is incorrect, inasmuch as it extends the interesting, albeit debatable, findings of Wu et al. to patients under the age of 65, a population that was not included in their data review.
I agree with Goodnough and Bach that clinical evidence to support transfusion guidelines is insufficient. Very few randomized studies have been published in this area of medicine, and most recommendations are guided by consensus rather than by science. Now that we have a study (even if it remains open to discussion) on the benefits of transfusions in elderly patients with acute myocardial infarction, we must resist the temptation to extend the authors' conclusions improperly. On the contrary, we now have to conduct similar (or better) studies in all the other populations of patients who are likely to benefit from erythrocyte transfusions.
1 ReferencesJean-François Hardy, M.D.
University of Montreal, Montreal, QC H3C 3J7, Canada
jean-francois.hardy@umontreal. ca 1
Goodnough LT ,Bach RG . Anemia, transfusion, and mortality. N Engl J Med 2001;345:1272-1274
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Albert interprets our data as suggesting that “transfusion should be avoided in those with hematocrit values above 30.0 percent . . . since in such patients, transfusion is associated with a significant increase in mortality.” This statement is incorrect. We found that transfusions were associated with a reduction in 30-day mortality among patients with hematocrit levels of up to 33.0 percent in our main analysis and in six of seven subgroup analyses; transfusion had a neutral effect on survival only when patients who died within 2 days after admission were excluded from the analysis. Thus, our data suggest that there may be a benefit (and there is certainly no harm) in providing transfusions to elderly patients with myocardial infarction and hematocrit levels up to 33.0 percent. In addition, we found that transfusion had a neutral effect on 30-day mortality among patients with hematocrit levels of 33.1 to 36.0 percent. Transfusion was associated with an increased risk of death within 30 days only among patients with hematocrit levels that exceeded 36.0 percent, not among those with values exceeding 30.0 percent, as Albert contends. We are uncertain about the mechanism of this increased risk of death. Although Albert notes possible decrements in perfusion and oxygen delivery due to the transfusion of red cells, the infrequent use of transfusion in this cohort (1.9 percent of patients with hematocrit levels exceeding 36.0 percent received transfusions) leads us to suspect the influence of unmeasured events that occurred later in the hospital stay.
Perelman and colleagues suggest that the benefit of transfusion in our cohort is due to volume replacement. Furthermore, they interpret data reported by Hébert and colleagues1 as suggesting that transfusion does not improve outcomes when used restrictively in patients in the intensive care unit who have cardiovascular disease. Although the restoration of volume in elderly patients with anemia may be of benefit, our multivariable analysis accounted for the possible effects of hypovolemia by adjusting for the mean arterial pressure and heart rate. This analysis suggests a survival benefit in addition to the restoration of volume, possibly by means of an improvement in the delivery of oxygen through stenosed coronary arteries or ischemic tissue because of elevated hemoglobin levels.2
In addition, Perelman and colleagues misrepresent the data reported by Hébert et al. They reported a consistent trend toward higher mortality rates (4.0 percent or higher) up to 60 days after admission among patients with ischemic heart disease who were treated according to the restrictive transfusion strategy. Their findings were not statistically significant because the analysis (with a total of 257 patients) had power to detect only a 17.0 percent absolute difference in mortality rates. Recognizing this trend, Hébert et al. reported that a restrictive transfusion strategy appears to be safe in critically ill patients with cardiovascular disease, “with the possible exception of patients with acute myocardial infarcts and unstable angina.”1
Randomized, controlled trials are needed to determine definitively the appropriate transfusion thresholds for elderly patients hospitalized with anemia and myocardial infarction. In the absence of these data, well-designed and carefully analyzed observational studies can provide important insights into the clinical care of this population of patients.
2 ReferencesSaif S. Rathore, M.P.H.
Yale University School of Medicine, New Haven, CT 06520-8025Wen-Chih Wu, M.D.
Brown University Medical School, Providence, RI 02912Harlan M. Krumholz, M.D.
Yale University School of Medicine, New Haven, CT 06520-80251
Hebert PC ,Yetisir E ,Martin C , et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Crit Care Med 2001;29:227-234
CrossRef | Web of Science | Medline2
Hebert PC ,Hu LQ ,Biro GP . Review of physiologic mechanisms in response to anemia. CMAJ 1997;156:Suppl 11:S27-S40
Web of Science
Author/Editor Response
The editorialists reply:
To the Editor: Dr. Hardy raises an important issue regarding the generalizability of our recommendation — based on the report by Wu et al.1 of findings in Medicare patients 65 years of age or older — to maintain hematocrit levels above 33 percent in patients hospitalized with myocardial infarction. Since the mean age of patients admitted to hospitals in the United States in 1999 with a primary diagnosis of myocardial infarction was 68 years,2 the results are relevant to the majority of patients, although a substantial minority may be younger than 65 years of age. We commented in our editorial that “the generalizability of the findings to younger patients . . . remains an open question.” But in the absence of any data to the contrary, the question is really whether we can assume that a more conservative approach to transfusion will result in optimal outcomes for younger patients or others with myocardial infarction whose demographic characteristics do not match those of the population included in the Cooperative Cardiovascular Project.
We believe that, in aggregate, the data support the hypothesis that a more liberal threshold for blood transfusion benefits patients with myocardial infarction regardless of their age group. Two large observational studies noted an association between a hemoglobin level below 9.5 to 10.0 g per deciliter and increased mortality among patients with cardiovascular disease and suggested that such patients do not tolerate anemia as well as patients with other conditions.3,4 Hébert et al.4 observed that when the hemoglobin level was less than 9.5 g per deciliter, red-cell transfusion led to a 40 percent decrease in mortality among severely ill patients with cardiovascular disease. In addition, in a recent prospective, randomized trial, within the subgroup of patients who also had ischemic heart disease, patients assigned to a restrictive approach to transfusion (with a target hemoglobin level of 7 to 9 g per deciliter) had a 30-day mortality rate that was 5 percent higher than that among patients assigned to a liberal approach to transfusion (with a target hemoglobin level of 10 to 12 g per deciliter) (P=0.38).5
Obviously, the risk of death for patients with myocardial infarction involves additional factors that are independent of age. Younger patients with large and complicated infarctions may also have limited reserve and heightened vulnerability to anemia. We believe it to be most prudent not to assume that anemia and transfusions affect the outcomes in patients with myocardial infarction differently depending solely on whether they are 65 or more years of age or are younger. Furthermore, we believe it is consistent with the best evidence that is currently available to recommend maintaining the hematocrit at 33 percent or higher in patients admitted to the hospital with acute myocardial infarction, regardless of their age.
5 ReferencesRichard G. Bach, M.D.
Lawrence T. Goodnough, M.D.
Washington University School of Medicine, St. Louis, MO 63110
goodnough@labmed.wustl. edu 1
Wu W-C ,Rathore SS ,Wang Y ,Radford MJ ,Krumholz HM . Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 2001;345:1230-1236
Full Text | Web of Science | Medline2
Rogers WJ ,Canto JG ,Lambrew CT , et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the U.S. from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2, and 3. J Am Coll Cardiol 2000;36:2056-2063
CrossRef | Web of Science | Medline3
Carson JL ,Duff A ,Poses RM , et al. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet 1996;348:1055-1060
CrossRef | Web of Science | Medline4
Hebert PC ,Wells G ,Tweeddale M , et al. Does transfusion practice affect mortality in critically ill patients? Am J Respir Crit Care Med 1997;155:1618-1623
Web of Science | Medline5
Hebert PC ,Yetisir E ,Martin C , et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Crit Care Med 2001;29:227-234
CrossRef | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Mehdi H. Shishehbor, Surabhi Madhwal, Vivek Rajagopal, Amy Hsu, Peter Kelly, Hitinder S. Gurm, Samir R. Kapadia, Michael S. Lauer, Eric J. Topol. (2009) Impact of Blood Transfusion on Short- and Long-Term Mortality in Patients With ST-Segment Elevation Myocardial Infarction. JACC: Cardiovascular Interventions 2:1, 46-53
CrossRef2
M. Marije Vis, Krischan D. Sjauw, René J. van der Schaaf, Karel T. Koch, Jan Baan, Jan G.P. Tijssen, Jan J. Piek, Robbert J. de Winter, José P.S. Henriques. (2007) Prognostic Value of Admission Hemoglobin Levels in ST-Segment Elevation Myocardial Infarction Patients Presenting With Cardiogenic Shock. The American Journal of Cardiology 99:9, 1201-1202
CrossRef
