Correspondence
Persistent Coronary Occlusion after Myocardial Infarction
N Engl J Med 2007; 356:1681-1684April 19, 2007
- Article
To the Editor:
The Occluded Artery Trial (OAT), reported by Hochman et al. (Dec. 7 issue),1 compared percutaneous coronary intervention (PCI) with stent placement and optimal medical therapy with optimal medical therapy alone in patients who had persistent coronary occlusion after myocardial infarction. This report and the group's earlier report on the trial design2 indicate that the study was designed to have 90% power to detect a 25% reduction in the rate of the primary end-point event — a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure — in patients undergoing PCI, assuming a 3-year event rate of 25% with medical therapy. The number of observed events required to meet these characteristics is nearly 508. The report includes only 301 study events (approximately 60% of the expected rate), suggesting that the report was published well before full information was available.
A data and safety monitoring board oversaw the conduct of the trial and performed interim monitoring. The study may have been published before full information was available because the board recognized that a futility analysis showed that the estimated hazard ratio in the PCI group (1.16) was inconsistent with the alternative hypothesis (hazard ratio, 0.75) (P<0.001). Thus, it was nearly certain that the study would never show a benefit of PCI. If this is indeed what happened, it should have been disclosed in the report.
2 ReferencesJames R. Anderson, Ph.D.
University of Nebraska Medical Center, Omaha, NE 68198-4380
janderson@unmc.edu 1
Hochman JS ,Lamas GA ,Buller CE , et al. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med 2006;355:2395-2407
Full Text | Web of Science | Medline2
Hochman JS ,Lamas GA ,Knatterud GL , et al. Design and methodology of the Occluded Artery Trial (OAT). Am Heart J 2005;150:627-642
CrossRef | Web of Science | Medline
To the Editor:
In their study evaluating the open-artery hypothesis, Hochman et al. included patients with mild or moderate inducible ischemia in the infarct zone (237 patients). However, the outcome in this subgroup after PCI (125 patients) or medical therapy (112 patients) was not reported separately. On a physiological basis and from the standpoint of clinical practice, it is this subgroup that is most likely to benefit from successful PCI of the infarct-related artery. The guidelines of the American College of Cardiology and the American Heart Association1 recommend coronary angiography only in the presence of inducible ischemia or an ejection fraction of less than 40% in patients in stable condition who are not undergoing primary PCI for acute myocardial infarction. Some operators may currently be performing PCI in all patients with occluded infarct-related arteries on the basis of the open-artery hypothesis.2-4 However, most clinicians, including those in our group, tend to be more aggressive with late PCI in the setting of inducible ischemia. Therefore, until outcome data for this subgroup are available, labeling late PCI as ineffective in all cases of occluded infarct-related vessels is inappropriate, because late PCI may have a role in the treatment of selected patients.
4 ReferencesNagapradeep Nagajothi, M.D.
Jose-Luis E. Velazquez-Cecena, M.D.
Sandeep Khosla, M.D.
Rosalind Franklin University of Medicine and Sciences, North Chicago, IL 600641
Antman EM ,Anbe DT ,Armstrong PW , et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction -- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004;110:588-636[Erratum, Circulation 2005;111:2013.]
CrossRef | Medline2
Horie H ,Takahashi M ,Minai K , et al. Long-term beneficial effect of late reperfusion for acute anterior myocardial infarction with percutaneous transluminal coronary angioplasty. Circulation 1998;98:2377-2382
Web of Science | Medline3
Lange RA ,Cigarroa RG ,Wells PJ ,Kremers MS ,Hills LD . Influence of anterograde flow in the infarct artery on the incidence of late potentials after acute myocardial infarction. Am J Cardiol 1990;65:554-558
CrossRef | Web of Science | Medline4
Hillis LD ,Lange RA . Myocardial infarction and the open-artery hypothesis. N Engl J Med 2006;355:2475-2477
Full Text | Web of Science | Medline
To the Editor:
Hochman et al. found no clinical evidence to support the open-artery hypothesis. However, OAT failed to enroll the ideal patient in whom to test this hypothesis. In studies in animals,1 late reperfusion has been shown to limit the degree of infarct expansion in a nonsalvageable infarct zone. In sharp contrast, the majority of patients (>85%) in this trial had collateral vessels at baseline, a finding presumably responsible for the high prevalence of viability of the infarct zone (69% of patients in the viability substudy). Arguably, delayed recanalization of the infarct-related artery in this setting will lead to loss of previously recruited collateral flow,2 reexposing the once-protected distal vascular bed and viable myocardium to future upstream vascular events. The inclusion of patients without existing collateral vessels might have provided a more appropriate clinical model to test the late open-artery hypothesis. No analysis of the subgroup of patients without collateral vessels was reported, although such an analysis would be of great interest.
2 ReferencesBrian Wong, M.D.
Sudbury Regional Hospital, Sudbury, ON P3E 3B6, Canada1
Hochman JS ,Choo H . Limitation of myocardial infarct expansion by reperfusion independent of myocardial salvage. Circulation 1987;75:299-306
CrossRef | Web of Science | Medline2
Werner GS ,Emig U ,Mutschke O ,Schwartz G ,Bahrmann P ,Figulla HR . Regression of collateral function after recanalization of chronic total coronary occlusions: a serial assessment by intracoronary pressure and Doppler recordings. Circulation 2003;108:2877-2882
CrossRef | Web of Science | Medline
To the Editor:
Hochman et al. report that there was no significant difference in mortality between the PCI group and the medical-therapy group. Rates of mortality due to arrhythmia were not reported, although a substantial number of patients in each group might have died from ventricular arrhythmia. Nothing was said about the number of patients who received an implantatable cardioverter–defibrillator (ICD) or cardiac resynchronization therapy during follow-up. Both these interventions reduce the total mortality and mortality due to arrhythmia among survivors of myocardial infarction with ejection fractions of less than 35%.1,2 If there was a significant difference between the two study groups in rates of use of ICDs and cardiac resynchronization therapy, it might have affected the mortality rates and the result of the study. In contrast, a similar rate in the two groups might have obscured the potential benefit of restoring antegrade flow in the occluded infarct-related artery for reducing the risk of death from arrhythmia.
2 ReferencesOkan Erdogan, M.D.
Trakya University, 22030 Edirne, Turkey
okanerdogan@yahoo.com 1
Bristow MR ,Saxon LA ,Boehmer J , et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150
Full Text | Web of Science | Medline2
Bardy GH ,Lee KL ,Mark DB , et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237[Erratum, N Engl J Med 2005;352:2146.]
Full Text | Web of Science | Medline
To the Editor:
In the randomized trial reported by Hochman et al., PCI, as compared with optimal medical therapy, in patients with total occlusion of the infarct-related artery did not significantly reduce the rate of death, reinfarction, or NYHA class IV heart failure. Nevertheless, the study raises some concerns. First, the major benefit of elective PCI should be considered to be an improvement in the quality of life, not a reduction in cardiovascular events, especially in patients at low risk.1,2 Unfortunately, the long-term effect of PCI on the quality of life according to disease-specific measures of health status was not reported, with the exception of the recurrence of angina, which was significantly reduced in the PCI group at 2 years. Second, the patients enrolled in the study did not seem to be at high risk: they were relatively young and had a relatively small area of myocardium at risk, well-developed collateral circulation, and preserved left ventricular ejection fraction. Therefore, a possible benefit of PCI in improving the quality of life cannot be ruled out.
2 ReferencesLeonardo De Luca, M.D.
Fabrizio Tomai, M.D.
European Hospital, 00149 Rome, Italy
leo.deluca@libero. it 1
Curtis JP ,Krumholz HM . Keeping the patient in view: defining the appropriateness of percutaneous coronary interventions. Circulation 2004;110:3746-3748
CrossRef | Web of Science | Medline2
Weintraub WS ,Sadanandan S . Percutaneous coronary intervention in stable patients after acute myocardial infarction. Circulation 2003;108:1292-1294
CrossRef | Web of Science | Medline
To the Editor:
In their editorial accompanying the report on OAT, Hillis and Lange suggest that the use of beta-blockers in the study may have obscured the benefits of restoring antegrade flow after myocardial infarction, and that all survivors of myocardial infarction should receive a beta-blocker indefinitely. Although beta-blockade has been shown to be beneficial in high-risk patients, such as those with heart failure, ischemic symptoms, arrhythmias, or persistent occlusion, the benefit of long-term beta-blocker therapy in an unselected population of patients after myocardial infarction is less clear.1 The majority of trials of long-term beta-blocker therapy after myocardial infarction were conducted in the era before routine use of aspirin, statins, thrombolysis, and angiotensin-converting–enzyme inhibitors; did not include large numbers of patients; and showed a long-term mortality benefit only when the results of individual trials were pooled.2,3 Although long-term use of beta-blockers after myocardial infarction is strongly encouraged in current guidelines and is commonly practiced, the true benefit of beta-blockers with current medical therapy in an unselected patient population remains unclear.
3 ReferencesDoson Chua, Pharm.D.
St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada
dchua@providencehealth.bc. ca Anita Lo, Pharm.D.
Ridge Meadows Hospital, Maple Ridge, BC V2X 7G5, CanadaI. Fan Kuo, B.Sc. (Pharm), B.Sc. (Pharm)
St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada1
Antman EM ,Anbe DT ,Armstrong PW , et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). J Am Coll Cardiol 2004;44:E1-E211
CrossRef | Medline2
Freemantle N ,Cleland J ,Young P ,Mason J ,Harrison J . Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999;318:1730-1737
CrossRef | Web of Science | Medline3
Freemantle N ,Urdahl H ,Eastaugh J ,Hobbs FD . What is the place of beta-blockade in patients who have experienced a myocardial infarction with preserved left ventricular function? Evidence and (mis)interpretation. Prog Cardiovasc Dis 2002;44:243-250
CrossRef | Web of Science | Medline
Author/Editor Response
De Luca and Tomai ask about the quality of life of patients in OAT. We found only a transient reduction in angina with PCI; by 3 years, there was no significant difference between the PCI group and the medical therapy group in the prevalence of angina (9.1% and 10.3%, respectively; P=0.53). Moreover, PCI is appropriately used for the treatment of angina refractory to optimal medical therapy. Data on quality of life and economic data were collected for a subgroup of patients but have not yet been reported. There was no suggestion that PCI reduced the rates of death, myocardial infarction, or heart failure in subgroups with indicators of high risk (e.g., anterior infarct and low ejection fraction).
With regard to Anderson's concerns, our study was not an event-driven trial, and the data and safety monitoring board did not stop the trial because of futility. The observed rate of heart failure was lower than projected, accounting for the lower-than-expected number of events. The trial did, however, achieve 81% power to detect the targeted relative risk reduction at an alpha level of 0.05 and the observed event rates.
Erdogan brings up a valid point about the potential for confounding on the basis of the patients' status with respect to ICD and cardiac resynchronization therapy. In the PCI group, 2.4% of the patients received an ICD, and in the medical therapy group, 1.8% received an ICD — a difference that was not significant. Data on cardiac resynchronization therapy were not collected; however, most cardiac resynchronization devices have the function of an ICD, which would have been captured in our ICD data. It is unlikely that the rate of cardiac resynchronization therapy would have differed significantly between the two randomized study groups, since there were similar event rates over time for all measures of heart failure.
The comments of Nagajothi and colleagues provide an interesting contrast to the comments of Wong. Nagajothi and colleagues suggest that PCI may be more beneficial in patients with inducible ischemia, and Wong suggests that PCI may be beneficial only when there is no viability in the infarct zone. There was no interaction between either the presence of collaterals or ischemia on stress testing and the treatment effect in our trial.
In their editorial, Hillis and Lange note that they have shown an association between beta-blockers and improved survival among patients with persistent occlusion of the infarct-related artery1,2 and suggest that PCI might have had an effect on events in patients in OAT who were not receiving beta-blockers. A total of 263 patients in the trial were not given beta-blockers at discharge, whereas 1886 patients were. The primary end point did not differ significantly according to the study treatment in either of these two subgroups. The cumulative 4-year event rate for the death, reinfarction, and class IV heart failure was 17.0% in the PCI group and 17.9% in the medical therapy group among patients who were not given beta-blockers at discharge and 16.2% and 14.9%, respectively, among those who were given beta-blockers at discharge. There was no interaction between treatment and the prescription of beta-blockers at discharge for the primary end point (P=0.40).
2 ReferencesJudith S. Hochman, M.D.
New York University School of Medicine, New York, NY 10016Sandra Forman, M.A.
Maryland Medical Research Institute, Baltimore, MD 21210Harmony R. Reynolds, M.D.
New York University School of Medicine, New York, NY 10016for the Occluded Artery Trial Investigators
1
Cigarroa RG ,Lange RA ,Hillis LD . Prognosis after acute myocardial infarction in patients with and without residual anterograde coronary blood flow. Am J Cardiol 1989;64:155-160
CrossRef | Web of Science | Medline2
Glamann DB ,Lange RA ,Hillis LD . Beneficial effect of long-term beta blockade after acute myocardial infarction in patients without anterograde flow in the infarct artery. Am J Cardiol 1991;68:150-154
CrossRef | Web of Science | Medline
Author/Editor Response
Several placebo-controlled trials, encompassing data from more than 35,000 survivors of acute myocardial infarction who did not receive reperfusion therapy, have shown that long-term therapy with beta-adrenergic blockers (propranolol,1 timolol,2 and metoprolol3) reduces long-term mortality. As noted by Chua et al., this salutary effect is greatest in so-called high-risk patients — those of advanced age or with evidence of large infarction, anterior infarction, complex ventricular ectopy, or hemodynamic evidence of left ventricular systolic dysfunction. Even for survivors of myocardial infarction who are not at high risk, however, long-term beta-blocker therapy is recommended, unless, of course, a contraindication is present.4
4 ReferencesL. David Hillis, M.D.
University of Texas Southwestern Medical Center, Dallas, TX 75390Richard A. Lange, M.D.
Johns Hopkins Medical Institutions, Baltimore, MD 212871
Beta-Blocker Heart Attack Study Group
CrossRef | Web of Science2
The Norwegian Multicenter Study Group
Full Text | Web of Science | Medline3
Hjalmarson A ,Elmfeldt D ,Herlitz J , et al. Effect on mortality of metoprolol in acute myocardial infarction: a double-blind randomised trial. Lancet 1981;2:823-827
CrossRef | Web of Science | Medline4
Ryan TJ ,Anderson JL ,Antman EM , et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1996;28:1328-1428
CrossRef | Web of Science | Medline
- Citing Articles (3)
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1
John K. French, Jennifer A. Shearer. (2009) Are we letting good stories obscure the truth—Can qualitative techniques provide clarification?. American Heart Journal 157:4, 597-598
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George C.M. Siontis, Athina Tatsioni, Demosthenes G. Katritsis, John P.A. Ioannidis. (2009) Persistent reservations against contradicted percutaneous coronary intervention indications: Citation content analysis. American Heart Journal 157:4, 695-701
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Sammy Elmariah, Sidney C Smith, Valentin Fuster. (2008) Late medical versus interventional therapy for stable ST-segment elevation myocardial infarction. Nature Clinical Practice Cardiovascular Medicine 5:1, 42-52
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