Correspondence
Rescue Angioplasty after Thrombolysis
N Engl J Med 2006; 354:1639-1641April 13, 2006
- Article
To the Editor:
Gershlick et al. (Dec. 29 issue)1 report that emergency percutaneous coronary intervention (rescue PCI) for failed thrombolysis results in a statistically significant reduction in major cardiac and cerebrovascular events as compared with conservative treatment. In fact, there was a significant reduction only in the rate of myocardial infarction, and this result was based on very few events (12 in the conservative-treatment group and 3 in the PCI group). Even this finding may be spurious, since there are features of the trial design that may have led to bias. The use of intravenous heparin in the conservative-treatment group (for the 60 percent of patients who had received streptokinase) is not standard, has no evidence base, and may result in an increased risk of cerebral hemorrhage.2
The trial raises other questions. Were there differences in the use of medication for secondary prophylaxis (e.g., antiplatelet agents) at the time of discharge? Also, patients randomly assigned to the “new treatment” may have been more highly motivated to adopt lifestyle changes (e.g., discontinuing smoking or losing weight) than patients randomly assigned to conservative treatment. Were there any such differences?
2 ReferencesAndrew Owen, Ph.D., F.R.C.P.
Kent and Canterbury Hospital, Canterbury, Kent CT1 3NG, United Kingdom1
Gershlick AH ,Stephens-Lloyd A ,Hughes S , et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med 2005;353:2758-2768
Full Text | Web of Science | Medline2
Ridker PM ,Hebert PR ,Fuster V ,Hennekens CH . Are both aspirin and heparin justified as adjuncts to thrombolytic therapy for acute myocardial infarction? Lancet 1993;341:1574-1577
CrossRef | Web of Science | Medline
To the Editor:
We have several concerns regarding the recent report of the results of the Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis (REACT) trial. First, data on discharge medications are not reported. Was the use of statins and beta-blockers similar among the three groups? Second, mortality in the patients assigned to rescue PCI was 6.2 percent at six months, representing a 50 percent relative risk reduction. This reduction in mortality is greater than that seen in trials comparing primary PCI with thrombolysis.1 The patients assigned to rescue PCI had a mortality rate similar to that of patients undergoing primary PCI.2 These observations suggest that the mortality rate in the group receiving rescue PCI was unusually low. Third, no data on the revascularization strategy are presented. Was revascularization limited to the infarct-related artery, or were all high-grade stenoses treated? Finally, the authors do not provide any guidance about whether all patients in whom thrombolysis fails or only high-risk patients (and which ones) should be treated. This is of particular concern, since difficulty in the recruitment of patients may have resulted in selection bias, with the preferential enrollment of high-risk patients.
2 ReferencesShahid Aziz, M.D.
David Ramsdale, M.D.
Cardiothoracic Centre, Liverpool L14 3PE, United Kingdom
saziz1@btinternet.com 1
Keeley EC ,Boura JA ,Grines CL . Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20
CrossRef | Web of Science | Medline2
Grines C ,Patel A ,Zijlstra F ,Weaver WD ,Granger C ,Simes RJ . Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials. Am Heart J 2003;145:47-57
CrossRef | Web of Science | Medline
To the Editor:
The study by Gershlick et al. provides corroboration of data that are already known and available.1,2 The study was small and, as a result, unable to detect any difference in rates of death or heart failure.
It would be important to know the reasons for the low use of stents (68.5 percent) and the glycoprotein IIb/IIIa receptor inhibitor abciximab (43.4 percent) in the present study. The use of both these strategies (stenting and abciximab) is recommended in rescue PCI,3 and some data show benefits from the use of abciximab.4
Patients undergoing rescue PCI present two challenging issues — platelet activation induced by the thrombolytic agent and bleeding at the access site after removal of the arterial sheath. We have used a strategy that includes intracoronary administration of abciximab to achieve rapid, local platelet inhibition before stenting the culprit lesion and the use of the Angioseal closure device to prevent local arterial bleeding at the access site, and we have had success in a small series of 15 patients (unpublished data).
4 ReferencesSanjiv Sharma, M.D.
Brijesh Bhambi, M.D.
William Nyitray, M.D.
Bakersfield Heart Hospital, Bakersfield, CA 93301
sanjiv1122@yahoo.com 1
Ellis SG ,da Silva ER ,Heyndrickx G , et al. Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction. Circulation 1994;90:2280-2284
Web of Science | Medline2
Belenkie I ,Traboulsi M ,Hall CA , et al. Rescue angioplasty during myocardial infarction has a beneficial effect on mortality: a tenable hypothesis. Can J Cardiol 1992;8:357-362
Web of Science | Medline3
Lansky AJ, Stone GW. Percutaneous intervention for acute coronary syndromes. In: Safian RD, Freed MS, eds. The manual of interventional cardiology. 3rd ed. Royal Oak, Mich.: Physicians' Press, 2001:94.
4
Miller J ,Ohman E . Survival benefit of abciximab during early rescue angioplasty: analysis of 387 patients from the GUSTO-III trial. J Am Coll Cardiol 1998;31:Suppl A:191A-191A
CrossRef | Web of Science
To the Editor:
The article by Gershlick et al. regarding the benefit of rescue PCI raises some specific issues. First, the authors included patients older than 75 years of age. Thrombolytic therapy is associated with an increased rate of bleeding complications in this age group,1 which might have influenced some of the outcomes. Second, a total of 7.9 percent of the study subjects had had previous revascularization procedures. Among patients in whom a stent had been implanted within the past six weeks, the role of fibrinolytic agents is questionable. Third, anticoagulation plays a vital role in the success of fibrinolysis, but the duration, initial dose, and maintenance levels of anticoagulation therapy were not reported. Fourth, the additional delay in time to treatment with PCI might have been longer if more patients had been recruited from hospitals without interventional capabilities.
Finally, cardiologists who may be keen to adopt an early interventional strategy in the setting of failed thrombolysis would like to know the implications on resources, including staffing issues, especially among patients presenting after 5 p.m. and on weekends. Do the authors have cost data?
1 ReferencesGirish N. Viswanathan, M.D.
Glan Clywd Hospital, Rhyl LL18 5UJ, United Kingdom
girishviswa@gmail.com Sennimalai Sankar, M.R.C.P.
Wrexham Maelor Hospital, Wrexham LL13 7TZ, United Kingdom1
Dieker HJ ,Brouwer MA ,Verheugt FW . ESC guidelines for percutaneous coronary interventions. Eur Heart J 2005;26:2475-2475
CrossRef | Web of Science | Medline
Author/Editor Response
The composite primary end point in the REACT trial is standard for randomized trials in this field and avoided “softer” physician-directed end points, such as revascularization. Although the REACT trial was not powered for significant differences in individual outcomes, which should thus be interpreted cautiously, mortality in the rescue PCI group (6.2 percent) is in keeping with that of similar smaller studies and with the British Cardiovascular Intervention Society audit rate (in 750 patients) of 5.6 percent. Comparisons between the REACT trial and historical primary PCI meta-analyses are unwise, given differences in data collection and the accumulation of end points in the meta-analyses. We agree that the REACT trial extends the evidence base by corroborating smaller studies that had left uncertainty regarding rescue PCI.
Angiographic analysis is ongoing, but as reported, the rescue PCI strategy was aimed at the infarct-related artery. Whether the infarct-related artery only or all lesions of significance should be treated is unresolved even in primary PCI. Only 3.7 percent of patients had had previous PCI. The use of stents and glycoprotein IIb/IIIa inhibitors, which have increasingly become routine, was at the discretion of the investigators. Regarding the potential selection of high-risk patients in the REACT trial, we believe physician bias actually resulted in such patients' being treated with rescue PCI outside the trial.
We are aware that heparin is not standard treatment after streptokinase, as Owen points out. The REACT trial, however, was a trial of failed thrombolysis — patients randomly assigned to repeated thrombolysis received a fibrin-specific agent. Heparin was given at the time of the first thrombolytic agent according to local policy and without regard to the study, which commenced only after failed thrombolytic therapy. As reported, patients received heparin to maintain a standard partial-thromboplastin time ratio.
In response to Viswanathan and Sankar, concerns regarding the risk of excess bleeding in the elderly were managed by adopting blood-pressure and weight constraints in those older than 75 years of age, in accordance with previous data about elderly patients receiving thrombolytic agents. In a follow-up paper by the REACT trial investigators (in preparation), elderly patients had more end-point events overall but still benefited from rescue PCI. Analyses of bleeding against various factors are ongoing, but serious bleeding was rare in the group assigned to rescue PCI. The strategies of Sharma et al. to reduce bleeding are welcomed, although their study was nonrandomized and is as yet unpublished.
We agree that the implications on resources are paramount, and prospectively planned cost–benefit and quality-of-life analyses are under way. Further analyses are also under way regarding rehabilitation and medications at the time of discharge, although it is unlikely that lifestyle changes within six months would have a substantial effect on the hard reduction in end-point events that was seen.
Anthony H. Gershlick, M.B., B.S.
Amanda Stephens-Lloyd, R.N., M.Sc.
University Hospitals of Leicester, Leicester LE3 9QP, United Kingdom
agershlick@aol.com Robert Wilcox, M.D.
Queens Medical Center, Nottingham NG7WUH, United Kingdom
