European Heart Journal Advance Access originally published online on November 28, 2005
European Heart Journal 2006 27(2):246-247; doi:10.1093/eurheartj/ehi661
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Mechanisms of death in elderly patients with acute myocardial infarction exposed to fibrinolytic therapy: reply
Department of Cardiology
Hospital General Universitario
‘Gregorio Marañón’
Dr Esquerdo 46
Madrid 28007
Spain
Tel: +34 915 868 293
Fax: +34 915 868 276
E-mail address: hecbueno{at}jet.es
Department of Cardiology
Hospital General Universitario
‘Gregorio Marañón’
Madrid
Spain
Department of Cardiology
Hospital General Universitario
‘Gregorio Marañón’
Madrid
Spain
Department of Cardiology
Hospital General Universitario
‘Gregorio Marañón’
Madrid
Spain
We appreciate the comment of Poli
et al., regarding the high rate of free wall rupture (FWR) in older patients with acute myocardial infarction (AMI) treated with streptokinase. We agree that FWR is largely underdiagnosed. That is explained by the fact that the most frequent clinical presentation of FWR is sudden electromechanical dissociation, which usually leads to death in few minutes. Therefore, an experienced team with facilities and willingness to perform emergent echocardiographic studies at any time, even during resuscitation manoeuvres, is needed to have an accurate estimate of FWR incidence. Primary angioplasty is not associated with an increased risk of FWR. This and other advantages suggest that mechanical reperfusion is the preferred reperfusion strategy in the elderly, although this is currently under investigation. However, the benefits of primary angioplasty are limited by its reduced availability. When it is not available, two questions come up in clinical decision-making: should we use thrombolytic therapy to treat very old patients with AMI due to the associated risks? if yes, what is the best therapeutic regime for thrombolysis in these patients?
There are no definite answers for both questions. A substudy of the Fibrinolytic Therapy Trialists' meta-analysis found a large survival benefit at 30 days in eligible AMI patients >75 years old treated with lytics compared with those who received placebo.1 The risk of FWR seems to explain an early hazard that some but not all observational studies have found associated with thrombolysis in older patients, whereas most studies found a long-term survival benefit among them. Therefore, the best current knowledge suggests that, in spite of an early risk, thrombolytic therapy is beneficial and should be used in most elderly patients with AMI when there is no alternative treatment. Whether this benefit is constant across different subgroups such as women, patients with anterior infarcts, or those arriving after 6 h from symptom onset needs further research.
The best thrombolytic regimen to treat AMI in the oldest patients is not known. Our results2 as well as Polic's and others3 suggest that the rate of FWR after treatment with streptokinase is very high. A post hoc analysis of the Global Utilization of Strategies To open Occluded arteries (GUSTO) trial showed that up to the age of 85 years alteplase is associated with better results than streptokinase in terms of death or death plus disabling stroke with a higher risk of intracerebral haemorrhage.4 Later, a subgroup analysis of the Assessment of the Safety and Efficacy of a New Thrombolytic regimen (ASSENT)-2 trial showed that the only subgroup in which tenecteplase seemed to be better than alteplase was in women >75 years old.5 Additionally, the ASSENT-3 Plus trial revealed that the rate of intracerebral bleeding in patients >75 years old treated with tenecteplase plus enoxaparin is unacceptably high (6.7%), whereas the combination with unfractionated heparin does not increase cerebral bleeding.6 Although none of these data are direct evidence, we speculate that tenecteplase plus unfractionated heparin is the best pharmacological reperfusion therapy for the oldest patients with AMI.
References
- White HD. Thrombolytic therapy in the elderly. Lancet 2000;356:2028–2030.[CrossRef][ISI][Medline]
- Bueno H, Martínez-Sellés M, Pérez-David E, López-Palop R. Effect of thrombolytic therapy on the risk of cardiac rupture and mortality in older patients with first acute myocardial infarction. Eur Heart J 2005;26:1705–1711.
[Abstract/Free Full Text] - Maggioni AP, Maseri A, Fresco C, Franzosi MG, Mauri F, Santoro E, Tognoni G. Age-related increase in mortality among patients with first myocardial infarctions treated with thrombolysis. The Investigators of the Gruppo Italiano per lo Sudio della Sopravvivenza nell'Infarto Miocardico (GISSI-2). N Engl J Med 1993;329:1442–1448.
[Abstract/Free Full Text] - White HD, Barbash GI, Califf RM, Simes RJ, Granger CB, Weaver WD, Kleiman NS, Aylward PE, Gore JM, Vahanian A, Lee KL, Ross AM, Topol EJ. Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Circulation 1996;94:1826–1833.
[Abstract/Free Full Text] - ASSENT-2 Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Assessment of the Safety and Efficacy of a New Thrombolytic Investigators. Lancet 1999;354:716–722.[CrossRef][ISI][Medline]
- Wallentin L, Goldstein P, Armstrong PW, Granger CB, Adgey AA, Arntz HR, Bogaerts K, Danays T, Lindahl B, Makijarvi M, Verheugt F, Van de Werf F. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation 2003;108:135–142.
[Abstract/Free Full Text]
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