Response Response

To the Editor:

We thank Dr. Berjón for his comments about the convenience of carrying out a clinical trial to determine the best reperfusion treatment in the elderly, and which he considers unnecessary and inappropriate. This consideration is based mainly on the meta-analyses which sustain that primary angioplasty (PA) is superior to fibrinolysis for the management of acute myocardial infarction (AMI). The author comments that the need for a study is due to the existence of data that suggest the possibility of a different result in older patients as compared with the general population, since the success of PA is independent of age. However, the fact is that, although the angiographic success is high for all ages, the resolution rates of the ST segment and myocardial perfusion after PA fall progressively with age and they are associated with a proportional increase in mortality.¹ Furthermore, although some studies indicate that the benefit of PA as compared with fibrinolysis is greater in older patients, other studies are contradictory.² Strangely, he fails to mention that most of the clinical trials comparing PA with fibrinolysis excluded patients who were older than 75 years of age or included just very small proportions of these patients, and that several observational studies suggest that the benefit of PA over fibrinolysis is not as clear in real life as in the clinical trials.³ He states that, according to the meta-analysis of the Fibrinolytic Therapy Trialists, fibrinolysis significantly reduces mortality in 16% of patients aged over 75 years. However, a later study, based on patients aged over 75 years with the current selection criteria, i.e., ST segment elevation or left bundle branch block with admission within the first 12 hours, revealed an absolute reduction in death of 3.4% (from 29.4% to 26%; relative risk reduction [RRR], 15%; P=.03), which represents 34 lives saved for every 1000 patients older than 75 years of age treated.⁴ Dr. Berjón criticizes the undertaking of a clinical trial that compares PA with fibrinolysis in the elderly, when the overall benefit shown by PA as compared with fibrinolysis in the whole population is lower than that shown by fibrinolysis in this same age group. It therefore remains to be determined whether selection of an older population for this new study is justified. To this extent, it is noteworthy that the lead author of the meta-analysis that Dr. Berjón uses as an argument to defend that PA is superior to fibrinolysis in the subgroups at greatest risk, including the elderly,⁵ is not so convinced as he is of this statement. In fact, it was she who promoted the first large clinical trial to compare PA and fibrinolysis in older patients (SENIOR PAMI). Unlike the predictions of Dr. Berjón, this study was unable to demonstrate that PA is superior to fibrinolysis in patients aged over 70 years with AMI of less than 12 hours evolution. Thus, the incidence of the primary endpoint (death or incapacitating stroke at 30 days) was 11.3% with PA and 13% with fibrinolysis (P=.57). This difference was greater in the patients aged from 70 to 80 years (7.7% vs 12%; P=.18), but in the patients aged over 80 years, those at highest risk, no clear benefit of PA over fibrinolysis could be demonstrated (C. Grines, personal communication, TCT, Washington, October 2005).

Dr. Berjón argues that fibrinolysis presents a risk of stroke (5.5% in TRIANA 2),⁶ but he nevertheless fails to mention the much more favorable results of the latest clinical trials on fibrinolysis (e.g., 0.8% with tenecteplasa in combination with unfractionated heparin in ASSENT-3 PLUS).⁷ On the other hand, when he questions whether the clinical trial should be carried out in centers that have PA, he fails to consider the important information that the TRIANA Registry collected in those Spanish centers with PA: 42% of the patients aged 75 years or over, with AMI and ST segment elevation, did not receive any reperfusion treatment and that, among those who did receive this treatment, the most used was fibrinolysis. Only 1 in every 5 patients received treatment with PA.⁶ Thus, even although the information showed that PA is superior to fibrinolysis in older patients, this indication has not been incorporated into daily clinical practice in Spain, which strengthens interest in this study.

We agree with the technical considerations concerning the design of a relatively small clinical trial to compare fibrinolysis with PA in older patients, but we disagree that its inability to provide a definitive response to the question reduces the usefulness of the study. Studies that do not by themselves provide a definitive response are very necessary, in order to obtain the results of the meta-analysis upon which Dr. Berjón bases his opinion. Our posture is modest. We recognize that a not very large clinical trial may not provide a definitive response to the question considered, but we believe that it will be of use, in conjunction with other studies, to help take clinical decisions in such a complex and controversial subject as is reperfusion in the older patient with AMI.