To the Editor:

Thank you for the letter from Dr. V. Valentín, who remarks on one of the points for which it was difficult to reach a consensus in the update of the Guidelines.1

As is well known, the recommendations of the Clinical Practice Guidelines are established in a given moment, using the knowledge available at that time. They reflect the assessment by the members of the writing committee of the published data and their final consensus regarding different criteria, thus resulting in the recommendation most acceptable for all.

In order to reach this point, it is necessary to travel a road that is often complicated.

The first of the factors involved is the interpretation of data. Although it is easy to evaluate the statistical significance of the results of clinical trials through the P value, it is much more complex to evaluate clinical significance. This is particularly necessary when dealing with a single study (CURE2). The relative importance of the different endpoints (death, infarction, CVA) versus the overall objective must by analyzed.3 The impact on different subgroups of risk and the definition of events (in this case, the definition of infarction) also condition clinical repercussion.

As Dr. Valentín knows very well, the data from trials sometimes change between the first communication and later publications. When the guidelines were drafted, published data from the CURE study2 supported the effectiveness of clopidogrel in groups of intermediate and low risk, but the benefit in the high-risk group (18.0% with placebo versus 16.3% with clopidogrel; a benefit of 1.7% in absolute terms, 9.4% in relative terms) was not significant. The unit line exceeded confidence limits so this recommendation was not included as class I. The references cited in your letter had not been published when the manuscript was written.

The most important complication associated with the use of clopidogrel in ACS is hemorrhage, particularly in high-risk patients undergoing surgery. Percutaneous coronary interventions (PCI)4 have their clearest indication in association with the use of a glycoprotein IIb/IIIa inhibitor.5 We do not know of any study that has directly assessed the result of simultaneous use of acetylsalicylic acid, heparin, glycoprotein IIb/IIIa inhibitor, and clopidogrel in these patients before and during PCI, but it seems reasonable to think that this combination can increase the risk of hemorrhage if used systematically. This was the second reason for not including clopidogrel as class I in this group of patients in which glycoprotein IIb/IIIa is recommended.1

Surely in the near future, what was known at the time that the update of the guidelines was written will be modified by the appearance of new findings that will require a new review of these recommendations due to the appearance of clear and convincing evidence.