To the Editor:
First of all, we would like to congratulate the authors of the Update of the Guidelines of the Spanish Society of Cardiology for Unstable Angina/Without ST-Segment Elevation Myocardial Infarction (ACSWESR)1 for undertaking the enormous and difficult task that an update of this type entails with the thankless certainty that it will never reach total consensus. In this respect, I would like to remark on some points in the section on antiplatelet aggregation treatment, specifically the use of clopidogrel.
In the first place, a class I indication for clopidogrel is established in patients with ACSWESR of intermediate and low risk. In contrast, in high-risk patients the risk-benefit relation must be assessed when they receive treatment with glycoprotein IIb/IIIa inhibitors, since it is stated that the effects of the association are not known at present. Paradoxically, this lack of a clear position contrasts with the reality that the greatest benefit of clopidogrel in absolute terms is obtained in the high-risk group,2,3 according to the TIMI risk classification. Clopidogrel reduces the absolute risk (AR) of death, infarction, or stroke by 4.8% (placebo, 20.7% vs clopidogrel, 15.9%; P=.003), independent of any other type of coadjuvant treatment. In patients with low-to-intermediate risk, the reduction in AR, although significant, is lower in both, about 1.5%. The initial analysis of all the subgroups is consistent in the original article of the CURE study.4 With regard to the risk, there is no foundation for affirming in the present guideline, as the results that will be developed more below show,2,3 that the groups that benefited most were patients of intermediate and low risk.
Although no prospective study has evaluated primarily the benefit/risk of the association of clopidogrel and glycoprotein IIb/IIIa inhibitors, it cannot be claimed that the effects of this combination are not known. The patients of the TARGET trial5 who received preliminary treatment (2-6 h before percutaneous revascularization) with 300 mg of clopidogrel, showed a significant reduction in the incidence of death, infarction, or urgent revascularization in the first 30 days in both the tirofiban group (7.2% vs 12.5%; P<.001) and the abciximab group (5.8% vs 8.3%; P=.026). Likewise, in the EPISTENT study,6 previous treatment with ticlopidine of patients who were treated with abciximab reduced the need for revascularization in the first year (RR, 0.62; P=.01). With regard to the safety of the association, in the PCI-CURE trial,7 clopidogrel did not increase the incidence of major hemorrhage in patients that received a glycoprotein IIb/IIIa inhibitor: 2.2% in the clopidogrel group versus 2.2% in the placebo group. Similarly, in the above-mentioned EPISTENT study,6 the percentage of hemorrhage was identical to that seen with the association of abciximab and ticlopidine: 1.5% vs 1.5% with abciximab alone. In other studies, the combination of clopidogrel or ticlopidine with different glycoprotein IIb/IIIa antagonists has not increased average bleeding time with respect to that observed with glycoprotein IIb/IIIa antagonists alone.5,8,9
It is also surprising that after admitting the benefit of previous treatment with clopidogrel in patients treated with percutaneous revascularization, its indication is limited to class I under the assumption that the patients have not been treated with glycoprotein IIb/IIIa inhibitors or in every case in the first 30 days after angioplasty. The evidence is clear: the greatest benefit of clopidogrel is obtained by administering it at least 2 h before revascularization5,7 rather than during the intervention or afterward. On the other hand, PCI often cannot be performed in the first 24 h, which thus eliminates the early benefit of clopidogrell4 in these high-risk patients.
In my opinion, the indication for clopidogrel treatment in patients with high-risk ACSWESR should be class I, as well as for previous treatment in the case of intended PCI. This view is consistent with ACSWESR guidelines published recently by the ACC/AHA.10