With respect to the article “Findings and Implications of the ROCKET Study,”1 we are in agreement with López-Sendón et al. that the findings2 support the decision of the health authorities to grant authorization of rivaroxaban,3,4 and that these results could help change stroke and systemic embolism prevention strategies in patients with atrial fibrillation, given that the new oral anticoagulants represent a major therapeutic advance. However, several aspects are of particular importance when assessing the clinical implications of the ROCKET study, and these deserve special attention.
The first is related to the efficacy of rivaroxaban vs warfarin. On this point, we have detected a contradiction in the text. In the section “Findings of the ROCKET Study,” the authors state that there were no significant differences in the efficacy endpoint in the intent-to-treat analysis, whereas in the section “Clinical Implications of the ROCKET Study,” they state that, cost permitting, the new anticoagulants should displace warfarin in the prevention of stroke in patients with atrial fibrillation in most cases, given their greater efficacy and ease of administration. In our opinion, regardless of the associated costs, this latter statement is incongruent given that rivaroxaban was not shown to be superior to warfarin.
Regarding the bleeding complications, we agree with the authors that rivaroxaban does not increase the risk of serious or clinically relevant bleeding compared to warfarin and significantly decreases intracranial and fatal bleeding. However, we find no allusion to the increase in severe gastrointestinal bleeding in the group treated with rivaroxaban compared to warfarin (odds ratio=1.60; 95% confidence interval, 1.29-1.98).5
Moreover, although it is true that the new oral anticoagulants represent major progress in medical treatment, we should nevertheless be aware of their limitations. In fact, although the lack of need for monitoring is considered an advantage, lack of follow-up could negatively affect adherence to treatment. In view of the short half-lives of these drugs, this aspect is of particular importance, as missed doses may quickly have an effect on the efficacy of treatment.6 Poor adherence could cancel out the potential clinical benefit of new oral anticoagulants compared to vitamin K antagonists and even increase the risk of stroke or systemic embolism. As observed in the ROCKET study, patients who discontinue treatment with rivaroxaban had a higher incidence of stroke or systemic embolism compared to those who discontinued warfarin.2 Likewise, other limitations, in no way insignificant, for the use of new oral anticoagulants are the lack of a specific antidote to reverse their effect and the limited experience in the management of bleeding complications in patients treated with these drugs.7 Finally, as with any other new drug, the available safety information is currently limited.
Thus, we do not agree with the authors when they state that the new oral anticoagulants should replace warfarin in most cases if costs allow. It is clear that the direct cost of treatment with new anticoagulants is markedly greater than treatment with vitamin K antagonists.8 However, economic motives are not the only reasons for caution in the use of these drugs, as there are also important aspects related to efficacy that are worthy of consideration.
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