Author + information
- Francesco Costa, MD and
- Marco Valgimigli, MD, PhD∗ ()
- ↵∗Thoraxcenter, Ba 587, Erasmus Medical Center, ‘s Gravendijkwal 230, Rotterdam 3000CA, the Netherlands
We read with interest the paper by Yeh et al. (1) published in the Journal, reporting on a subgroup analysis from the DAPT (Dual Antiplatelet Therapy) trial in which the effect of an extended treatment with DAPT beyond 1 year was investigated in patients presenting with or without myocardial infarction at the time of stent implantation. The authors concluded that the benefit of an extended treatment persisted irrespective of the clinical presentation.
We believe the results of this analysis only poorly support this conclusion for the following motivations. Reducing mortality is the ultimate goal of cardiovascular medicine. However, the use of combined endpoints, encompassing fatal and nonfatal events, such as myocardial infarction or cerebrovascular accident, is necessary to increase study power and limit the number of patients needed in clinical trials. Death traditionally comprises a small fraction of such composite outcomes after percutaneous coronary intervention. Therefore, the underlying foundation for combining fatal and nonfatal outcomes as a reliable measure of a given treatment effect requires that nonfatal endpoints are independently associated with fatal events and that the strength of this association is somewhat comparable across nonfatal endpoints. The rationale for extending DAPT beyond the recommended period is to prevent myocardial infarction, both stent- and nonstent-related, and by that improving survival.
In contrast, the DAPT study showed an increase in mortality by an extended course of treatment, and the subgroup analysis by Yeh et al. (1) strongly suggests that the excess of fatality originates from patients presenting without myocardial infarction. In this patient subset, prolonged DAPT duration was associated to a 43% mortality increase. However, the interaction testing for mortality did not reach the formal level of significance (Pint: 0.13). Importantly, interaction testing is known to be underpowered, and it greatly increases the risk of incorrectly concluding that no interaction effect exists when in reality it does (2). When we calculated the power of detecting such interaction in the DAPT study as suggested by Brookes et al. (3) this was roughly as low as 29%.
Misinterpreting such a finding, which has indeed a plausible biological explanation (i.e., patients without prior myocardial infarction are at lower risk for ischemic recurrences, show lower platelet reactivity, and have potentially higher rate of bleeding when treated with prolonged antithrombotic therapy) (4), may expose a large number of patients to unnecessary bleeding events, which do carry prognostic implications and may ultimately worsen outcomes.
Defining which subgroups of patients derive a benefit and which harm from an extended DAPT regimen is urgent, given the level of uncertainty clearly voiced by the medical community (5).
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Yeh R.W.,
- Kereiakes D.J.,
- Steg P.G.,
- et al.
- Costa F.,
- Vranckx P.,
- Leonardi S.,
- et al.