Author + information
- Usman Baber, MD, MS,
- Jaya Chandrasekhar, MBBS, MS and
- Roxana Mehran, MD∗ ()
- ↵∗The Zena and Michael A. Wiener Cardiovascular Institute, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, New York 10029-6574
We thank Dr. Laine and colleagues for their comment on our recent analysis regarding the effect of prasugrel compared with clopidogrel in patients with and without chronic kidney disease (CKD) (1). Indeed, we agree that the conventional design of clinical trials typically excludes high-risk patients with CKD, thereby perpetuating a lack of experimental evidence to inform clinical decisions for such patients. Certainly, pragmatic trials have been used to address other questions in interventional cardiology (2–4) and there is every reason to expect success in studying a CKD patient population. However pragmatic trials may be disadvantaged in the ascertainment of certain endpoints such as bleeding. Furthermore, the issue of unselected consent for randomization in registry-based trials may be regarded as a sensitive matter (5). Nevertheless, these are surmountable problems in view of a just cause, given that CKD accounted for nearly 30% of all acute coronary syndrome percutaneous coronary intervention patients, as we noted in our study.
We agree with Dr. Laine and colleagues that our null findings with respect to differences between prasugrel and clopidogrel may reflect a type II error. Alternatively, preferential use of a more potent agent in lower risk patients might attenuate the expected benefit realized in the controlled setting of a randomized trial. Ultimately, questions surrounding efficacy must be answered by a randomized trial, because registries such as PROMETHEUS are naturally limited by issues of confounding and selection bias. To this end, the positive results reported in the CKD subgroup analysis from the PLATO (Platelet Inhibition and Patient Outcomes) trial are encouraging, but as noted by Laine and colleagues, cautious interpretation is warranted.
PROMETHEUS was successful in representing a large number of patients with CKD undergoing percutaneous coronary intervention for acute coronary syndrome and highlights the therapeutic malaise in prescribing potent therapy to this group. We hope that our results, along with others, focus efforts to pursue evidence-based treatments in patients with CKD.
Please note: The PROMETHEUS study was sponsored and funded by Daiichi Sankyo and Eli Lilly. Dr. Mehran has received institutional grant support from AstraZeneca, The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly/Daiichi Sankyo; and is a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck, and The Medicines Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- ↵Baber, U, Chandrasekhar, J, Sartori, S, et al. Associations between chronic kidney disease and outcomes with use of prasugrel versus clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a report from the PROMETHEUS study. J Am Coll Cardiol Intv 2017;10:2017–25.
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