Author + information
- Received January 18, 2017
- Accepted February 9, 2017
- Published online October 16, 2017.
- Usman Baber, MD, MSa,
- Jaya Chandrasekhar, MBBS, MSa,
- Samantha Sartori, PhDa,
- Melissa Aquino, MSa,
- Annapoorna S. Kini, MBBSb,
- Samir Kapadia, MDc,
- William Weintraub, MDd,
- Joseph B. Muhlestein, MDe,
- Birgit Vogel, MDa,
- Michela Faggioni, MDa,
- Serdar Farhan, MDa,
- Sandra Weiss, MDd,
- Craig Strauss, MDf,
- Catalin Toma, MDg,
- Anthony DeFranco, MDh,
- Brian A. Baker, PharmDi,
- Stuart Keller, BS Pharmj,
- Mark B. Effron, MDj,k,
- Timothy D. Henry, MDl,
- Sunil Rao, MDm,
- Stuart Pocock, PhDn,
- George Dangas, MD, PhDb and
- Roxana Mehran, MDa,∗ ()
- aDivision of Cardiology, Icahn School of Medicine at Mount Sinai, New York, New York
- bDivision of Cardiology, Mount Sinai Hospital, New York, New York
- cDivision of Cardiology, Cleveland Clinic, Cleveland, Ohio
- dDivision of Cardiology, Christiana Care Health System, Newark, Delaware
- eDivision of Cardiology, Intermountain Heart Institute, Salt Lake City, Utah
- fDivision of Cardiology, Minneapolis Heart Institute, Minneapolis, Minnesota
- gDivision of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- hDivision of Cardiology, Aurora Cardiovascular Services, Milwaukee, Wisconsin
- iDaiichi Sankyo, Parsippany, New Jersey
- jEli Lilly and Company, Indianapolis, Indiana
- kDivision of Cardiology, John Ochsner Heart and Vascular Center, Ochsner Medical Center, New Orleans, Louisiana
- lDivision of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California
- mDivision of Cardiology, Duke University, Durham, North Carolina
- nLondon School of Hygiene and Tropical Medicine, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Roxana Mehran, 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.
Objectives This study sought to compare clinical outcomes in a contemporary acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) cohort stratified by chronic kidney disease (CKD) status.
Background Patients with CKD exhibit high risks for both thrombotic and bleeding events, thus complicating decision making regarding antiplatelet therapy in the setting of ACS.
Methods The PROMETHEUS study was a multicenter observational study comparing outcomes with prasugrel versus clopidogrel in ACS PCI patients. Major adverse cardiac events (MACE) at 90 days and at 1 year were defined as a composite of death, myocardial infarction, stroke, or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Cox regression multivariable analysis was performed for adjusted associations between CKD status and clinical outcomes. Hazard ratios for prasugrel versus clopidogrel treatment were generated using propensity score stratification.
Results The total cohort included 19,832 patients, 28.3% with and 71.7% without CKD. CKD patients were older with greater comorbidities including diabetes and multivessel disease. Prasugrel was less often prescribed to CKD versus non-CKD patients (11.0% vs. 24.0%, respectively; p < 0.001). At 1 year, CKD was associated with higher adjusted risk of MACE (1.27; 95% confidence interval: 1.18 to 1.37) and bleeding (1.46; 95% confidence interval: 1.24 to 1.73). Although unadjusted rates of 1-year MACE were lower with prasugrel versus clopidogrel in both CKD (18.3% vs. 26.5%; p < 0.001) and non-CKD (10.9% vs. 17.9%; p < 0.001) patients, associations were attenuated after propensity stratification. Similarly, unadjusted differences in 1-year bleeding with prasugrel versus clopidogrel (6.0% vs. 7.4%; p = 0.18 in CKD patients; 2.6% vs. 3.5%; p = 0.008 in non-CKD patients) were not significant after propensity score adjustment.
Conclusions Although risks for 1-year MACE were significantly higher in ACS PCI patients with versus without CKD, prasugrel use was 50% lower in patients with renal impairment. Irrespective of CKD status, outcomes associated with prasugrel use were not significant after propensity adjustment. These data highlight the need for randomized studies evaluating the optimal antiplatelet therapy in CKD patients with ACS.
- acute coronary syndrome(s)
- chronic kidney disease
- long-term outcomes
- percutaneous coronary intervention
- prasugrel or clopidogrel
The PROMETHEUS study was sponsored and funded by Daiichi Sankyo and Eli Lilly and Company. Dr. Kini has served on the Speakers Bureau of the American College of Cardiology; and has received consulting fees from WebMD. Mr. Keller is a salaried employee of and owns stock in Eli Lilly and Company. Dr. Effron is a former employee of and currently owns stock in Eli Lilly and Company. Mr. Baker is an employee of Daiichi Sankyo. Dr. Henry has received research grant support from Eli Lilly and Daiichi Sankyo. Dr. Mehran has received institutional grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly and Company/Daiichi Sankyo; and has served as a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co., and The Medicines Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Baber and Chandrasekhar contributed equally to this work.
- Received January 18, 2017.
- Accepted February 9, 2017.
- 2017 American College of Cardiology Foundation