title: Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome.
abstract: OBJECTIVE
  Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS.
  
  
  RESULTS
  The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial enrolled 9326 participants with ACS, who received aspirin plus clopidogrel or prasugrel. Median treatment exposure was 15 months. Cancer history and screening procedures were collected. Suspected non-benign neoplasm events were reported and adjudicated. The primary outcome was detection of new, non-benign neoplasm. Factors associated with neoplasm events, the relationship of these events to cardiovascular and bleeding endpoints, and treatment-related differences in neoplasm detection were studied. Among 9240 participants who received ≥1 dose of study drug, 1.8% had a confirmed neoplasm event. The efficacy composite of cardiovascular death, myocardial infarction, or stroke occurred more frequently among those with a neoplasm event vs. those without (18.2 vs. 13.5%) as did Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding (11.2 vs. 1.5%). Screening rates were substantially higher in North America and Western Europe/Scandinavia vs. other regions. Factors most strongly associated with detection of neoplasm events were older age, region, male sex, and current/recent smoking. Among the pre-specified population without a history of neoplasm or previous curative treatment for neoplasm (n = 9105), the incidence of neoplasm events was similar with prasugrel vs. clopidogrel (1.8 vs. 1.7%; HR = 1.04; 95% CI 0.77-1.42; P = 0.79).
  
  
  CONCLUSIONS
  Neoplasm events were infrequent during long-term DAPT after ACS, were associated with differential cancer-screening practices across regions, and the frequency of neoplasm detection was similar with prasugrel vs. clopidogrel.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00699998.
authors.affiliation: Duke Clinical Research Institute, 2400 Pratt Street, Rm 7035, Durham, NC 27705, USA Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA matthew.roe@duke.edu.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: Duke Clinical Research Institute, 2400 Pratt Street, Rm 7035, Durham, NC 27705, USA.
authors.forename: Derek D
authors.initials: DD
authors.lastname: Cyr
authors.affiliation: Duke Clinical Research Institute, 2400 Pratt Street, Rm 7035, Durham, NC 27705, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Eckart
authors.affiliation: Duke Clinical Research Institute, 2400 Pratt Street, Rm 7035, Durham, NC 27705, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Schulte
authors.affiliation: Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.affiliation: Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Blackwell
authors.affiliation: Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
authors.affiliation: Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: S Yousuf
authors.initials: SY
authors.lastname: Zafar
authors.affiliation: Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Anne W
authors.initials: AW
authors.lastname: Beaven
authors.affiliation: Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Strickler
authors.affiliation: Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Onken
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Houterloot
authors.affiliation: Daiichi Sankyo Development Ltd., London, UK.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zamoryakhin
authors.affiliation: Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.affiliation: Auckland City Hospital, Green Lane Cardiovascular Service, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India.
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.affiliation: British Heart Foundation Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Division of Cardiology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Duke Clinical Research Institute, 2400 Pratt Street, Rm 7035, Durham, NC 27705, USA Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D008134:Long-Term Care; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000401:mortality; D000072658:Non-ST Elevated Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Acute coronary syndrome; Adjudication; Antiplatelet drugs; Clinical trial; Clopidogrel; Neoplasm; Prasugrel; Surveillance