Matthew T Roe1, Derek D Cyr2, Debra Eckart2, Phillip J Schulte2, Michael A Morse3, Kimberly L Blackwell3, Neal E Ready3, S Yousuf Zafar3, Anne W Beaven3, John H Strickler3, Jane E Onken4, Kenneth J Winters5, Lisa Houterloot5, Dmitry Zamoryakhin6, Stephen D Wiviott7, Harvey D White8, Dorairaj Prabhakaran9, Keith A A Fox10, Paul W Armstrong11, E Magnus Ohman12. 1. 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. 2. Duke Clinical Research Institute, 2400 Pratt Street, Rm 7035, Durham, NC 27705, USA. 3. Division of Medicine - Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. 4. Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. 5. Eli Lilly and Company, Indianapolis, IN, USA. 6. Daiichi Sankyo Development Ltd., London, UK. 7. Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA. 8. Auckland City Hospital, Green Lane Cardiovascular Service, Auckland, New Zealand. 9. Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India. 10. British Heart Foundation Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK. 11. Division of Cardiology, University of Alberta, Edmonton, AB, Canada. 12. 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.
Abstract
AIMS: 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. METHODS AND RESULTS: The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial enrolled 9326 participants with ACS, who receivedaspirin 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00699998. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: 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. METHODS AND 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00699998. Published on behalf of the European Society of Cardiology. All rights reserved.
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