Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome

Eur Heart J. 2016 Jan 21;37(4):412-22. doi: 10.1093/eurheartj/ehv611. Epub 2015 Dec 5.

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 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.

Keywords: Acute coronary syndrome; Adjudication; Antiplatelet drugs; Clinical trial; Clopidogrel; Neoplasm; Prasugrel; Surveillance.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / mortality
  • Aged
  • Clopidogrel
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / mortality
  • Humans
  • Long-Term Care
  • Male
  • Neoplasms / complications*
  • Neoplasms / mortality
  • Non-ST Elevated Myocardial Infarction / complications
  • Non-ST Elevated Myocardial Infarction / drug therapy*
  • Non-ST Elevated Myocardial Infarction / mortality
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / therapeutic use*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00699998