Time Course of Death After Acute Coronary Syndrome Treated With Dual Antiplatelet Therapy for 1 Year

Am J Med. 2023 May;136(5):484-488. doi: 10.1016/j.amjmed.2023.01.029. Epub 2023 Feb 23.

Abstract

Background: Excess mortality remains the cornerstone concern despite dual antiplatelet therapy (DAPT) after acute coronary syndrome. Some data suggest that shorter periods than 12 months of DAPT diminish bleeding risks yet still provide adequate vascular protection and improving survival. However, the precise timing of deaths after acute coronary syndrome has not been mapped in many studies. This knowledge may be critical for defining optimal treatment duration.

Methods: Access was gained to the data set for the Platelet Inhibition and Outcomes (PLATO) trial, which was issued by the Food and Drug Administration, in which post hoc analyses of timing of death events during DAPT (with either aspirin/ticagrelor or aspirin/clopidogrel) were performed. All-cause individual deaths were counted and plotted over time from day 1 to day 365 after the index event.

Results: Among 18,624 enrollees, 938 total deaths were reported to the Food and Drug Administration in PLATO. After exclusion of deceased patients with missing dates, randomization errors, and deaths beyond 1 year of follow-up, 913 fatalities (509 after clopidogrel and 404 after ticagrelor) were analyzed. The PLATO records did not indicate where exactly deaths occurred making impossible to triage in the hospital versus outpatient fatalities. Most frequent deaths occurred within the Day 1 (n = 41); Day 2 (n = 48); and Day 3 (n = 33) and overall during the first week (n = 202; 22.1%) after the index acute coronary syndrome, with a gradual decline after Day 10 and Day 60, reaching background counts after Day 220.

Conclusion: Focusing on mortality reduction, this large data set may support a shorter than 12 months' duration of DAPT.

Keywords: Antiplatelet therapy; Clopidogrel; Death; Mortality; Risks; Ticagrelor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome*
  • Aspirin / therapeutic use
  • Clopidogrel / therapeutic use
  • Drug Therapy, Combination
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy
  • Humans
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Ticagrelor / therapeutic use
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor
  • Ticlopidine
  • Aspirin