Secondary prevention of acute coronary events with antiplatelet agents (SPACE-AA): One-year real-world effectiveness and safety cohort study in the French nationwide claims database

Atherosclerosis. 2019 Feb:281:98-106. doi: 10.1016/j.atherosclerosis.2018.11.037. Epub 2018 Dec 7.


Background and aims: We aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing.

Methods: We performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment.

Results: 54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59-0.90] and composite criterion (0.88, 95% CI [0.79-0.99] but not ACS 0.92 [0.80-1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82-1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients.

Conclusions: Ticagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel.

Keywords: Acute coronary syndrome; Claims database; Cohort study antiplatelet agents; Secondary prevention; Ticagrelor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy*
  • Administrative Claims, Healthcare
  • Aged
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Comparative Effectiveness Research
  • Databases, Factual
  • France / epidemiology
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / adverse effects
  • Prasugrel Hydrochloride / therapeutic use*
  • Recurrence
  • Risk Factors
  • Secondary Prevention*
  • Ticagrelor / adverse effects
  • Ticagrelor / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor