Net clinical benefit of clopidogrel plus aspirin vs ticagrelor plus aspirin following percutaneous coronary intervention in patients in China with acute coronary syndrome

This retrospective, real-world study in Chinese acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DESs) demonstrated that outpatient use of clopidogrel dual antiplatelet therapy (DAPT) was associated with reduction in net adverse clinical and cerebral events (NACCE) and bleeding.

Key Takeaway

  • This analysis of retrospective data obtained from preexisting databases evaluating patients with ACS within 1-year post-PCI in mainland China reported the difference in net clinical benefit of antiplatelet treatment regimen.
    • Clopidogrel-based DAPT significantly lowered the risk of composite NACCE vs ticagrelor-based DAPT
    • Clopidogrel was comparable to ticagrelor in terms of major adverse cardiovascular events (MACE)
  • The real-world evidence provided by this study substantiated the clinical utility of clopidogrel plus aspirin as a viable treatment strategy.
    • Safety outcomes of ticagrelor and clopidogrel need to be investigated in randomized clinical trials with a longer follow-up period

Why This Matters

  • Current guidelines recommend the use of newer P2Y12 inhibitors like ticagrelor as an alternative for clopidogrel in the first-line treatment of ACS, unless there is an excessive risk of bleeding.
  • Previous reports indicated a differential frequency in the incidence of thromboembolic events in East Asian populations vs Western population.
  • This study evaluated the difference in net clinical benefit of clopidogrel + aspirin vs ticagrelor + aspirin after 12 months in patients in mainland China with ACS undergoing PCI with newer-generation DESs.

Study Design

  • Nationwide, multicenter, retrospective, non-interventional, real-world study involving 31 centers (data source: BRIC-ACS(I) study, COSTIC study, and 301 Hospital PCI patient database [January 2014 to October 2017])
  • Key inclusion criteria: Chinese patients with ACS aged ≥18 years who underwent second- or third-generation DES implantation and were treated with clopidogrel or ticagrelor plus aspirin with 12 months of follow up data
  • Primary endpoint: NACCE comprised of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and bleeding (as per the Bleeding Academic Research Consortium [BARC] type ≥2 [excluding BARC type 4])
  • Secondary endpoint: Evaluation of MACE and BARC type ≥2 bleeding events
  • Subgroup analysis: Age groups (<65 and ≥65 years) and data sources
  • Propensity score matching (PSM): Performed to minimize selection bias

Key Results

  • Overall, 7,236 patients with ACS were included (clopidogrel group [clopidogrel + aspirin]: n = 4,444; ticagrelor group [ticagrelor + aspirin]: n = 2,792)

Baseline characteristics before PSM

  • Patients in ticagrelor group (vs clopidogrel group) were younger (59.53 ± 10.19 vs 61.11 ± 10.68 years), and were more frequently male (76% vs 72.4%)

Clinical outcome before PSM (clopidogrel vs ticagrelor group):

  • NACCE: 269 (6.1%) vs 229 (8.2%)
  • Significantly reduced risk of NACCE occurrence (at 12 months): Adjusted hazard ratio (aHR) = 0.62 (95% confidence interval [CI]: 0.5–0.75; P <0.001)
  • No significant risk reduction in MACE outcomes: aHR = 0.8 (95% CI: 0.59–1.09; P = 0.157)
  • Bleeding events (BARC ≥2): 153 (3.4%) vs 149 (5.3%) patients (P <0.001)
  • Outpatient use of clopidogrel + aspirin significantly reduced risk of bleeding events vs ticagrelor + aspirin: aHR = 0.51 (95% CI: 0.39–0.66; P <0.001)
  • Marginal reduction in cumulative incidences of MACE: 2.9% vs 3.2% (P = 0.157)

Clinical outcome after PSM (clopidogrel vs ticagrelor group [2,165 patients from each group]):

  • Significantly lower cumulative incidence of NACCE (12-month follow-up): 117 (5.4%) vs 180 (8.3%); P <0.001
  • Reduced risk of NACCE (at 12 months): aHR = 0.61 (95% CI: 0.48–0.77; P <0.001)
  • Significantly lower incidence of bleeding (BARC ≥2) within 12 months: 62 (2.9%) vs 119 (5.5%); P <0.001
  • Significantly less risk of BARC-defined bleeding: aHR = 0.48 (95% CI: 0.35–0.66; P <0.001)
  • Incidence of MACE outcomes: Clopidogrel DAPT met prespecified non-inferiority criterion before and after PSM (absolute risk difference: −0.32 [95% CI: −1.14 to 0.5] and −0.28 [95% CI: −1.29 to 0.74], respectively)

Subgroup analysis:

  • Cumulative probability of NACCE: Statistically lower in clopidogrel group vs ticagrelor group in patients aged either <65 years (HR = 0.58 [95% CI: 0.41–0.81; P <0.001]) or ≥65 years (HR = 0.69 [95% CI: 0.50–0.95; P = 0.024])
  • Subgroup analysis data (age of patients and database) after PSM analysis: Consistent with the main findings (HR = 0.63 [95% CI: 0.50–0.80; P <0.001])


  • Patients were not randomized, and this would have introduced a selection bias (this was addressed to some extent by the PSM analysis)
  • All factors relating to Academic Research Consortium–High Bleeding Risk criterion could not be included in PSM analysis (due to data unavailability)
  • Data relating to post-discharge changes in DAPT regimen were not available
  • Bleeding severity is likely to be subject to adjudication error, as it was determined retrospectively

    Li D, Sun Y, Ye X, Li L, Chen Y, Wang D. Comparison of net clinical benefit between clopidogrel and ticagrelor following percutaneous coronary intervention in patients in China with acute coronary syndrome. Adv Ther. 2022;39(1):754–766. doi: 10.1007/s12325-021-01907-3. PMID: 34904209