Clinical outcome of switching from Clopidogrel to Ticagrelor

Clinical outcomes of in-hospital switching from clopidogrel to ticagrelor in patients with ACS undergoing percutaneous coronary intervention.

This retrospective study suggests that in-hospital switching from clopidogrel to ticagrelor was associated with an increase in net adverse clinical events (NACEs), mainly due to higher incidence of clinically relevant bleeding in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

Key Takeaway

• This large-scale, real-world, retrospective study of contemporary patients with ACS undergoing PCI initially receiving clopidogrel demonstrated that:
  • Advanced age, previous stroke, previous PCI, and estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2 favored continuation of clopidogrel
  • Male sex, diabetes mellitus, lesion, lesion on left main artery (LM) and number of stents implanted were identified as positive predictors of the switching to ticagrelor
  • Switching to ticagrelor was associated with higher rate of NACE or Bleeding Academic Research Consortium (BARC) type 2/3/5 bleeding versus continuation of clopidogrel; without reduction in major adverse cardiovascular event (MACE) rate
• Switching from clopidogrel to ticagrelor should be taken cautiously.
• Further prospective randomized clinical trials are required to strategize such switching from clopidogrel to ticagrelor.

Why This Matters

• Due to incomplete evaluation of ischemic or bleeding risk upon hospitalization of patients with ACS, physicians first provide conservative antiplatelet treatment with clopidogrel instead of ticagrelor as a precaution to prevent potential harm.
  • Of note, clopidogrel is associated with lesser bleeding and fewer adverse events vs ticagrelor.
• After relevant clinical assessments during hospitalization, patients are often shifted from clopidogrel to ticagrelor.
• Clinical benefits of switching treatment from clopidogrel to ticagrelor in patients with ACS undergoing PCI remains controversial.

Study Design

• This real-world, single-center, retrospective study among patients with ACS undergoing PCI (at General hospital of Northern Theater Command [Shenyang, China] between March 2016–March 2018) evaluated independent predictors and long-term clinical outcomes of continuing clopidogrel vs switching to ticagrelor.
  • Inclusion criteria: Patients who received clopidogrel initially during hospitalization
  • Exclusion: Patients recruited in other clinical trials and those discharged from hospital without any record of clopidogrel or ticagrelor medication
  • Clinical outcomes: Primary outcome— NACEs^* at 12 months after discharge; secondary outcomes— each component of NACE^§

Key Results

Patients baseline characteristics

• Among 10,519 patients with ACS who underwent PCI initially treated with clopidogrel, 1,405 (13.4%) switched to ticagrelor during hospitalization.

• Patients who switched to ticagrelor:
  • Were younger, more likely to be male, and had fewer comorbidities such as hypertension, previous myocardial infarction (MI), previous PCI, previous stroke, and anemia vs those who continued clopidogrel (P <0.05 for all)
  • Had more lesions located on the LM and left anterior descending coronary artery, and more stents with a greater average length implanted
• Percentage of patients with a diagnosis of ST‐segment elevation MI was significantly higher in the group that continued clopidogrel treatment (P <0.05).

Predictors of switching to ticagrelor:Multivariate analysis— odds ratio

• Variates that were associated with continuation of clopidogrel included:

  • Age: 0.96 (95% confidence interval [CI]: 0.96–0.97); P <0.001
  • Previous stroke: 0.75 (95% CI: 0.62–0.91); P = 0.003
  • Previous PCI: 0.60 (95% CI: 0.51–0.70); P <0.001
  • eGFR <45 ml/min/1.73 m2: 0.39 (95% CI: 0.23–0.67); P <0.001
• Variates that were positive predictors of the switching to ticagrelor included:
  • Male sex: 1.29 (95% CI: 1.11–1.50); P <0.001
  • Diabetes mellitus: 1.24 (95% CI: 1.09–1.41); P <0.001
  • Culprit lesion on LM: 1.32 (95% CI: 1.24–1.41); P <0.001
  • Number of stents: 1.01 (95% CI: 1.01–1.02); P <0.001

Clinical outcomes (switched to ticagrelor [n = 1,405] vs continued clopidogrel [n = 9,114] at 12 months):

• Unadjusted analyses: Significantly higher incidence of NACE: 7.47% vs 6.03% (P = 0.035); BARC type 2/3/5 bleeding: 6.05% vs 3.20% (P <0.001); significantly lower rate of MACE: 1.21% vs 2.57% (P = 0.002)

• Multivariable adjustment: Differences in rate of NACE (HR— 1.51, 95% CI: 1.18–1.91; P <0.001) and clinically relevant bleeding (HR— 2.01, 95% CI: 1.52–2.66; P <0.001) remained statistically significant; however, no significant difference in risk of MACE or its components (P ˃0.05 for all)

Limitations

• Unmeasured confounding effect might exist between treatment groups due to observational nature of study
• Factors associated with switching medication were just “indicators”
• Study did not accurately evaluate adverse effects of P2Y12 inhibitors neither could quantify ticagrelor adherence over time; and study conclusion could not be extended to switching between P2Y12 inhibitors after discharge.

^*Defined as a composite of MACE (composite of cardiovascular death, MI, and stroke) and clinically relevant BARC type 2/3/5 bleeding).^§ Cardiovascular death (any death of a cardiac cause, unwitnessed death, or death of an unknown cause, stroke (local or systemic loss of neurologic function attributable to a central nervous system vascular cause lasting for at least 24 hour), MI (Fourth Universal Definition of MI guidelines).

MAT-BH-2300016/V1/JAN2023