Ticagrelor vs Clopidogrel in high bleeding risk patients with ACS

Ticagrelor vs clopidogrel use in high bleeding risk in hospitalized patients with acute coronary syndrome: Findings from the CCC–ACS project.

Wang Y, et al. Thromb Res. 2022;216:43–51.

Key Takeaway

• This large observational, real–world study of patients from Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) project, compared the use of ticagrelor vs clopidogrel in ACS patients at high bleeding risk (HBR) and identified that:
  • Clopidogrel was prescribed more frequently than ticagrelor
  • No significant difference in the risk for in–hospital MACCE between ticagrelor and clopidogrel groups
  • Ticagrelor* was associated with significant increase in the rate of in–hospital TIMI major / minor bleeding (by 25%) and in–hospital ICH (by 50%)
    • Subgroup analyses showed highest rate of major bleeding with a ticagrelor loading dose
  • Rates of in–hospital stent thrombosis (ST) and MI were low and similar in both groups, suggesting that clopidogrel might not expose patients to more ischemic risks

Why This Matters

• Current guidelines recommend ticagrelor over clopidogrel for patients with ACS, regardless of plans for invasive management.
  • However, use of guideline recommendations to treat ACS patients at HBR might be challenging due to a higher risk of bleeding events
  • Such patients are under–represented / excluded in large clinical trials, resulting in very less clinical evidence to guide optimal choice of a P2Y12 inhibitor
• This study evaluated the efficacy and safety of ticagrelor and clopidogrel among real–life ACS patients with HBR during hospitalization.

Study Design

• A total of 1,13,650 patients with ACS were registered in CCC–ACS database^†
• Patients were divided into non–HBR and HBR groups^‡
• Overall, 22,120 patients were identified as HBR • Patients were treated with DAPT^§ (aspirin + ticagrelor or clopidogrel)
• Outcomes assessed:
  • Primary efficacy endpoint: In–hospital MACCE (defined as a composite of all–cause death, MI, ST, or ischemic stroke during hospitalization)
  • Primary safety endpoint: In–hospital TIMI major^¶ or TIMI minor^# bleeding
  • Secondary endpoints: Individual components of MACCE, TIMI major and minor bleeding, ICH, or GI bleeding

Key Results

• Among 22,120 ACS patients categorized as HBR, majority were prescribed clopidogrel (78.8%) and only 21.2% were prescribed ticagrelor.
• Baseline characteristics: Well balanced between the groups after propensity score matching
• Median in–hospital duration: 10 days (IQR = 7–14 days)

Primary efficacy endpoint:

	Ticagrelor (%)	Clopidogrel (%)	OR|| (95% CI)	P-value	Interpretation
MACCE	4.2	4.3	1.08 (0.90-1.28)	0.411	No significant difference between ticagrelor and clopidogrel groups
All-cause death	3.9	3.5	1.17 (0.97-1.41)	0.107
Myocardial infraction	0.6	0.6	1.17 (0.75-1.83)	0.483
Stent thrombosis	0.1	0.1	0.90 (034-2.43)	0.839
Ischemic stroke	0.3	0.5	0.62 (0.34-1.14)	0.125

Primary safety endpoint:

Propensity scores matched cohort: Outcomes consistent with main analysis

Subgroup analysis

Parameter	Interpretation
In-hospital MACCE	Differences in all subgroup analyses were non-significant
In-hospital TIMI major or minor bleeding	Higher risk with ticagrelor treatment observed in patients with hypertension (P = 0.022) and diabetes mellitus (P = 0.040)

Cross analysis by type and dosage of P2Y12 inhibitor:

Cross analysis by type and dosage of P2Y12 inhibitor
Adjusted risks (vs patients who did not receive a loading dose of clopidogrel)
	Outcome	P-value
Loading dose of clopidogrel	Increased risk of in-hospital MACCE	0.004
	Increased risk of all-cause death	0.001
Loading dose of ticagrelor	Increased risk of in-hospital MACCE	0.018
	Increased risk of all-cause death	0.001
	High in-hospital TIMI major or minor bleeding	0.006
	High TIMI major bleeding	0.021
	High Intracranial bleeding	0.007
	High GI bleeding	0.009

Limitations

• Only Chinese patients were included in the study; special attention is required while interpreting and expanding the results to Western patients.
• Despite of adjusting for a variety of known variables, unmeasured confounders were still possible.
• HBR was defined according to modified ARC–HBR criteria, which might lead to an underestimation of the prevalence of HBR patients.
• Study focused only on in–hospital outcomes

For additional details, please refer to the source publication Wang Y, et al.

* When compared with clopidogrel
† Between 01-NOV-2014 and December 30, 2019, from 240 hospitals (Unique identifier: NCT02306616)
‡ According to modified ARC–HBR criteria
§ Without P2Y12 inhibitor cross–over during hospitalization
¶ If any intracranial or fatal bleeding or clinical signs of hemorrhage with Hb: ≥5 g/dL
# Clinical signs of hemorrhage with Hb: 3–5 g/dL
|| Adjusted value

MAT-BH-2300024/V1/JAN2023