Benefits of short-term DAPT followed by ticagrelor only after PCI for ACS

11/07/2024

In a systematic review and meta-analysis among ACS patients undergoing drug-eluting stent implantation, ticagrelor monotherapy after ≤3 months of dual antiplatelet therapy (DAPT) reduced bleeding risk without increasing ischemic risk, compared with 12 months of ticagrelor-based DAPT.

This summary is based on the publication of Lee YJ, Shin S, Kwon SW, et al. - Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials. Eur Heart J. 2024 May 16:ehae249 [Online ahead of print]. doi: 10.1093/eurheartj/ehae249

Introduction and methods

Background

For patients with ACS who have undergone PCI with implantation of a drug-eluting stent (DES), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y₁₂ inhibitor, such as ticagrelor or prasugrel, for ≥12 months is recommended to prevent ischemic and thrombotic events [1-4]. However, long-term DAPT, especially when including potent P2Y₁₂ inhibitors, is associated with increased risk of major bleeding [3-6].

Although several meta-analyses have demonstrated the beneficial effect of short-term DAPT followed by P2Y₁₂ inhibitor monotherapy in patients after coronary revascularization [7-9], the included trials were characterized by heterogeneity with regard to, for example, type of P2Y₁₂ inhibitor, stent type, and clinical endpoints.

Aim of the study

The authors evaluated the efficacy and safety of short-term DAPT followed by ticagrelor monotherapy in patients with ACS undergoing DES implantation.

Methods

In this systematic review and meta-analysis, individual patient data were pooled from RCTs comparing short-term (≤3 months) DAPT (consisting of aspirin plus ticagrelor) followed by ticagrelor monotherapy with 12-month DAPT (consisting of aspirin plus ticagrelor) in ACS patients undergoing PCI with implantation of a new-generation DES (biodegradable polymer sirolimus-eluting stent). Two RCTs, both conducted in South Korea, fulfilled the prespecified inclusion and exclusion criteria: the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New-Generation Sirolimus-eluting Stent for Acute Coronary Syndrome; n=3056) and T-PASS (Ticagrelor Monotherapy in Patients Treated with New-generation Drug-eluting Stents for Acute Coronary Syndrome; n=2850) trials [10,11]. Median follow-up duration was 360 days (IQR: 360–360).

In addition, the authors performed a prespecified secondary aggregate data meta-analysis, which included data from the TICO and T-PASS trials combined with the ACS subgroup of 2 additional RCTs that met the inclusion criteria but enrolled both patients with ACS and chronic coronary syndrome (i.e., TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients After Coronary Intervention) and GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Antiplatelet Therapy After Stent Implantation) trials) [12,13].

Outcomes

The prespecified coprimary endpoints were: (1) primary ischemic endpoint, a composite outcome of all-cause mortality, MI, or stroke at 1 year; and (2) primary bleeding endpoint, consisting of major bleeding, defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 1 year. Secondary endpoints were: (i) net adverse clinical event, defined as a composite outcome of the primary ischemic and bleeding endpoints (all-cause mortality, MI, stroke, or BARC type 3 or 5 bleeding); (ii) composite outcome of cardiac death, MI, or stroke; (iii) all-cause mortality; (iv) cardiac death; (v) MI; (vi) stent thrombosis; (vii) stroke; (viii) target-vessel revascularization; (ix) BARC type 3 bleeding; and (x) BARC type 5 bleeding.

Main results

Coprimary endpoints

  • At 1 year, the incidence of the primary ischemic endpoint did not differ between patients receiving ticagrelor monotherapy after ≤3 months of DAPT (n=2953) and those receiving 12 months of ticagrelor-based DAPT (n=2953) (1.9% vs. 2.5%; adjusted HR: 0.79; 95%CI: 0.56–1.13; P=0.194). Heterogeneity between the 2 trials was negligible (I²=0%; Cochran’s Q=0.14; P=0.706).
  • The risk of the primary bleeding endpoint was lower in the ticagrelor monotherapy group than the ticagrelor-based DAPT group (2.4% vs. 4.5%; adjusted HR: 0.54; 95%CI: 0.40–0.72; P<0.001). Heterogeneity between the 2 trials was substantial (I²=69%; Cochran’s Q=3.21; P=0.073), while the individual trial results were directionally consistent.
  • Prespecified sensitivity analyses based on a two-stage approach indicated the treatment effects were consistent across subgroups stratified by age, sex, hypertension, diabetes mellitus, CKD, clinical presentation, multivessel disease, or total stent length.

Secondary endpoints

  • The incidence of the net adverse clinical event was lower in the ticagrelor monotherapy group than the ticagrelor-based DAPT group (4.1% vs. 6.4%; adjusted HR: 0.64; 95%CI: 0.51–0.81; P<0.001).
  • BARC type 3 bleedings occurred less frequently in the ticagrelor monotherapy group than the ticagrelor-based DAPT group (2.3% vs. 4.4%; adjusted HR: 0.53; 95%CI: 0.40–0.71; P<0.001).
  • For the remaining secondary endpoints, the frequency did not differ between the treatment groups (all P>0.05).

Secondary aggregate data meta-analysis

  • In a prespecified secondary aggregate data meta-analysis of ACS patient groups from 4 RCTs, the risk of the primary ischemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups (HR: 0.92; 95%CI: 0.79–1.07; P=0.304) (I²=0%; Cochran’s Q=1.27; P=0.736).
  • Once more, the occurrence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group than in the ticagrelor-based DAPT group (HR: 0.54; 95%CI: 0.44–0.67; P<0.001) (I²=53%; Cochran’s Q=6.41; P=0.093).

Conclusion

In this systematic review and meta-analysis among ACS patients undergoing PCI with DES implantation, ticagrelor monotherapy after short-term (≤3 months) DAPT was associated with fewer major bleedings and no concomitant increase in ischemic events than 12 months of ticagrelor-based DAPT.

Find this article online at Eur Heart J.

References

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