Benefits of short-term DAPT followed by ticagrelor only after PCI for ACS
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.
References
1. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720–826. https://doi.org/10.1093/eurheartj/ehad191
2. Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e21–129. https://doi.org/10. 1016/j.jacc.2021.09.006
3. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361: 1045–57. https://doi.org/10.1056/NEJMoa0904327
4. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–15. https://doi.org/10.1056/NEJMoa0706482
5. Généreux P, Giustino G, Witzenbichler B, Weisz G, Stuckey TD, Rinaldi MJ, et al. Incidence, predictors, and impact of post-discharge bleeding after percutaneous coronary intervention. J Am Coll Cardiol 2015;66:1036–45. https://doi.org/10.1016/j.jacc.2015. 06.1323
6. Valgimigli M, Costa F, Lokhnygina Y, Clare RM, Wallentin L, Moliterno DJ, et al. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRACER) randomized trial. Eur Heart J 2017;38:804–10. https://doi.org/10.1093/eurheartj/ehw525
7. O’Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y12 inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation 2020;142:538–45. https://doi.org/10.1161/CIRCULATIONAHA.120.046251
8. Giacoppo D, Matsuda Y, Fovino LN, ’Amico D, Gargiulo G, Byrne G, et al. Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J 2021;42:308–19. https://doi.org/10.1093/eurheartj/ehaa739
9. Valgimigli M, Gragnano F, Branca M, Franzone A, Baber U, Jang Y, et al. P2y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials. BMJ 2021;373:n1332. https://doi.org/10.1136/bmj.n1332
10. Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, et al. Effect of ticagrelor monotherapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute coronary syndrome: the TICO randomized clinical trial. JAMA 2020;323: 2407–16. https://doi.org/10.1001/jama.2020.7580
11. Hong SJ, Lee SJ, Suh Y, Yun KH, Kang TS, Shin S, et al. Stopping aspirin within 1 month after stenting for ticagrelor monotherapy in acute coronary syndrome: the T-PASS randomized noninferiority trial. Circulation 2024;149:562–73. https://doi.org/10.1161/CIRCULATIONAHA.123.066943
12. Baber U, Dangas G, Angiolillo DJ, Cohen DJ, Sharma SK, Nicolas J, et al. Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS. Eur Heart J 2020;41:3533–45. https://doi.org/10.1093/eurheartj/ehaa670
13. Vranckx P, Valgimigli M, Odutayo A, Serruys PW, Hamm C, Steg PG, et al. Efficacy and safety of ticagrelor monotherapy by clinical presentation: pre-specified analysis of the GLOBAL LEADERS trial. J Am Heart Assoc 2021;10:e015560. https://doi.org/10.1161/JAHA.119.015560