Advertisement

Abbreviated Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy versus 12 Months’ Dual Antiplatelet Therapy Post Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis of Randomized Controlled Trials

  • Ashish KumarEmail author
  • Mariam Shariff
  • Rajkumar Doshi
  • Igor Pedreira Vaz
Original Research Article

Abstract

Introduction

An increased incidence of stent thrombosis after implantation of first-generation drug-eluting stents led to a recommendation of dual antiplatelet therapy (DAPT) for 12 months after the procedure. However, given the use of second-generation and newer drug-eluting stents, this recommendation needs to be revisited. Several randomized controlled trials (RCTs) have studied an abbreviated DAPT regimen of ≤ 3 months followed by P2Y12 inhibitor monotherapy, and results have been conflicting.

Objective

We performed a systematic review with meta-analysis of RCTs of abbreviated DAPT for ≤ 3 months followed by P2Y12 monotherapy compared with 12 months of DAPT.

Methods

We performed a systematic search of the MEDLINE/PubMed, Cochrane, and DARE (Database of Abstracts of Reviews of Effects) databases for eligible RCTs. Quantitative analysis was performed based on the intention-to-treat principle. We used the Mantel–Haenszel method with a random-effects model to calculate relative risks (RRs) with 95% confidence intervals (CIs).

Results

The final analysis included four RCTs. We found no difference in the risk of all-cause mortality (RR 0.90; 95% CI 0.77–1.05; p = 0.18; I2 = 0%; χ2p = 0.58), myocardial infarction (RR 0.99; 95% CI 0.86–1.15; p = 0.85; I2 = 0%; χ2p = 0.70), stroke (RR 1.14; 95% CI 0.65–1.98; p = 0.65; I2 = 59%; χ2p = 0.06), or stent thrombosis (RR 0.98; 95% CI 0.73–1.33; p = 0.90; I2 = 0%; χ2p = 0.48). Additionally, there was no difference in the risk for major bleeding, defined as BARC (Bleeding Academic Research Consortium) type 3 or 5, between the two groups (RR 0.62; 95% CI 0.37–1.05; p = 0.07; I2 = 79%; χ2p < 0.05).

Conclusion

Abbreviated DAPT followed by P2Y12 monotherapy resulted in a similar risk of re-ischemic clinical outcomes post percutaneous coronary intervention as compared with the standard 12-month DAPT regimen. The risk of major bleeding (BARC type 3 or 5) also remained similar between the two groups. However, as trials have reported benefits with abbreviated DAPT followed by P2Y12 monotherapy in terms of combined endpoints and all bleeding (BARC type 2–5), additional research is needed.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Ashish Kumar, Mariam Shariff, Rajkumar Doshi, and Igor Pedreira Vaz have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Supplementary material

40256_2019_390_MOESM1_ESM.docx (122 kb)
Supplementary material 1 (DOCX 121 kb)

References

  1. 1.
    Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155–66.  https://doi.org/10.1056/NEJMoa1409312.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Valgimigli M, Bueno H, Byrne RA, Collet J-P, Costa F, Jeppsson A, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European. Eur Heart J. 2017;39:213–60.  https://doi.org/10.1093/eurheartj/ehx419.CrossRefGoogle Scholar
  3. 3.
    Levin GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016;134(10):e123–55.  https://doi.org/10.1161/CIR.0000000000000404.CrossRefGoogle Scholar
  4. 4.
    Palmerini T, Benedetto U, Bacchi-Reggiani L, Della Riva D, Biondi-Zoccai G, Feres F, et al. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet. 2015;385:2371–82.  https://doi.org/10.1016/s0140-6736(15)60263-x.CrossRefPubMedGoogle Scholar
  5. 5.
    Park TK, Song YB, Gwag HB, Jang WJ, Yang JH, Hahn J-Y, et al. Aspirin versus clopidogrel following dual antiplatelet therapy on the era of drug-eluting stents. J Am Coll Cardiol. 2014;63:1612.CrossRefGoogle Scholar
  6. 6.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRefGoogle Scholar
  7. 7.
    Rao G, Lopez-Jimenez F, Boyd J, D’Amico F, Durant NH, Hlatky MA, Howard G, et al. Methodological standards for meta-analyses and qualitative systematic reviews of cardiac prevention and treatment studies: a scientific statement from the American Heart Association. Circulation. 2017;136:e172–94.  https://doi.org/10.1161/cir.0000000000000523.CrossRefPubMedGoogle Scholar
  8. 8.
    Hahn J-Y, Song YB, Oh J-H, Chun WJ, Park YH, Jang WJ, et al. Effect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized clinical trial P2Y12 monotherapy vs DAPT and cardiovascular events in patient. JAMA. 2019;321:2428–37.  https://doi.org/10.1001/jama.2019.8146.CrossRefPubMedGoogle Scholar
  9. 9.
    Watanabe H, Domei T, Morimoto T, Natsuaki M, Shiomi H, Toyota T, et al. Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: the STOPDAPT-2 randomized clinical trial effect of 1- vs 12-month dual antiplatelet T. JAMA. 2019;321:2414–27.  https://doi.org/10.1001/jama.2019.8145.CrossRefPubMedGoogle Scholar
  10. 10.
    Vranckx P, Valgimigli M, Jüni P, Hamm C, Steg PG, Heg D, et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre. Lancet. 2018;392:940–9.  https://doi.org/10.1016/S0140-6736(18)31858-0.CrossRefPubMedGoogle Scholar
  11. 11.
    Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med. 2019;381(21):2032–42.  https://doi.org/10.1056/NEJMoa1908419.CrossRefPubMedGoogle Scholar
  12. 12.
    Lagerqvist B, James SK, Stenestrand U, Lindbäck J, Nilsson T, Wallentin L. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med. 2007;356:1009–19.  https://doi.org/10.1056/NEJMoa067722.CrossRefPubMedGoogle Scholar
  13. 13.
    Cannon CP, Harrington RA, James S, Ardissino D, Becker RC, Emanuelsson H, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010;375:283–93.  https://doi.org/10.1016/S0140-6736(09)62191-7.CrossRefPubMedGoogle Scholar
  14. 14.
    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.CrossRefPubMedGoogle Scholar
  15. 15.
    De Luca G, Damen SA, Camaro C, Benit E, Verdoia M, Rasoul S, et al. Final results of the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation stent (REDUCE) trial. EuroIntervention. 2019.  https://doi.org/10.4244/eij-d-19-00539.CrossRefPubMedGoogle Scholar
  16. 16.
    Traby L, Kollars M, Kaider A, Eichinger S, Wolzt M, Kyrle PA. Effects of P2Y12 receptor inhibition with or without aspirin on hemostatic system activation: a randomized trial in healthy subjects. J Thromb Haemost. 2016;14:273–81.  https://doi.org/10.1111/jth.13216.CrossRefPubMedGoogle Scholar
  17. 17.
    Armstrong PCJ, Leadbeater PD, Chan MV, Kirkby NS, Jakubowski JA, Mitchell JA, et al. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost. 2011;9:552–61.CrossRefGoogle Scholar
  18. 18.
    Kim C, Hong S-J, Shin D-H, Kim B-K, Ahn C-M, Kim J-S, et al. Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design. Am Heart J. 2019;212:45–52.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Critical Care MedicineSt John’s Medical College HospitalBengaluruIndia
  2. 2.Department of Internal MedicineUniversity of Nevada Reno School of MedicineRenoUSA
  3. 3.Department of Internal MedicineJackson Memorial Hospital/University of MiamiMiamiUSA

Personalised recommendations