• Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention With Drug-Eluting Stents: Update on When to Switch to Antiplatelet Monotherapy

    November 07, 2019

    By: Michael A. Kutcher, MD, FSCAI, and Faisal Latif, MD, FACC, FSCAI

    Introduction

    Dual antiplatelet therapy (DAPT) with aspirin (ASA) and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) is a standard therapeutic regimen to prevent stent thrombosis after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). The duration of DAPT has significant risk/benefit consequences and implications on quality improvement and patient safety. Since the last American College of Cardiology (ACC) and American Heart Association (AHA) PCI DAPT Guidelines were published in 2016,1 there has been an explosion of data regarding strategies to shorten the duration of DAPT. This Tip of the Month (TOTM) will place perspective on the most recent studies in comparison with the older guidelines—but with advice to address the current demands of contemporary decision processes.

    Review of Published ACC/AHA 2016 DAPT Duration Guidelines in DES patients1

    Stable ischemic heart disease (SIHD): Six months followed by monotherapy with ASA. Patients with a high bleeding risk (HBR) may be shortened to three months.

    Acute coronary syndromes (ACS): ACS without ST-segment elevation (NSTE-ACS) or ST-elevation myocardial infarction (STEMI): 12 months followed by monotherapy with ASA. Patients with an HBR may be shortened to six months.

    Patients requiring noncardiac surgery: Interruption of DAPT before three months after a DES is harmful. It may be considered between three to six months if the risk of delaying surgery outweighs the risk of stent thrombosis. Interruption or discontinuation of DAPT six months after a DES is appropriate, regardless of original clinical presentation. If at all possible, low-dose ASA should be continued if the P2Y12 agent is interrupted or discontinued.

     

    Risk Scores:

    DAPT Score: > 2, favorable benefit/risk ratio for prolonged DAPT; < 2, unfavorable benefit/risk ratio for prolonged DAPT

    PRECISE-DAPT Score: <25, non-HBR; > 25 HBR

     

    Most Recent Studies on DAPT Duration

    The inclusion of all PCI DAPT duration strategy studies since 2016 is beyond the purview of this TOTM. Various trials and registries assessing shorter durations of DAPT after PCI with advanced-generation DESs are ongoing and should be peer-review published within the ongoing year. The following are selected snapshots of the most recent impactful peer-reviewed publications:

     

    PRECISE-DAPT Study2

    A meta-analysis of 14,963 patients from eight randomized trials where the PRECISE-DAPT score was applied in complex versus noncomplex and long-DAPT versus short-DAPT DES patients. Long-term DAPT in non-HBR patients (< 25 score) reduced ischemic events in both complex and noncomplex PCI. Short-term-DAPT in both groups reduced bleeding and ischemia risk only in the HBR (> 25 score) patients.

     

    SENIOR Study3

    A multicenter trial of 12,604 patients > 75 years old were randomized to PCI with a bare-metal stent (BMS) or a platinum-chromium bioabsorbable polymer everolimus-eluting stent (PtCr-BP-EES) with one month of DAPT for SIHD and six months of DAPT for ACS. A strategy of PtCr-BP-EES and a short duration of DAPT were better than a BMS and a similar duration of DAPT with respect to the occurrence of all-cause mortality, myocardial infarction, stroke, and ischemia-driven target lesion revascularization.

     

    STOPDAPT-2 Trial4

    A multicenter Japanese trial of 3,045 patients who underwent PCI with implantation of a cobalt-chromium durable polymer (CoCr-DP-EES) were randomized to one month of DAPT followed by clopidogrel monotherapy or 12 months of DAPT with ASA and clopidogrel. The one-month strategy compared with the 12-month strategy resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority.

     

    SMART-CHOICE Trial5

    A multicenter Korean open-label trial of 2,993 patients who underwent PCI with a variety of durable polymer (DP) or bioabsorbable polymer (BP) DESs were randomized to receive ASA and a P2Y12 inhibitor for three months followed by P2Y12 inhibitor monotherapy alone or DAPT for 12 months. The three-month DAPT strategy followed by monotherapy with a P2Y12 inhibitor was noninferior to rates of major adverse events compared to the 12-month DAPT strategy.

     

    TWILIGHT Trial6

    A multicenter international trial of 9,006 HBR patients who underwent PCI with a variety of DESs were followed by three months of DAPT with ASA and ticagrelor. If at three months there were no bleeding or ischemic events, they were continued on ticagrelor and double-blind randomized to either ASA or a placebo. At one year, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding compared to ticagrelor plus ASA with no higher risk of death, myocardial infarction, or stroke.

     

    Summary

    • Patient risk for stent thrombosis versus the increased bleeding risk and the duration of DAPT will vary with patient clinical characteristics, acute versus stable presentation, complexity of coronary anatomy, type of DES, and bleeding/thrombotic scores.
    • Ongoing data for a shorter duration of DAPT and a switch to monotherapy at three months—and even one month after implantation of a newer-generation, thinner strut DP DES and BP DES—are intriguing and may very well justify a change in clinical practice.
    • There is emerging data that a P2Y12 agent may be a better choice than ASA for antiplatelet monotherapy after DAPT in a DES. If so, the type of P2Y12—clopidogrel, ticagrelor, or prasugrel—will be another issue.
    • From a medical-legal standpoint, the strategy for duration of DAPT after a DES should still follow the current 2016 ACC/AHA guidelines.
    • In certain select risk/benefit cases, it may be appropriate to further shorten DAPT. If so, the rationale should be well documented in the medical record and pertinent references cited.
    • The next Focused Update on Duration of DAPT after Coronary Stent Implantation should be very interesting and give more succinct guidance as to a safe and effective strategy based on more recent data.

     

    References

    1. Levine 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. J Am Coll Cardiol 2016;68(10):1082-1115.
    2. Costa F, van Klaveren D, Feres F, et al. Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting. J Am Coll Cardiol 2019;73(7):741–54.
    3. Varenne O, Cook S, Sideris G, et al. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. The Lancet 2018;391(10115):41–50.
    4. Watanabe H, Domei T, Morimoto 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. JAMA. 2019;321(24):2414-2427.
    5. Hahn J-Y, Song YB, Oh J-H, 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. JAMA. 2019;321(24):2428-2437.
    6. Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. [published online ahead of print September 26, 2019]. N Engl J Med. doi: 10.1056/NEJMoa1908419