• Duration of Dual Anti-Platelet Therapy After Percutaneous Coronary Intervention With Drug-Eluting Stents

    March 20, 2017

    By: Michael A. Kutcher, MD, FSCAI

    Dual anti-platelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, and ticagrelor) is a mainstay in the therapy of patients who undergo percutaneous coronary intervention (PCI) with either drug-eluting stents (DES) or bare-metal stents (BMS). We all get weekly or even daily communications from referring physicians, surgeons, or patients as to how long to stay on DAPT after DES or when can DAPT therapy be interrupted for a patient undergoing non-cardiac surgery. Such decisions can have significant implications on quality improvement and patient safety. This Tip-of-the-Month (TOTM) will summarize new recommendations on optimal DAPT duration and decision making tools, based on recently published focused guideline updates and systematic reviews. Now would be a good time to find a quiet place to sit, put your feet up, have a cup of coffee, and review the TOTM points – then be inspired to read the entire document in the above link and other references.


    The following points cover what is new in the topic of post PCI DAPT, especially with the use of DES.

    1. Updated recommendations for DAPT duration in patients with DES:

    • Optimal DAPT duration in patients who get a DES for stable ischemic heart disease is at least 6 months, as opposed to at least 12 months in the previous guidelines.
    • Optimal DAPT duration in patients who get a DES for acute coronary syndrome (ACS), which includes non-ST elevation myocardial infarction (NSTE-ACS) or ST elevation myocardial infarction (STEMI) is 12 months, unchanged from previous guidelines.

    See Flow Diagram and Arrows in Figure 1.  

     

     

    Figure 1 - Treatment Algorithm for Duration of P2Y12 Inhibitor Therapy in Patients Treated With PCI. Reproduced from Levine GN et al. J Am Coll Cardiol 2016; 68:1082-115

    2. Updated recommendations regarding interruption of DAPT in patients with DES undergoing surgery:

    • Interruption of DAPT before 3 months after DES is harmful.
    • Interruption of DAPT may be considered between 3-6 months after DES, if the risk of delaying surgery outweighs the risk of stent thrombosis.
    • Interruption or discontinuation of DAPT 6 months after DES is appropriate.
    • If at all possible, low dose aspirin should be continued if the P2Y12 agent is interrupted or discontinued.

    See Flow Diagram and Arrows in Figure 2. 

     

     

    Figure 2 - Treatment Algorithm for the Timing of Elective Noncardiac Surgery in Patients with Coronary Stents. Reproduced from Levine GN et al. J Am Coll Cardiol 2016;68:1082-115

    3. Assessment of ischemic and bleeding risk to aid in decision making regarding DAPT duration post DES in the individual patient:

    Factors which increase ischemic risk - may favor more prologned DAPT beyond standard time frames:

    • Advanced age
    • ACS presentation
    • Multiple prior MIs
    • Extensive coronary artery disease

    Factors which increased risk of stent thrombosis - may favor more prologned DAPT beyond standard time frames:

    • ACS presentation
    • Diabetes mellitus
    • Left ventricular ejection fraction <40%
    • First generation DES
    • Stent undersizing or underdeployment
    • Small stent diameter
    • Greater stent length
    • Bifurcation stents
    • In-stent restenosis

    The risk of ischemia or stent thrombosis must be weighed against the risk of increased bleeding with protracted DAPT therapy.

    Factors which increase bleeding risk - may favor a shorter duration DAPT than standard time frames:

    • History of prior bleeding
    • Oral anti-coagulant therapy
    • Female sex
    • Advanced age
    • Low body weight
    • Chronic kidney disease
    • Diabetes mellitus
    • Anemia
    • Chronic steroid or non-steroidal anti-inflammatory drugs

    4. Incorporation of ischemic and bleeding risk to calculate a DAPT score and using the DAPT score for decision making regarding duration of DAPT post DES:

     

    Calculating the DAPT Score [2]:  Points
    Age > 75 y -2
    Age 65 to < 75 y -1
    Age < 65 y  0
    Current cigarette smoker   1 
    Diabetes mellitus   1
    MI on presentation   1
    Prior PCI or MI   1
    Stent diameter < 3 mm   1
    Paclitaxel-eluting sent   1
    Congestive heart failur of LVEF <30%  2
    Saphenous vein graft PCI  2

    Using the DAPT Score for decision making:

    > 2 Favorable benefit/risk ratio for prolonged DAPT
    < 2 Unfavorable benefit/risk ratio for prolonged DAPT 

    There are other risk scores being developed, including the recently published PRECISE-DAPT Score from Costa et al [3] that may soon be available in a downloaded calculator.

    5. Additional Resources

    John Bittl was lead author on an in depth and insightful systematic review [4] that ran parallel with the published ACC/AHA Focused Update on Duration of DAPT. This is a useful series of various analyses that included forest plots, one of which compared 3-6 months of DAPT with 12 months of DAPT (Figure 1 in Bittl et al). There was no statistically significant difference in mortality, major hemorrhage, MI, stent thrombosis, and overall major adverse cardiovascular events. Shorter DAPT had a trend of slightly better mortality and reduction of major hemorrhage. Prolonged DAPT had trends of reduction of MI and stent thrombosis.Finally, Guistino et al [5] recently published an article on the efficacy and safety of 3-6 month DAPT versus 12 month or greater DAPT in patients with complex PCI. Complex PCI was defined as 3 vessels treated, > 3 stents implanted, > 3 lesions treated, bifurcation with 2 stents implanted, total stent length > 60 mm, or chronic total occlusion (CTO).

    The results are depicted in the schema below in Figure 3.

     

     

    Figure 3 - The y-axis displays the adjusted hazard rations for long-term DAPT on major adverse cardiac events (composite of cardiac death, MI, stent thrombosis). The x- axis displays the number of high-risk procedural features. The difference in the incidence rate of MACE between 3-6 months DAPT vs. 12 months DAPT increases with PCI complexity. Reproduced from Giustino et al. J Am Coll Cardio 2016;68(17):1851-1864.


    Summary

    • The recently published 2016 Focused Updated on Duration of DAPT in patients with coronary artery disease and Systematic Review are important resources to guide therapeutic DAPT duration decisions in patients with DES.
    • The full effect of these guidelines and other articles are beyond the scope of this Tip-of-the-Month. The intent however is to stimulate colleague interest in reading these publications.
    • Patient risk for stent thrombosis versus 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

     

    References:

    1. Levine GN, Bates ER, Bittl JA, et al. Focused Update Writing Group, 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. Cardiol J. 2016; 68(10):1082-1115.

    2. Yeh RW, Secemsky E, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond one year after percutaneous coronary intervention: an analysis from the randomized Dual Antiplatelet Therapy Study. JAMA. 2016; 315(16):1735-1749.

    3. Costa F, van Klaveren D, James S, et al. Derivation and validation of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials.Lancet.. 2017; 389:1025-1034. 

    4. Bittl JA, Baber U, Bradley SM, et al. Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease, Journal of the American College of Cardiology. 2016; doi: 10.1016/j.jacc.2016.03.512.

    5. Giustino G, Chieffo A, Palmerini T, et al. Efficacy and safety of dual antiplatelet therapy after complex PCI.Cardiol J. 2016; 68(17):1851–64.