2017 ESC Focused update on Dual Antiplatelet Therapy (DAPT)
D. Milasinovic reviews the 2017 Focused update on DAPT
As dual antiplatelet therapy (DAPT) seems to have been interventionalists’ close companion since the pioneering studies showing its benefits over oral anticoagulants (OAC) some 20 years ago, the myriad of ensuing studies has led to expanding indications, but has also uncovered the inherent risks of DAPT. In the 2017 Focused Update, the hitherto accumulated evidence is eloquently summarized into a set of recommendations that provide guidance on some of the important questions of an interventional cardiologist's everyday practice: which of the currently available P2Y12 inhibitors should be selected, what is the optimal duration of DAPT and how to manage bleeding complications.
Selection of P2Y12 inhibitors
The advent of new, more potent antiplatelet agents (prasugrel, ticagrelor), has raised the question of how far should we go in preventing ischemic events, if it comes at a cost of increased bleeding-related mortality. Therefore, the guidelines propose a selection algorithm that takes into account A) clinical presentation and B) timing of administration.
A) Clinical presentation:
- In patients with stable coronary artery disease (CAD), clopidogrel is recommended (ticagrelor and prasugrel have not been randomly compared to clopidogrel in this setting).
- In patients with acute coronary syndrome (ACS), the use of ticagrelor is recommended, regardless of the pre-treatment with clopidogrel, which should be discontinued upon starting with ticagrelor. Prasugrel is also preferred over clopidogrel,which in turn is recommended if ticagrelor or prasugrel cannot be used.
- In patients on OAC, clopidogrel is preferred.
- In STEMI patients treated with thrombolysis, clopidogrel is recommended.
B) Timing of administration:
- Pre-treatment with a P2Y12 inhibitor is recommended if the coronary anatomy is known and PCI indicated, or in STEMI.
- Ticagrelor (or clopidogrel if ticagrelor cannot be used) should be administered as soon as possible in patients with NSTE-ACS.
- In stable patients with a high likelihood of PCI, pre-treatment with clopidogrel may be considered.
- In NSTE-ACS with unknown coronary anatomy, Prasugrel is not recommended.
Even though switching between different P2Y12 agents is of considerable clinical interest, outcome data are available only for switching from clopidogrel to ticagrelor in the acute setting, which is recommended to take place early after hospital admission, with 180mg loading dose of ticagrelor, irrespective of the dose and the timing of clopidogrel administration.
Optimal duration of DAPT
Extending DAPT over a longer period of time may confer benefit in terms of reduction in spontaneous myocardial infarction (MI), albeit at the cost of increased bleeding risk. Thus, the new guidelines propose two risk stratification tools, that have specifically been developed to address the issue of DAPT duration – DAPT and PRECISE-DAPT scores. In patients with PRECISE-DAPT ≥25, the risk of bleeding is high, favoring shorter DAPT, whereas in cases of DAPT ≥2 the ischemic seems to outweigh the bleeding risk, suggesting possible benefit of prolonged DAPT.
Keeping in mind the need to always balance between ischemic and bleeding risks in an individual patient, the recommended duration of DAPT after PCI will strongly depend on the baseline clinical and angiographic/procedural information:
- In patients with stable CAD, DAPT is recommended for 6 months, irrespective of the stent type (and including drug-coating balloons). For patients with high bleeding risk, 3 months should be considered, or even only 1 month may be used (hitherto shown for zotarolimus-eluting Endeavor sprint stent and drug-coated stent). In case of low bleeding, but high thrombotic risk, DAPT may be prolonged >6 and ≤30 months. If bioresorbable scaffold (BRS) was implanted, DAPT should be used for at least 12 months.
- In patients with ACS, DAPT is recommended for 12 months. However, in case of high bleeding risk, discontinuation of DAPT at 6 months should be considered. Extending DAPT beyond 12 months may be considered, in patients without a bleeding complication. If BRS was implanted, at least 12 months of DAPT should be considered.
- In patients on oral anticoagulants (OAC), it is recommended to administer DAPT (aspirin + clopidogrel) periprocedurally and the triple therapy should be continued up to 1 month, irrespective of the stent type used. Prolonged triple therapy, up to 6 months, should be considered in ACS or in patients with otherwise high ischemic risk. In patients with high bleeding risk, dual therapy (OAT + clopidogrel) should be considered instead of 1-month triple therapy. After 12 months, discontinuation of DAPT should be considered and only OAC used.
- In patients with prior stent thrombosis, DAPT ≥12 months, and possibly as long as tolerated, should be considered, if stent thrombosis occurred while on adequate DAPT and if no mechanical stent-related causes could be detected.
- In patients with lower extremity artery disease and CAD, DAPT ≥12 months may be considered.
- In patients undergoing complex PCI, defined as the composite of ≥3 stents implanted, ≥3 lesions treated, bifurcation with two stents implanted, total stent length >60 mm, and chronic total occlusion (CTO) as target lesion, DAPT ≥6 months may be considered.
- In patients undergoing elective (non-cardiac) surgery, discontinuation of a P2Y12 inhibitor after 1 month should be considered (irrespective of the stent type and if Aspirin can be maintained throughout the perioperative period). However, in case of a recent MI or high ischemic risk, DAPT may be maintained and the surgery postponed for 6 months. If both Aspirin and a P2Y12 inhibitor need to be discontinued prematurely (and especially within the first month of stent implantation), bridging with intravenous antiplatelets may be considered. Ticagrelor should be stopped 3 days prior to surgery, clopidogrel 5 and prasugrel 7.
Bleeding management in patients on DAPT
As post-PCI bleeding is independently associated with mortality, the 2017 Focused Update on DAPT provides a summary of strategies to minimize the risk of bleeding episodes:
- Radial access is recommended over femoral, if performed by an experienced radial operator.
- Aspirin in the dose of 75-100mg is recommended on top of an P2Y12 agent.
- Proton pump inhibitors (PPI) are recommended in patients on DAPT, since gastrointestinal bleeding accounts for a big portion of bleeding complications.
- Routine platelet function testing is not recommended, due to it not being reliably associated with clinical outcomes.
Since no randomized evidence is available for cases of bleeding occuring while a patient is still on DAPT, practical recommendations are provided, which generally advise to keep the DAPT in case of minor, non-actionable bleedings. If blood loss results in Hemoglobin drop >3 g/dl, DAPT discontinuation is to be considered, albeit preferably keeping the P2Y12 inhibitor (single antiplatelet therapy), especially in case of upper GI bleeding. Naturally, in case of life-threatening bleeding, all antithrombotic therapy should be ceased.
The 2017 Focused Update on DAPT provides a comprehensive set of recommendations for the everyday use of DAPT after coronary stenting, with perhaps the underlying message being that an individual assessment of high bleeding (e.g. PRECISE-DAPT score ≥25) or ischemic risk (e.g. DAPT score ≥2 and/or complex PCI) may justify a shorter or longer DAPT duration, respectively, than the hitherto accepted standard of 6 months (clopidogrel) in stable or 12 months (ticagrelor or prasugrel) in ACS patients.