Andrei Mesina: Tailoring Post-PCI Antithrombotic Therapy Balances Bleeding and Ischaemic Risks
Andrei Mesina, Resident Doctor at Schleswig-Holstein University Medical Center, shared a post on LinkedIn about a recent article by Konstantinos D. Rizas et al., published in Nature Medicine, adding:
“More intensive antithrombotic therapy is not always better – but less therapy is not always enough either.
Two important trials presented at ESC Congress 2026 highlight the delicate balance between ischaemic protection and bleeding risk after PCI.
Epidaurus
In 602 patients with atrial fibrillation and recent ACS, a one-month regimen of a DOAC plus a potent P2Y12 inhibitor – ticagrelor or prasugrel – was compared with a DOAC plus clopidogrel and in-hospital aspirin.
The trial was stopped prematurely because of safety concerns:
- Potent P2Y12 inhibition produced no clear reduction in ischaemic events.
- BARC ≥3 bleeding was more than threefold higher (HR 3.54).
- The results therefore reinforce clopidogrel as the preferred P2Y12 inhibitor for most patients with AF and ACS requiring oral anticoagulation.
A-CLOSE
This trial addressed a different clinical scenario: 3,203 high-ischaemic-risk patients who had already remained event-free for 12 months after drug-eluting stent implantation.
Clopidogrel monotherapy was compared with extended DAPT using clopidogrel plus aspirin:
- Net adverse clinical events were similar: 5.0% vs. 5.1%.
- Clopidogrel monotherapy reduced BARC 2, 3 or 5 bleeding: 1.8% vs. 4.1%.
- However, extended DAPT provided greater ischaemic protection: 1.6% vs. 3.7%.
How should we interpret these trials together?
They are complementary – not contradictory.
Epidaurus suggests that escalating from clopidogrel to ticagrelor or prasugrel in patients already receiving a DOAC adds bleeding without proven ischaemic benefit.
A-CLOSE shows that, in high-ischaemic-risk patients without an anticoagulation indication, continuing aspirin alongside clopidogrel may prevent more ischaemic events – but at the cost of substantially more bleeding.
The key message is therefore not simply ‘more’ or ‘less’ antithrombotic therapy.
It is the right intensity for the right patient at the right time.
Our decisions must remain individualized according to:
- Bleeding risk
- Ischaemic and anatomical complexity
- Requirement for oral anticoagulation
- Time elapsed since ACS or PCI
- Patient preferences and shared decision-making
How will these results influence your antithrombotic strategy after PCI?”
Title: Dual antithrombotic therapy using potent antiplatelet inhibitors in atrial fibrillation and acute coronary syndrome: a randomized controlled trial
Authors: Konstantinos D. Rizas, Konstantinos Mourouzis, Dominik Rath, Christoph B. Olivier, Laura Elisa Villegas Sierra, Theofanis Korovesis, Amin Polzin, Amani Al Tawil, Reza Wakili, Lukas von Stuelpnagel, Katharina Mayer, Marion Janisch, Tanja Ulrich, Sarah Lang, Sebastian K. G. Maier, Florian Brattinger, Lorenz Bott-Flügel, Harilaos Bogossian, Konstantinos Iliodromitis, Luisa Freyer, Julius Steffen, Konstantin Stark, Elodie Eiffener, Lauren E. Sams, Tobias Petzold, Axel Linke, Felix M. Heidrich, Samuel Sossala, Saif Zako, Nikolaos Dagkonakis, Andreas Schäfer, Frank Edelmann, David M. Leistner, Mariya Maslarska, Fabian Knebel, Georg Nickenig, Blerim Luani, Tienush Rassaf, Hüseyin Ince, Ibrahim Akin, Micha T. Maeder, Meinrad Gawaz, Hans-Josef Feistritzer, Norbert Frey, Stefan Kääb, Riza Sahin, Matthias Pauschinger, Thomas Stiermaier, Ingo Eitel, Marc Kollum, Jan Sebastian Wolter, Michael Schreinlechner, Axel Bauer, Christoph Stellbrink, Ulf Landmesser, Paulus Kirchhof, Dirk Sibbing, Holger Thiele, Adnan Kastrati, Ulrich Mansmann, Steffen Massberg
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