RE-DUAL TICLO PCI: Dual Therapy with dabigatran/ticagrelor versus Dual Therapy with dabigatran/clopidogrel in ACS patients with indication for NOAC undergoing PCI.

Due to the increasing number of patients with atrial fibrillation undergoing
percutaneous coronary intervention (PCI), the optimal balance between
thromboembolic complications versus bleeding complications with the use of
anticoagulation and anti-platelet therapy has been investigated. Vitamin K
antagonist (VKA) seems to be omitted and novel oral anticoagulant (NOAC) is the
preferred choice, reducing bleeding risk and stroke. Especially in acute
coronary syndrome (ACS), real world data is missing. Subanalysis of studies
looking at ACS patients with NOAC undergoing PCI shows a trend toward lower
myocardial infarction rates in triple therapy (NOAC and dual antiplatelet
therapy), but the risk difference was less using full dose NOAC in dual therapy
(NOAC and single platelet therapy with P2Y12-inhibitor). In ACS the risk for
thromboembolic events and ischemia is the highest and the need for stronger
anti-platelet therapy to reduce this risk has to be investigated, especially
considering the proportion of patients who are non-responders to clopidogrel.
The most recent NSTEMI guideline of the European Society of Cardiology
downgraded triple therapy and set dual therapy with clopidogrel as default
therapy (EHJ 2020). However dual therapy with ticagrelor is recommended in
patients at high thrombotic risk (class 2b, level of evidence B. Therefore it
is really needed to compare ticagrelor to clopidogrel in patients with an
indication for NOAC and undergoing PCI for ACS .

This study has been transitioned to CTIS with ID 2024-518666-27-00 check the CTIS register for the current data.

A real world registry to compare dual therapy with Dabigatran/Ticagrelor to
dual therapie with Dabigatran/Clopidogrel in patients with an indication for
NOAC undergoing PCI in the setting of ACS. Hypothesis: Dual therapy with
Dabigatran/Ticagrelor will be non-inferior in reducing the risk of bleeding
compared to Dual therapy with Dabigatran/Clopidogrel (RE-DUAL PCI trial based)
in patients with an indication for NOAC undergoing PCI in the setting of ACS.
Thromboembolic events, stent thrombosis and death will be evaluated for
estimation of events between both groups. Data will be pooled for this
secondary endpoint with data from the upcoming WOEST-3 trial to compare both
treatments.

Open-label, multicenter, Regisry based Randomised controlled trial (RBRCT).

Intervention and controls
Patients in the intervention group will receive Dual therapy (REDUAL like):
Dabigatran and Ticagrelor. Patients can be assigned to two treatments:
• < 80 years: Dabigatran 150 mg twice daily and Ticagrelor 90 mg twice daily.
• >= 80 years or GFR 30-50 ml/min: Dabigatran 110 mg twice daily and Ticagrelor
90 mg twice daily.
• Contra-indication for Dabigatran is GFR < 30 ml/min.

Patients in the control group will receive Dual therapy with Dabigatran and
Clopidogrel:
• < 80 years: Dabigatran 150 mg twice daily and Clopidogrel 75 mg once daily.
• >= 80 years or GFR 30-50 ml/min: Dabigatran 110 mg twice daily and Clopidogrel
75 mg once daily.
• Contra-indication for Dabigatran is GFR < 30 ml/min.

Treatment with different NOACs
In order to replicate a population that closely reflects daily practice, it is
allowed to treat patients with different NOACs apart from Dabigatran. However,
Dabigatran remains the NOAC of first choice if possible. The use of other NOACs
with regards to renal function and comedication is described below, according
to Farmacotherapeutisch Kompas.

Edoxaban
In patients with Edoxaban, dose reduction is advised in patients with reduced
glomerular filtration rate. Age based dose reduction is not indicated for
Edoxaban.
GFR >50ml/min: Edoxaban 60mg once daily
GFR 15-50 ml/min: Edoxaban should be reduced to 30mg once daily.
When GFR < 15 ml/min, Edoxaban is contraindicated.

Furthermore, dose reduction of Edoxaban to 30mg once per day should be done in
the following conditions:
Body weight <= 60kg
Comedication with cyclosporines, erythromycin or ketoconazole
Apixaban
In patients with Apixaban dose reduction should be considered as follows:

GFR >= 30ml/min: Apixaban 5mg twice daily
GFR 15-29ml/min: Apixaban 2.5mg twice daily
GFR <15ml/min: contraindication for the use of Apixaban

Furthermore, dose reduction of Apixaban to 2.5mg twice per day, should be
considered in the following conditions:
Age >= 80 years
Body weight <= 60kg
Creatinine level of >= 133mmol/L

In mild liver dysfunction with Child-Pugh score 5-9, dose reduction is not
necessary. Use of Apixaban in severe liver dysfunction is contraindicated.
Rivaroxaban
Dose reduction of rivaroxaban should be considered in the following cases:
GFR >=50ml/min: Rivaroxaban 20mg once daily
GFR 15-49 ml/min: Rivaroxaban should be reduced to 15mg once daily.
When GFR < 15 ml/min, Rivaroxaban is contraindicated.

With regard to burden: I think the study is a little burden for patients with
regards to 2 short questionnaires. Rest is usual care. Possibly additionnal
information by telephone consultation. With regard to risks: Dual therapy is
already widely used in PCI patients, even in ACS patients the guideline has now
been adjusted to dual therapy. There are 2 antiplatelet agents available for
this and both are already used daily after PCI in ACS. Both have advantages and
disadvantages that are comparable, but this choice depends on the doctor and
the considerations per patient. This is a randomized setting to view if the
specific results of studies and from individual cases also showing the same
results in daily practice. We see in sub-analyzes that patients don't have
bigger risk compared to usual care, and both therapies are applied based on the
insight of (intervention) cardiologist and are individualized, which makes the
choice for the group in general more difficult. This study should provide a
shift towards a more uniform treatment.