Summary

Optimal anti-thrombotic therapy in AF patients who have had PCI comprises of striking a balance between 3 major concerns- cardiac, stroke, and bleeding. Here, Prof. Dr. Sundeep Mishra provides guidance on which therapy to choose based on consensus recommendations and reports from recent trials.

The management of patients who have undergone percutaneous coronary intervention (PCI) and already have atrial fibrillation (AF) is a challenging but a common problem. Broadly there are three issues in the management paradigm;

• risk of stent thrombosis (ST) post-stent implantation
• risk of ischemic stroke due to emboliztion of clot (formed commonly in left atrial appendage) as a result of irregular rate alterations in AF
• risk of bleeding consequent to use of anti-platelets / anticoagulants

Since anti-platelet drugs have some anti-coagulant effect and anti-coagulant drugs have some anti-platelet effects, theoretically it might be reasonable to assume that using one class of drug may be sufficient for both activities. However, it has to be understood that anti-platelet drugs act predominantly in reducing arterial thrombosis (consequent upon PCI) whereas anti-coagulants are predominantly effective in reducing venous thrombosis (precursor of stroke and TE complications of AF). The effect of one therapeutic modality on the other one is very weak at best. It is thus clear that a combination of both agents would be required to appropriately address risk of this complex situation.

Indeed early guidelines suggested triple anti-thrombotic (TAT) strategy for patient of AF undergoing PCI with stent implantation. However, TAT, while vary efficacious for ischaemic and thrombo-embolic complications, carries a nearly 3 fold increase in risk of bleeding. Indeed several trials and later network meta-analysis revealed that risk of bleeding with TAT compared with any other strategy.

It is thus clear that a better combination will be required which will balance all the risks associated with arterial thrombosis, venous thrombosis and bleeding risks. A comparison of risk: benefit of individual drugs may aid selecting an appropriate therapy.

Anti-ischaemic risk benefit

The anti-ischaemic risk is as follows:

ASA< < Low dose VKA< NOACs < High dose VKA < Clopidogrel < Ticagrelor < Prasugrel < DAPT< TAT < Clopidogrel + Low dose NOAC < P2Y12 Inhibitor + High dose VKA < DAPT + Low dose NOAC

Anti-thrombo-embolic risk

The stroke risk and other thrombo-embolic risk is as follows:

ASA< Clopidogrel < Ticagrelor < Prasugrel < Low dose VKA < NOAC < Clopidogrel + Low dose NOAC < P2Y12 Inhibitor + High dose VKA < DAPT + Low dose NOAC < TAT

Bleeding risk

The bleeding risk is as follows:

ASA < NOAC < Low dose VKA < High dose VKA < Clopidogrel < Ticagrelor < Prasugrel < Clopidogrel + Low dose NOAC < P2Y12 Inhibitor + High dose VKA < DAPT + Low dose NOAC < TAT

While risk benefit profile of individual anti-platelet and anti-coagulant may be useful in predicting the profile of their combinations, there could be some variations. For example, while TAT should be possessing most efficacy, in reality their efficacy can be lower than a combination of DAPT and low dose NOAC. The reason could be that because of increased bleeding risk, during the time of bleeding, effective anti-thrombotic therapy may be discontinued contributing to increased ischaemic risk.

1. It is clear from the above discussion that DAPT has the least anti-thrombotic efficacy (and also low stroke efficacy) and TAT has the highest bleeding risk (at least 50% more than any dual combination).
2. As such both are not suitable for this complex subset. Full dose NOAC+ P2Y12 Inhibitor has a high bleeding risk as well (although this combination has the highest thrombotic efficacy).
3. Low Dose NOAC with DAPT has higher anti-thrombotic efficacy compared to VKA + P2Y12 Inhibitor but it has higher bleeding risk as well.

Tips and tricks for using anti-thrombotics

• Where NOAC is used along with clopidogrel or other P2Y12 inhibitors, a lower dose should be used
• In setting of ACS, dabigatran increases the risk of GI bleeding
• Rivaroxaban in very low doses (2.5 mg BD) possesses anti-ischemic properties although it may not be useful in stroke prevention at this dose
• NOACs are associated with significantly lower intra-cranial bleeding vs. VKA
• Newer P2Y12 inhibitors like prasugrel or ticagrelor should not be used with NOACs because of increased bleeding risk; there is especially a drug interaction between Dabigatran and Ticagrelor

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The writer, Dr. Sundeep Mishra is a Professor of Cardiology.