Dual antiplatelet therapy discontinuation causes more thrombotic events at 12 months

Several randomized studies have shown that dual antiplatelet therapy (DAPT) is as effective to prevent thrombotic events in the segment treated with PCI, as it is with the rest of the coronary segments.

This is very clear. The problem is there are a series of adverse events following P2Y12 inhibitor discontinuation. This phenomenon called rebound effect, happens relatively soon after DAPT discontinuation.

In the DAPT study, comparing 30 day DAPT vs. 12 months DAPT in patients undergoing PCI, we observed there is a higher risk of thrombotic events within the first 3 months after discontinuation in both arms,  even though patients randomized to 12 month DAPT presented more events after discontinuation than those randomized to 30 day DAPT.

The PEGASUS-TIMI 54 looked into secondary prevention but reached similar conclusions, which is why we tend to think that after receiving more than 12 months DAPT we might be far more exposed to this rebound effect than we would with a shorter scheme.

Read also: “Dual Antiplatelet in TAVR: Is Single Better?”

This study analyzed 11473 patients from 6 randomized studies comparing a short DAPT scheme (3 to 6 months) vs. a long scheme (12+ months).

During the 90 days after clopidogrel discontinuation, there was no significant increase of thrombotic events between patients under the short and long schemes (HR: 1.18; CI 95%: 0.71 to 1.98; p=0.52; absolute difference in risk 0.10%).

The risk of infarction or stent thrombosis was similar between both treatment arms (HR: 0.93; CI 95%: 0.46 to 1.90; p=0.85).

Read also: “Post DES Dual Antiplatelet Therapy Still under Debate”.

A meta analyzis including 11 studies and nearly 39000 patients found out a higher risk of early events after discontinuation in patients under a 12+ scheme (HR: 2.28; CI 95%: 1.69 to 3.09; p<0.001), but not with a shorter 12 months scheme (HR: 1.08; CI 95%: 0.67 to 1.74; p for interaction=0.036).

Conclusion

In patients undergoing new generation DES stenting (more than 90%), clopidogrel discontinuation after 3 to 6 months was not associated to event increase within 90 days after discontinuation. However, the rebound effect was observed in patients receiving DAPT for more than 12 months.

Editorial Comment

The physiopathological hypothesis underlying the rebound effect in patients under a prolonged DAPT scheme is that chronic inhibition of P2Y12 inhibitors could lead to biological adaptation to platelet triggers and megakaryocytes that would lead to higher sensitivity to physiological ADP levels and other stimuli in the coagulation cascade.

Original Title Risk of Early Adverse Events after Clopidogrel Discontinuation in Patients Undergoing Short-Term Dual Antiplatelet Therapy.

Reference: Raffaele Piccolo et al. J Am Coll Cardiol Intv 2017;10:1621–30.

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