Risk of early adverse events after Clopidogrel discontinuation in patients undergoing short-term Dual Antiplatelet Therapy: An individual participant data analysis
Selected in JACC: Cardiovascular Interventions by G. Di Gioia
Piccolo R, Feres F, Abizaid A, Gilard M, Morice MC, Hong MK, Kim HS, Colombo A, Bhatt DL, Palmerini T, Stone GW, Windecker S, Valgimigli M
JACC Cardiovasc Interv. 2017 Aug 28;10(16):1621-1630
LinkRead the abstract
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Why this study – the rationale/objective?
During the last few years it has been suggested that there might be a rebound effect of P2Y12 inhibitors, leading to an increase in adverse ischemic events early after discontinuation. On the other hand, the safety of early discontinuation of DAPT is still a matter of debate.
How was it executed – the methodology?
Individual patient data was gathered for 11.473 patients from 6 randomized trials comparing short (3-6 months) to long (at least 12 months) duration of DAPT after PCI performed using predominantly second generation drug-eluting stents.
An additional meta-analysis was performed in nearly 35.000 patients from 11 studies in which individual patient data was not available.
Primary endpoint was MACCE (major adverse cardiovascular and cerebrovascular events).
What is the main result?
In the individual patient data analysis, shorter duration of anti platelet therapy (3-6 months) did not show a higher risk of adverse events during the first 90 days after discontinuation as compared to the long DAPT duration (at least 12 months).
In the systematic review and meta-analysis there was a significant interaction between DAPT duration before discontinuation and outcomes after therapy withdrawal, with a higher risk of MACCE in the first 90 days after DAPT cessation in trials where DAPT was stopped at or after 1 year but not in those mandating shorter treatment duration.
Critical reading and the relevance for clinical practice
This study further corroborates, in a large number of patients, the safety of early discontinuation of dual antiplatelet therapy in patients with stable angina undergoing PCI with second generation drug-eluting stents. Moreover, it points out that prolonged DAPT duration, which seems to be beneficial in acute coronary syndromes in patients with low hemorrhagic risk, might not be completely harmless in patients with stable angina. Actually, there could be a rebound effect after P2Y12 withdrawal, possibly related to the DAPT exposure time, since it was not seen after discontinuation of short-term DAPT.
These findings, though, are only speculative for the many limitations of this study, some of which are related to the study design and its post-hoc nature. Furthermore, only stable angina or low risk ACS were included; Clopidogrel was the only P2Y12 inhibitor to be used; many studies included had an open label design with a possible allocation bias.