Following DAPT cessation, P2Y12 inhibitors better than aspirin for monotherapy, JACC analysis.

Over past few years, there has been upcoming literature supporting shorter duration DAPT regimens following PCI. But what remains unknown is which antiplatelet (aspirin or P2Y12 inhibitors) agent is better once switch from DAPT to single antiplatelet therapy (SAPT) is made.

In a recent network analysis published in JACC CI, authors Ando et al have found that P2Y12-I monotherapy following DAPT discontinuation after PCI is associated with a significantly lower risk for MI and similar risk for major bleeding, when compared to aspirin monotherapy.

Current clinical practice guidelines (CPGs) recommend DAPT durations of 6 months after PCI for chronic coronary syndromes (CCS) and 12 months for patients presenting with acute coronary syndromes (ACS) although shorter DAPT regimens have been advocated to high bleeding risk individuals.

Although precedent has established aspirin as the SAPT of choice following short DAPT, recent evidence supports P2Y12 inhibitor SAPT as preferable with respect to the balance of bleeding and ischemic events. To confirm this observation, Andò et al performed a network meta-analysis of 19 studies from which they compared aspirin vs P2Y12 inhibitor SAPT following DAPT after PCI.

Primary efficacy and safety endpoints were myocardial infarction (MI) and major bleeding (MB), respectively. Key findings include the following:

1) Aspirin SAPT was associated with a 32% increase in myocardial infarction (MI), an increase in stroke, and a similar risk for major bleeding compared with P2Y12 inhibitor SAPT;

2) Point estimates for stroke and stent thrombosis (ST) favor P2Y12 inhibitor SAPT;

3) P2Y12 inhibitor SAPT had the highest probability of ranking first for reduction in all adverse outcomes; and

(4) Both aspirin and P2Y12 inhibitor SAPT reduce bleeding compared with prolonged-duration DAPT.

Which P2Y12 agents is/are better?

"These data suggest that either aspirin or clopidogrel SAPT after short DAPT is suboptimal in an East Asian population undergoing PCI for ACS and that ticagrelor SAPT is preferable", notes Dean J. Kereiakes in an accompanying editorial. He further adds-" conversely, early after PCI for ACS, more potent and consistent P2Y12 inhibition using agents with less interindividual variability (ticagrelor or prasugrel) appears desirable."

Key takeaways:

The present analysis supports aspirin discontinuation at the transition from DAPT to SAPT, with provisions. First, the choice of P2Y12 inhibitor should take into account population risk for ischemic or bleeding events on the basis of prevalence of cytochrome P450 2C19 loss-of-function polymorphisms and the presenting clinical syndrome (ACS vs CCS).

Potency and consistency of platelet inhibition make ticagrelor or prasugrel standard of care for ACS and the optimal choice for SAPT after short DAPT in this population.

Second, among patients presenting with CCS or late (6-18 months) after PCI for ACS, clopidogrel SAPT appears sufficient.

Third, alternative therapies such as DAPT de-escalation to low-dose ticagrelor, low-dose prasugrel, or to clopidogrel, in combination with aspirin reduces bleeding events with similar rates of ischemic events compared with CPG-recommended DAPT durations, and this strategy is preferable in populations with high ischemic risk.

Source: JACC CI

1. DOI: 10.1016/j.jcin.2022.08.009

2. DOI: 10.1016/j.jcin.2022.08.017