Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior...

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Ticagrelor demonstrated a 15-16% reduction in major adverse cardiovascular events (MACE) in patients with prior myocardial infarction (MI) in the PEGASUS-TIMI 54 trial.
• The study investigated whether patients recently discontinuing P2Y12 inhibitors, even years post-MI, are at increased risk for MACE and might benefit from continued or reinitiated therapy.

Purpose of the Study:

• To evaluate the risk of MACE and the efficacy of ticagrelor based on the time elapsed since the last P2Y12 inhibitor discontinuation in patients with prior MI.
• To determine if patients who recently stopped P2Y12 inhibition derive greater benefit from ticagrelor therapy compared to those who discontinued it longer ago.

Main Methods:

• Patients from the PEGASUS-TIMI 54 trial were stratified by time since last P2Y12 inhibitor use (≤30 days, >30-360 days, >360 days).
• The risk of MACE and ticagrelor's efficacy were compared across these time categories using multivariable adjustment and interaction analyses.

Main Results:

• Patients who stopped P2Y12 inhibitors more recently (≤30 days) exhibited a significantly higher risk of MACE (HRadj 1.47) compared to those off therapy for over a year.
• Ticagrelor's benefit was significantly dependent on the time from last P2Y12 inhibitor dose, with greater efficacy observed in patients who stopped therapy more recently (P-trend for interaction < 0.001).
• The benefit of ticagrelor in patients ≤30 days post-discontinuation was consistent regardless of the time since MI (<2 years vs. ≥2 years).

Conclusions:

• The benefit of ticagrelor for long-term secondary prevention appears more pronounced in patients continuing or restarting therapy after a brief interruption of P2Y12 inhibition post-MI.
• These findings suggest that uninterrupted P2Y12 inhibitor therapy may offer greater benefit than reinitiating therapy after an extended period off medication for high-risk patients.
• Further research is needed to fully elucidate the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy.