Unguided De-escalation Effective in DAPT for STEMI or Acute Coronary Syndromes

The most effective dual antiplatelet therapy (DAPT) strategy for ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndromes (NSTE-ACS) may be unguided de-escalation, according to findings published in the International Journal of Cardiology.

Investigators sought to determine the most effective DAPT strategies for STEMI and NSTE-ACS. Net adverse clinical events (NACE) (composite of major adverse cardiovascular events [MACE] and relevant bleeding events) was the primary outcome.

The systematic review and meta-analysis was conducted via a search of Cochrane CENTRAL, EMBASE, and PubMed databases from inception to February 2023 for randomized controlled trials (RCTs) on DAPT strategies. The investigators found 20 RCTs that included STEMI patients (n=24,745) or NSTE-ACS patients (n=37,891) receiving standard DAPT (12 months with clopidogrel or potent P2Y₁₂ inhibitors), short-term DAPT (≤6 months) then aspirin or potent P2Y₁₂ inhibitors, guided selection with platelet or genotype function tests, and unguided de-escalation from potent P2Y₁₂ inhibitors to clopidogrel or low-dose potent P2Y₁₂ inhibitors at 1 month.

Included RCTs reported on NACE, but studies with less than 90% of patients with ACS, DAPT duration greater than 18 months, or DAPT with cilostazol were excluded. All included studies had low risk of bias (Cochrane Collaboration risk of bias 2.0 tool), and there was no publication bias for any of the assessed outcomes.

Compared with standard DAPT using potent P2Y₁₂ inhibitors in patients with STEMI, a lower rate of NACE was associated with unguided de-escalation strategy without increased risk of MACE (hazard ratio [HR], 0.57; 95% CI, 0.34-0.96; I²=65.3%).

Unguided de-escalation strategy in patients with NSTE-ACS had a lower rate of NACE without increased risk of MACE compared with standard DAPT using potent P2Y₁₂ inhibitors (HR, 0.62; 95% CI, 0.50-0.78), the guided selection strategy (HR, 0.65; 95% CI, 0.47-0.90), and standard DAPT using clopidogrel (HR, 0.73; 95% CI, 0.55-0.98).

Compared with standard DAPT with P2Y₁₂ inhibitors, short DAPT followed by P2Y₁₂ inhibitors was associated with a lower rate of NACE (HR, 0.69; 95% CI, 0.48-0.99; I²=0%).

No significant differences were found between the DAPT strategies for MACE in STEMI, with moderate heterogeneity (I²=39.3%). Compared with unguided de-escalation strategy, standard DAPT with potent P2Y₁₂ inhibitors, and standard DAPT with clopidogrel in patients with STEMI, short DAPT followed by P2Y₁₂ was associated with a lower rate of major bleeding, with moderate heterogeneity (I²=25.8%).

No significant differences were found between DAPT strategies for MACE in NSTE-ACS, with high heterogeneity (I²=50.3%). Compared with standard DAPT with potent P2Y₁₂ inhibitors, standard DAPT with clopidogrel was associated with a lower rate of major bleeding, with high heterogeneity (I²=56.7%).

Some limitations of the study include the design, the potential influence of confounding factors, and differing definitions across trials.

“Unguided de-escalation strategy was associated with a reduced risk of NACE and may be the most effective DAPT strategy for STEMI and NSTE-ACS,” the investigators wrote. “…our results suggest that the risk of MACE is not increased with any of the DAPT strategies in STEMI patients, and that the risk of bleeding may be less with the short DAPT followed by potent P2Y12 inhibitors strategy compared with standard DAPT with potent P2Y12 inhibitors.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.