Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with ACS: a meta-analysis

Abstract

Abstract Background Dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor is recommended in patients with acute coronary syndrome (ACS) and should be tailored according to ischemic and bleeding risks, which are highest in the acute phase, and gradually attenuate overtime. De-escalation strategies of DAPT aim to optimize this balance of risks. Purpose We compared guided or unguided DAPT de-escalation strategies from potent P2Y12 inhibitors to either clopidogrel or lower doses of potent P2Y12 inhibitors versus standard DAPT with potent P2Y12 inhibitors among patients with ACS. Methods PubMed, Google Scholar and Cochrane Central Register of Controlled Trials were searched from inception till March 10th 2021. 1633 records were screened on DAPT de-escalation strategies after ACS for inclusion. Aspirin monotherapy and non-randomized trials were excluded. The primary endpoint was BARC ≥2 bleeding. Other endpoints included MACE (defined according to the definitions reported in the original study protocols), all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, and stroke. Hazard ratios (HRs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Heterogeneity was assessed with the I2 index. We assessed the interaction between de-escalation strategy (guided vs. unguided) and treatment with a random-effects meta-regression analysis with the empirical Bayes method. This study has been submitted to PROSPERO for registration. Preliminary findings Four randomised trials and a total of 8,082 patients randomly allocated to a de-escalation strategy (genetic guided to clopidogrel, n=1,242; platelet function guided to clopidogrel, n=1,304; unguided to clopidogrel (n=323); unguided to lower dose, n=1,170) or standard DAPT (n=4,043) were included in our analysis. De-escalation strategy had a reduction in BARC ≥2 bleeding (HR 0.57, 95% CI 0.37–0.89; I2=81%). MACE (HR 0.79, 95% CI 0.62–1.02; I2=0%), all-cause death (HR 0.89, 95% CI 0.58–1.36), cardiovascular death (HR 0.63, 95% CI 0.36–1.10; I2=0%), myocardial infarction (HR 0.81, 95% CI 0.56–1.17; I2=0%), stent thrombosis (HR 0.57, 95% CI 0.19–1.74; I2=0%) and stroke (HR 0.73, 95% CI 0.39–1.35; I2=0%) did not differ between patients with a de-escalation strategy and those without. Meta-regression analysis did not show any significant interaction between de-escalation method (guided vs. unguided) and treatment effects, except for BARC ≥2 bleeding (P interaction = 0.070), suggesting a greater reduction with unguided de-escalation. Conclusion A de-escalation strategy of DAPT after ACS was associated with a lower number of clinically relevant bleeding events, mostly in patients who underwent unguided de-escalation, while no association with increased ischemic events was found. However, the observed broad confidence intervals limit the certainty of our findings. Funding Acknowledgement Type of funding sources: None. BARC ≥2 bleedingMACE