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

Abstract

Aim Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full dose potent P2Y12 inhibitors in ACS patients who underwent PCI. Methods & results PubMed, Google Scholar and Cochrane Central Register of Controlled Trials were searched for eligible randomised controlled trials. Aspirin monotherapy trials were excluded. Five randomised trials (n = 10,779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1,242; platelet function guided to clopidogrel n = 1,304; unguided to clopidogrel n = 1,672; unguided to lower dose n = 1,170) versus standard DAPT (control group n = 5,391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥ 2 bleeding (HR 0.57, 95% CI 0.42–0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis and stroke (HR 0.77, 95% CI 0.62–0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. Conclusion De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing, was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.

Comparison of Unguided De-Escalation Versus Guided Selection of Dual Antiplatelet Therapy After Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis

“…40 That study was significantly limited because it incompletely differentiated the 2 distinct de-escalation strategies with different timing of de-escalation by meta-regression analyses, and it did not thoroughly assess the critical question of whether the unguided de-escalation strategy is similarly effective and safe compared with the guided selection strategy. 40 Despite the limitation, the study concluded both the guided and unguided de-escalation strategies are safer than DAPT with potent P2Y 12 inhibitors. In contrast, our study performed indirect comparisons through network meta-analysis of the unguided de-escalation strategy and the guided selection strategy.…”

Percutaneous coronary intervention in the patient at high risk of bleeding

“…Although in theory the first alternative is more effective, a recent meta-analysis has suggested that both may be effective. 27 Despite the existence of studies specifically addressing this therapeutic alternative, it still does not have clear support for routine use, as the results of these clinical trials were not able to change clinical practice. 26 For example, the latest American guideline on myocardial revascularization does not include this alternative in the list of possibilities that may be considered to prevent bleeding complications, i.e., it is an alternative without a clearly defined role.…”

Unguided De-Escalation Strategy From Potent P2Y12 Inhibitors in Patients Presented With ACS: When, Whom and How?

“…A recent meta-analysis (5 randomized clinical trials [RCTs], n=10,779) showed that DAPT de-escalation (when: from in-hospital to 1 month post-PCI) vs. standard DAPT with full-dose potent P2Y 12 inhibitor was associated with a significant reduction in Bleeding Academic Research Consortium (BARC) ≥type 2 bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.42–0.78) as well as major adverse cardiac events, represented by the composite of CV mortality, myocardial infarction (MI), stent thrombosis, and stroke (HR, 0.77; 95% CI, 0.62–0.96) in ACS patients who underwent PCI. 3) Although the consistency was noted across various de-escalation strategies, it cannot guarantee that this strategy can be applied globally because of its limited power and sample size. 3) …”

“… 3) Although the consistency was noted across various de-escalation strategies, it cannot guarantee that this strategy can be applied globally because of its limited power and sample size. 3) …”

“…Another Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 in Patient with Acute Coronary Syndrome (STOP DAPT2-ACS) trial 7) enrolling Japanese ACS patients treated with less potent P2Y 12 inhibitor (i.e., clopidogrel or 3.75-mg prasugrel) (n=4,136) also showed that short DAPT strategy (P2Y 12 inhibitor monotherapy following 1-month DAPT) was associated with the increased risk of MI (1.59% vs. 0.85%) and stent thrombosis (0.45% vs. 0.20%), albeit at the benefit of a lower incidence of BARC 3 or 5 bleeding (0.54% vs. 1.31%). Contrary to de-escalation of P2Y 12 inhibitor, 3) early (≤1 month) aspirin discontinuation with clopidogrel monotherapy may increase the rate of ischemic events even in patients with low thrombotic risk (e.g., East Asian patients). 8) …”