Extended, standard, or De-escalation antiplatelet therapy for patients with coronary artery disease undergoing percutaneous coronary intervention? A trial-sequential, bivariate, influential, and network meta-analysis

Abstract

Background The relative safety and efficacy of de-escalation, extended duration (ED) (>12-months) and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. Methods Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. Results A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12 and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR) and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45–0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16–2.06). The net clinical benefit and rankograms also favored DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favoring de-escalation strategy. Conclusion DAPT for 3 months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

Abatement of potent P2Y12 antagonist-based dual antiplatelet therapy after coronary intervention: A network meta-analysis of randomized controlled trials

“…Our analysis also enabled comparison of the two strategies. Our results align with the outcomes of the recent meta-analyses by Laudani et al ( 28 ) and Ullah et al ( 29 ), where P2Y12 inhibitor de-escalation decreased ischemic risk, and P2Y12 inhibitor monotherapy decreased bleeding.…”

Very Short Versus Longer Dual Antiplatelet Treatment After Coronary Interventions: A Systematic Review and Meta-analysis

“…Ticagrelor has been considered an acceptable option after short-term DAPT [ 27 ]. In their recent network meta-analysis, Ullah et al showed that 3 months of DAPT followed by ticagrelor monotherapy was associated with the best outcomes, independently of the indication of the procedure [ 28 ]. However, more studies comparing ticagrelor with aspirin and another P2Y12 inhibitor as monotherapy after a short course of DAPT are required.…”

“…1 Forest plot demonstrating the effect of very short-term versus > 3 months of DAPT on net adverse clinical events, with odds ratios and 95% CIs. CI confidence interval, DAPT dual antiplatelet therapy, M-H Mantel-Haenszel, df degrees of freedom [28]. However, more studies comparing ticagrelor with aspirin and another P2Y12 inhibitor as monotherapy after a short course of DAPT are required.…”

Antiplatelet Therapy Aims and Strategies in Asian Patients with Acute Coronary Syndrome or Stable Coronary Artery Disease

“…Large-scale studies comparing APT strategies would be challenging to conduct, but highly informative. A recent metaanalysis of 30 extended, standard, and de-escalation APT RCTs supported the safety of two strategies: 3-month DAPT followed by ticagrelor monotherapy, as well as a short period of high potency DAPT followed by clopidogrel + aspirin [108]. Another meta-analysis of seven de-escalation trials favored early de-escalation of DAPT after 1 to 3 months to P2Y1 2 i monotherapy [109].…”