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Extended, standard, or De-escalation antiplatelet therapy for patients with coronary artery disease undergoing
Waqas Ullah1, Salman Zahid2, Harigopal Sandhyavenu3
1Division of Cardiology, Thomas Jefferson University Hospitals, 111 S 11th Street, Philadelphia, PA 19107, USA.
Insights
Dual antiplatelet therapy (DAPT) de-escalation strategies, particularly 3-month DAPT followed by P2Y12 inhibitor monotherapy, show comparable efficacy to standard 12-month DAPT for patients with coronary artery disease post-percutaneous coronary intervention, with a significant reduction in bleeding events.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Dual antiplatelet therapy (DAPT) duration and intensity are critical for balancing efficacy and safety in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
- The optimal DAPT strategy, including de-escalation, extended duration, and standard 12-month regimens, remains a subject of ongoing research and clinical debate.
Purpose of the Study:
- To compare the safety and efficacy of various DAPT de-escalation strategies against standard 12-month DAPT (DAPT-12) in patients with CAD post-PCI.
- To evaluate different DAPT regimens, including extended duration (ED), high-potency (HP), shorter duration (SD), and low-dose (LD) DAPT, through network meta-analysis.
Main Methods:
- A comprehensive search of online databases identified relevant randomized controlled trials (RCTs).
- A network meta-analysis (NMA) incorporating frequentist, bivariate, and influential methods was conducted on 30 RCTs involving 81,208 patients.
- Trial sequential analysis (TSA) was employed to assess the robustness of the findings.
Main Results:
- Compared to DAPT-12, de-escalation, HP-DAPT-12, and ED-DAPT strategies showed no statistically significant differences in major adverse cardiovascular events (MACE), stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), or all-cause mortality at 1-year follow-up.
- DAPT for 3 months followed by P2Y12-inhibitor monotherapy demonstrated a significantly lower incidence of major bleeding (RR 0.62), while HP-DAPT for 12 months showed a higher risk (RR 1.55).
- Net clinical benefit analyses favored 3-month DAPT followed by P2Y12-inhibitor monotherapy and discouraged HP-DAPT-12 and ED-DAPT.
Conclusions:
- DAPT for three months followed by P2Y12-inhibitor monotherapy, or aspirin plus clopidogrel after a short period of high-potency DAPT, appears to be a safe strategy post-PCI.
- While de-escalation strategies show promise, particularly in reducing bleeding, further validation through large-scale RCTs is necessary due to methodological limitations and the inclusion of a limited number of trials for novel approaches.
Aims:
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 And Results:
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. 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 favoured 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 favouring de-escalation strategy.
Conclusion:
DAPT for three 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.
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