DAPT de-escalation vs standard DAPT

Guided and unguided de-escalation from potent P2Y12 inhibitors in acute coronary syndrome patients: A systematic review and meta-analysis.

Findings from this meta-analysis may lead physicians to consider dual antiplatelet therapy (DAPT) de-escalation as a reasonable strategy to reduce the bleeding risk in acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI) and completed an initial DAPT period, without any apparent increased ischemic risk.

Key Takeaway

• DAPT de-escalation after PCI for ACS, either unguided or guided by genetic or platelet function testing (PFT), reduced clinically relevant bleeding and major adverse cardiovascular events (MACE) compared with standard DAPT with potent P2Y12 inhibitors.
• Unguided vs guided DAPT de-escalation showed a greater reduction in bleeding risk and a similar reduction in risk of ischemic events.

Why This Matters

• Guidelines recommend DAPT with aspirin and a potent P2Y12 inhibitor (i.e., prasugrel or ticagrelor) for 12 months after ACS.
• However, the ischemic risk attenuates over time after the acute phase and the bleeding risk remains elevated during follow-up in these patients.
• De-escalation strategies (switching from a full-dose potent to a reduced-dose or less potent P2Y12 inhibitor) may continue the ischemic protection while decreasing the long-term bleeding risks after an initial phase of DAPT with a potent P2Y12 inhibitor.

Study Design

• This systematic review and meta-analysis included randomized controlled trials (RCTs) that enrolled patients with ACS who underwent PCI and were allocated to DAPT de-escalation vs standard DAPT with a potent P2Y12 inhibitor.
  • Eligible RCTs were searched using PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials.
• De-escalation was defined as a strategy of dose reduction of a potent P2Y12 inhibitor or switching from potent P2Y12 inhibitor to clopidogrel with or without genetic or PFT guidance (after an initial period of DAPT).
• Exclusion criteria: Observational studies, registry data, ongoing trials without results, editorials, aspirin monotherapy trials, and duplicate studies
• Primary endpoint: Clinically relevant bleeding (Bleeding Academic Research Consortium [BARC] ≥2 bleeding) at 12 months of follow-up
• Other endpoints: Trial-defined MACE, all-cause and cardiovascular mortality, myocardial infarction (MI), stent thrombosis, stroke, and major bleeding at 12 months of follow-up

Key Results

• Overall, five randomized trials (N = 10,779 patients) that allocated patients to 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) vs standard DAPT, n = 5,391) were included.
• Bleeding events: DAPT de-escalation significantly reduced BARC ≥2 bleeding compared with standard DAPT (hazard ratio [HR] = 0.57; 95% confidence interval [CI]: 0.42–0.78; I² = 77%; number of patients needed to treat [NNT] = 33)
  • Both unguided (HR = 0.44; 95% CI: 0.32–0.59; I² = 34%) and guided de-escalation (HR = 0.79; 95% CI: 0.66–0.94; I² = 0%) strategies showed consistent results.
• Both de-escalation types had concordant reductions in bleeding events compared with standard DAPT:
  • De-escalation to clopidogrel: HR = 0.59; 95% CI: 0.41–0.85; I² = 80%
  • De-escalation to reduced dose of prasugrel: HR = 0.48; 95% CI: 0.32–0.72)
• The rate of major bleeding was similar between de-escalation and standard DAPT groups (HR = 0.83; 95% CI: 0.56–1.24; I² = 28%).
• Significant interaction was found between the de-escalation method (guided vs unguided) and BARC ≥2 bleeding (Pinteraction = 0.037), suggesting a greater reduction with unguided de-escalation than guided de-escalation.
• Ischemic events: DAPT de-escalation vs standard DAPT reduced MACE risk (HR = 0.77; 95% CI: 0.62–0.96; I² = 0%; NNT = 97)
  • Both guided (HR = 0.80; 95% CI: 0.58–1.11) and unguided de-escalation (HR = 0.75; 95% CI: 0.55–1.01) strategies showed consistent results.
• No interaction was observed between the de-escalation method (guided vs unguided) or the de-escalation type (to clopidogrel vs to lower dose of prasugrel) and MACE (Pinteraction = 0.79 and 0.96, respectively).
• The risk of all-cause mortality, cardiovascular mortality, MI, stent thrombosis, and stroke was not significantly different between DAPT de-escalation vs standard DAPT.

Limitations

• This meta-analysis was not performed on individual patient-level data.
• The study restricted the analysis to RCTs, which may limit the generalizability of the results.
• Heterogeneity was high between studies for the bleeding outcome and was not observed for ischemic outcomes.
• The plurality of de-escalation methods might render this result difficult to implement without additional, more specific studies.
• In all trials reviewed, only 21 events of stent thrombosis without data on timing after the index event were reported

MAT-BH-2300027/v1/Jan2023