A novel de-escalation antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention

Abstract

To investigate the effect of different DAPTs in patients with ACS undergoing PCI, and to identify the most efficient DAPT to reduce the risk of ischemia and bleeding after PCI. Between March 2017 and December 2021, 1598 patients with ACS who underwent PCI were included in the study. The DAPT protocol included the clopidogrel group (aspirin 100 mg + clopidogrel 75 mg), ticagrelor group (aspirin 100 mg + ticagrelor 90 mg), de-escalation Group 1 (reduced dose of ticagrelor [from 90 mg to 60 mg]) after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]), and de-escalation Group 2 (switched from ticagrelor to clopidogrel after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]). All patients received a 12-month follow-up. The primary endpoint was net adverse clinical events (NACEs) that included the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, stroke, and bleeding events. There were 2 secondary endpoints, major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding. No statistically significant difference was found in the incidence of NACEs between the 4 groups at the average 12-month follow-up (15.7% vs 19.2% vs 16.7% vs 20.4%). Cox regression analysis revealed that DAPT ticagrelor group regimen (hazard ratio [HR] 0.547; 95% confidence interval [CI]: 0.334-0.896; P = .017) were associated with a lower risk of MACCEs. Age (HR 1.024; 95% CI: 1.003-1.046; P = .022). DAPT de-escalation Group 2 regimen (HR 1.665; 95% CI: 1.001-2.767; P = .049) were marginally associated with a higher risk of MACCEs. Ticagrelor group regimen (HR 1.856; 95% CI: 1.376-2.504; P < .001) was associated with higher risk of bleeding events. Ticagrelor group regimen (HR 1.606; 95% CI: 1.179-2.187; P = .003) were associated with a higher risk of minor bleeding events. For patients with ACS underwent PCI, there were no significant difference in the incidence of NACEs between 3 and 12 months after PCI between de-escalation and non-de-escalation therapies. Compared with ticagrelor-based 12-month DAPT, there was no significant difference in MACCEs and bleeding events in patients receiving de-escalation treatment (ticagrelor reduction from 90 to 60 mg, 3 months after PCI).

Figure 1.

Clopidogrel group: aspirin + clopidogrel (12 months). Ticagrelor group: aspirin + ticagrelor 90 mg (12 months). De-escalation Group 1: from aspirin + ticagrelor 90 mg (3 months) to aspirin + ticagrelor 60 mg (9 months). De-escalation Group 2: from aspirin + ticagrelor 90 mg (3 months) to aspirin + clopidogrel (9 months). ACS = acute coronary syndrome, C = clopidogrel, CAD = coronary artery disease, DAPT = dual antiplatelet therapy, PCI = percutaneous coronary intervention, T = ticagrelor.

Figure 2.

(A) NACEs cumulative incidence. NACEs include the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, stroke, and bleeding events. cutoff point: 3rd month after PCI. (B) MACCEs cumulative incidence. MACCEs include the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. cutoff point: 3rd month after PCI. (C) Bleeding event cumulative incidence, including TIMI major bleeding and minor bleeding. A major bleeding event is defined as fatal hemorrhage, intracranial hemorrhage, or gastrointestinal hemorrhage requiring blood transfusion; a minor bleeding event is defined as epistaxis, gingival bleeding, bulbar conjunctival bleeding, skin ecchymosis, hematuria, or positive occult blood in stool, none of which require treatment by blood transfusion. cutoff point: 3rd month after PCI. (D) Major bleeding event cumulative incidence. A major bleeding event is defined as fatal hemorrhage, intracranial hemorrhage, or gastrointestinal hemorrhage requiring blood transfusion. cutoff point: 3rd month after PCI. Figure 2(e) Minor bleeding event cumulative incidence. A minor bleeding event is defined as epistaxis, gingival bleeding, bulbar conjunctival bleeding, skin ecchymosis, hematuria, or positive occult blood in stool, none of which require treatment by blood transfusion. cutoff point: 3rd month after PCI. MACCEs = major adverse cardiovascular and cerebrovascular events, NACEs = net adverse clinical events, PCI = percutaneous coronary intervention, TIMI = thrombolysis in myocardial infarction.

Figure 3.

(A) Hazard ratio for MACCEs. (B) Hazard ratio for bleeding events. (C) Hazard ratio for minor bleeding events. CI = confidence intervals, HR = hazard ratio, MACCEs = major adverse cardiovascular and cerebrovascular events.