Influence of early dose reduction of ticagrelor on clinical outcomes following percutaneous coronary intervention for complex lesions

Abstract

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

Figure 1

Schematic description of the patient selection process. Among the 977 patients included in the study, 208 switched their DAPT regimens to those other than ticagrelor-based DAPT before 6 months of follow-up, 115 changed to low-dose ticagrelor-based DAPT and 657 remained on standard-dose ticagrelor-based DAPT at 6 months of follow-up. The median duration of standard-dose ticagrelor use was 179 (IQR, 99–198) days in the low-dose group and 371 (IQR, 347–404) days in the standard-dose group (p < 0.001).

Figure 2

DAPT regimen change patterns within 6 months. Among the 977 patients included in the study, 32.8% switched to regimens other than standard-dose ticagrelor-based DAPT, and the 2 most common regimens to change were prasugrel-based DAPT and low-dose ticargrelor-based DAPT. The 3 most common reasons for the regimen changes were physician preference, respiratory adverse events and bleeding. Physician preference was more frequent in the ticagrelor-based DAPT group, while respiratory adverse events were more frequent in the nonticagrelor-based DAPT group. SAPT, single antiplatelet agent therapy; DAPT, dual antiplatelet therapy.

Figure 3

Kaplan‒Meier survival analysis for MACEs, bleeding events and NACEs in the IPTW-applied cohort. The cumulative incidences of all clinical events were not significantly different between the standard-dose and low dose groups (A). Landmark analyses also showed that the cumulative incidences of all clinical events were not significantly different beyond 6 months after PCI (B). MACE, major adverse cardiovascular event; NACE, net adverse clinical event; PCI, percutaneous coronary intervention; DAPT, dual antiplatelet agent.

Figure 4

Time-varying survival curves of MACEs, bleeding events, and NACEs. A switching to low-dose ticagrelor-based DAPT occurred in 130 patients throughout the follow-up. A time-varying survival analysis showed that the cumulative incidences of MACE and NACE were not different between the standard-dose and low-dose groups, but bleeding was marginally more frequent in the low-dose group. MACE, major adverse cardiovascular event; NACE, net adverse clinical event; PCI, percutaneous coronary intervention.