Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management

Abstract

Background: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. Methods: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. Results: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P =0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P =0.04) and fatal bleeding (1% [4/400] vs 0%, P =0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P =0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. Conclusions: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02094963.

Real-World Bleeding and Ischemic Events in Asian Patients on P2Y12-Inhibitors After Percutaneous Coronary Intervention: A National Claims Data Analysis

“…Our results are consistent with those from the PHILO study conducted in East-Asian patients, which reported that the incidence of bleeding and cardiovascular events was higher in ticagrelor users than in clopidogrel users [16]. In comparison with clopidogrel, a recent randomized controlled trial in Korean patients with ACS also reported a higher risk of bleeding with ticagrelor but found no significant difference in cardiovascular death [24]. These observations are in line with the phenomenon referred to as the ''East Asian paradox,'' which describes the vulnerability to bleeding and resistance to ischemic events of East Asian populations compared with Caucasians [25].…”

Long-Term Safety and Efficacy of Extended Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Real-World Practice

“…However, East Asian patients with ACS undergoing PCI may be more likely to have bleeding events than Western patients with potent P2Y12 receptor inhibitors. [22][23][24] For this reason, more medical attention is required to maintain an extended duration of potent P2Y12 receptor inhibitor for East Asian patients with ACS who undergo PCI.…”

Adjunctive Cilostazol to Dual Antiplatelet Therapy to Enhance Mobilization of Endothelial Progenitor Cell in Patients with Acute Myocardial Infarction: A Randomized, Placebo-Controlled EPISODE Trial

“…Based on these results, pharmacological agents showing EPC-mobilizing effect (e.g., cilostazol or ticagrelor) may provide a therapeutic option to promote vascular repair and prevent thrombotic events after stent implantation. However, ticagrelor versus clopidogrel treatment significantly increased bleeding risk without a protective benefit against thrombotic events in Asian patients [18,19]. Considering the net clinical benefit without a trade-off of bleeding risk, triple antiplatelet therapy with cilostazol, clopidogrel, and aspirin may be a plausible regimen in ACS patients at high-bleeding risk (e.g., East Asians, elderly, and diabetes).…”

“…EPC-mobilizing effect of ticagrelor might be mediated by enhancement of plasma adenosine concentration beyond its antiplatelet effect [15,17]. Although the guidelines recommended ticagrelor or prasugrel in ACS patients, clinical data from East Asians have shown significantly increased risk of serious bleeding without definite benefit in ischemic risk among ACS patients [18,19].…”