Evaluation of pharmacokinetic, pharmacodynamic, efficacy, and safety data of low-dose ticagrelor versus standard dose in East Asians: a systematic review

Abstract

East Asians are prone to higher systemic exposure and increased risk of bleeding compared to other races after administration of antiplatelet agent(s). The aim of this systematic review was to compare and evaluate the appropriateness of a lower dose versus standard dose of ticagrelor in East Asians. A systematic search was conducted in PubMed, EMBASE, and Cochrane databases for studies comparing low versus standard doses of ticagrelor in East Asian populations; a total of seven studies were included in the review. Pharmacokinetic (PK), pharmacodynamic (PD), clinical efficacy, and safety data were collected. PK data demonstrated that the Cmax and area under the curve (AUC) of ticagrelor increased dose-proportionally. PD data indicated that while the low dose of ticagrelor resulted in less antiplatelet activity in three of the five PD studies, in the other studies, there were no differences between low and standard doses. There were two clinical studies included in this review, which showed that the efficacy was similar between the low and standard doses, but both studies were limited by the number of patients included. While there were generally greater incidence of adverse events observed in the standard ticagrelor dose, the magnitude or actual difference between the two doses is difficult to determine due to lack of consistent data. In East Asians, the appropriateness of the low-dose ticagrelor cannot be determined based on the currently available evidence. Additional large-scale and longer duration studies are warranted.

Validated liquid chromatography–tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma

“…Low‐dose ticagrelor (≤90 mg) showed lower adverse effect originating rate and similar antiplatelet efficacy to standard‐dose of ticagrelor (180 mg). Some researchers proposed low‐dose ticagrelor (90, 60 or 45 mg) for clinical treatment (Lee et al, ; Li et al, ; Storey et al, ).…”

“…Moreover, some methods did not seem sensitive enough for pharmacokinetic studies for low doses of ticagrelor (≤90 mg) (Peng et al, ; Sillén et al, ; Sillén et al, ). Low‐dose ticagrelor has been recommended in clinical therapy because it yields similar antiplatelet efficacy and has fewer side reactions compared with standard‐dose ticagrelor (180 mg) (Lee, Kim, Choi, Lee, & Lee, ; Li et al, ; Storey et al, ). Therefore, in the present study, we developed and validated a rapid, sensitive and convenient LC–MS/MS method to determine ticagrelor and AR‐C124910XX in human plasma by protein precipitation in a run‐time of 3.4 min with an LLOQ of 0.781 ng/mL.…”

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study

“…Several studies explored low-dose ticagrelor regimens in East Asian ethnicity [ 9 ]. East Asians are susceptible to increased bleeding events when compared to other races after the administration of antiplatelet agents [ 22 – 24 ].…”

“…East Asians are susceptible to increased bleeding events when compared to other races after the administration of antiplatelet agents [ 22 – 24 ]. A recent systematic review, including two clinical studies, compared and evaluated the niche of a lower dose versus standard dose of ticagrelor in East Asians, which revealed similar efficacy [ 9 ]. Generally, there was a higher incidence of adverse events observed in the standard ticagrelor dose; however, no formal conclusions could be drawn, as the studies were hindered by limited patient enrollment and outcomes, warranting larger-scale studies [ 9 ].…”

“…In the South Asian, Trinidadian, and Caribbean populations, the literature is not replete with evidence comparing low versus standard doses of ticagrelor to evaluate clinical effectiveness and safety. A recent East Asian systematic review suggested that low-dose ticagrelor revealed an antiplatelet efficacy similar to that of standard-dose ticagrelor, which was faster and more potent than clopidogrel, however, required further evaluation in a large-scale randomized clinical trial [ 9 ]. These findings raised the question as to whether the current recommended dose of ticagrelor is suitable for the Trinidadian population, a population often described as multiethnic and cosmopolitan, comprising an admixture of South Asian, Caribbean Black, East Asian, Arabic, and Caucasian ancestries [ 6 , 10 ].…”