This real-world study included 3,077 ACS patients who received prasugrel therapy after PCI. Among the entire population, 726 patients were P2Y12 inhibitor-naïve, and the other 2,351 were prescribed prasugrel as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The incidence of MACCE, defined as cardiovascular death, non-fatal MI, non-fatal stroke, or TIMI major bleeding unrelated to CABG, was 1.8% in the entire study population, with no significant difference found between the naïve and the switch cohort. Also, no significant differences were found between the cohorts in terms of the key secondary endpoints and adverse events (Fig. 5).
The study provided clinically relevant insight into the safety and effectiveness of prasugrel in Korean ACS patients who are potential candidates for treatment with this potent P2Y12 inhibitor. In the pivotal trial of prasugrel (TRITON-TIMI 38), the primary efficacy endpoint (a composite of cardiovascular mortality, non-fatal MI, or non-fatal stroke) occurred in 9.9% and major bleeding in 2.4% of patients who received this agent(5). Meanwhile, in a recent Korean PMS study which included 3,283 patients with ACS who underwent successful PCI, the efficacy outcome (a composite of cardiovascular death, MI, stroke, stent thrombosis or unplanned coronary revascularization) occurred in 0.85% and major bleeding events in 0.93%(14). The event rate in our study was markedly lower than that of the pivotal trial(5), but similar as in the recent PMS study of Korean patients(14). According to the authors of the latter study, the lower incidence of the composite endpoint defined as cardiovascular death, MI, stroke, stent thrombosis and unplanned CABG might be attributed to selective characteristics of the patients, with a lesser representation of those with established risk factors of bleeding, as well as to the progress in the strut design and drug coating of stents(15).
According to the literature, the decision to switch from one antiplatelet agent to another may be driven by various factors, including clinical setting, patient characteristics, concomitant therapies, costs, social issues, development of side effects, medication adherence, and patient/physician preference(17). However, it needs to be stressed that although switching between P2Y12 receptor-inhibiting therapies has been practiced increasingly nowadays, it has not been systematized in any published guidelines, and most evidence and recommendations in this matter originate from pharmacodynamic and registry data(6, 17, 18, 19). Our present study identified a number of reasons to switch to prasugrel. The most common cause was the necessity for a more potent antiplatelet agent (56.3%), resulting in a change from clopidogrel to prasugrel. The second most common reason (27.7%) was an intent to increase the medication compliance through switching from a twice-daily regimen (ticagrelor) to a once-daily regimen (prasugrel). The third cause was the occurrence of adverse events after the previously administered drug (10.5%). Such a distribution of the reasons to switch reflects the strengths of prasugrel as a potent P2Y12 inhibitor with a low adverse event rate and the once-daily regimen that promotes higher medication compliance. Regarding the clinical outcomes, they appeared to be similar in the naïve and switch cohort, even though the latter included patients with more clinical and procedural risk factors. Overall, prasugrel was well-tolerated and equally efficacious in all patients, even if not used as a primary treatment.
The results of the present study should be discussed in the context of the East Asian paradox. Based on the observation that East Asian patients are less prone to thrombotic events and more prone to bleeding, it has been suggested that their threshold of platelet reactivity is different than in Caucasians(20). While this notion was confirmed in the case of clopidogrel(11), the results for the potent P2Y12 inhibitors in the East Asian population are inconclusive, with anti-ischemic benefits outweighing the risk of bleeding in some(14, 21, 22, 23) albeit not all studies(9, 24). As a result, many physicians in South Korea are still reluctant to apply the Western guidelines for antiplatelet agent use(10). However, the results of the present study, as well as the outcomes of the recent PMS study(14), suggest that prasugrel can be used safely in Korean ACS patients after PCI.
The primary limitation of this study stems from the lack of a control group. Furthermore, no robust statistical analyses could be conducted given the small size of some subgroups. While these limitations should be considered during the interpretation of the results, also the strengths of the study related to its real-world character should be highlighted, namely, large sample size and access to information on atypical prescription patterns.