Coronary Intervention
Impact of Platelet Reactivity on Ischemic and Bleeding Events After Percutaneous Coronary Intervention ― A Long-Term Perspective ―
2022 Volume 86 Issue 9 Pages 1350-1351
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2022 Volume 86 Issue 9 Pages 1350-1351
In recent years, assessment of the bleeding risk in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents has become a priority, especially after the publication regarding the standard definition of patients at a high bleeding risk (HBR) from the Academic Research Consortium in 2019.1 Current guidelines have shifted toward recommending short-term dual-antiplatelet therapy (DAPT), particularly in patients with HBR undergoing PCI.2 However, assessing and achieving the correct balance of ischemic and bleeding risks in individual cases is difficult, and physicians are continually facing this dilemma. With regard to risk stratification, platelet function testing is considered a potential tool to achieve personalized antiplatelet therapy and help balance ischemic and bleeding risks.3 Numerous studies have reported the effect of platelet reactivity measured by platelet function testing on short-term post-PCI outcomes, and most suggest that high platelet reactivity is associated with a higher incidence of ischemic events.4 However, limited data are available regarding the association between platelet reactivity and long-term (especially >2 years) clinical outcomes after PCI.5,6 Additionally, few studies have addressed this important issue in East Asians,6 who tend to have a lower incidence of ischemic events and a higher incidence of bleeding events, despite their high platelet reactivity, than Western populations, commonly known as the “East Asian paradox”.7
Article p 1339
In this issue of the Journal, Kadota et al8 report on the effect of platelet reactivity on 30-month clinical outcomes after PCI, including ischemic and bleeding events, using data from the Japanese multicenter PENDULUM registry. Their study showed that major adverse cardiac or cerebrovascular events (MACCE) consistently occurred even after 12 months, whereas the increase in major bleeding events slowed after 12 months, partly because of the cessation of DAPT. Ischemic and bleeding events were more frequently observed in patients with a high platelet reactivity (P2Y12 reaction units [PRU] >208) than in those without at 30 months. However, the PRU value measured immediately after the index PCI was not an independent predictor of these adverse outcomes after the adjustment of confounding variables. Notably, this study represents Japanese real-world clinical practice, including a high frequency of imaging-guided PCI (94%) and transradial approach (72%), and a high prescription rate of proton pump inhibitors (84.6%) and antihyperlipidemic agents (86.3%). The 12-month results of the PENDULUM registry previously showed that high platelet reactivity was independently associated with ischemic, but not major bleeding events, especially in patients with HBR.9 However, in the study by Kadota et al8 from the same registry, high platelet reactivity was not an independent predictor of 30-month ischemic and bleeding events, which suggested different effects on short- and long-term outcomes. Their study indicated that a long-term perspective is important when following patients undergoing PCI. Clinical studies regarding the effect of platelet reactivity on long-term outcomes in patients undergoing PCI are summarized in the Table.5,6,8 Although the study results are partly inconsistent, differences in patients’ characteristics, study periods, healthcare settings, antiplatelet regimens, and the duration of DAPT in each country are potential explanations for these findings.
| Kadota et al8 | Stuckey et al5 | Lee et al6 | |
|---|---|---|---|
| Year of publication/country | 2022/Japan | 2017/USA and Germany | 2019/South Korea |
| Study design | Prospective, multicenter registry |
Prospective, multicenter registry |
Retrospective, single-center study |
| Sample size/mean age (years) |
n=6,422/70.0 | n=8,582/64 | n=814/63.4 |
| Antiplatelet regimen | Aspirin, clopidogrel, prasugrel | Aspirin, clopidogrel | Aspirin, clopidogrel, cilostazol |
| DAPT continuation rate | 59.3% at 12 months, and 26.4% at 30 months |
80.8% at 12 months, and 53.9% at 24 months |
Data not shown (essentially, DAPT continued for at least 12 months after PCI) |
| Primary outcomes and follow-up period |
MACCE and major bleeding at 30 months |
Definite or probable stent thrombosis at 2 years |
All-cause death at 48 months |
| Major findings | Patients with high platelet reactivity had MACCE and major bleeding more frequently than those without at 30 months, but high platelet reactivity itself was not an independent predictor of these adverse outcomes after multivariate adjustment |
Even after multivariate adjustment, high platelet reactivity was significantly associated with a 2-year incidence of definite or probable stent thrombosis and myocardial infarction, and inversely associated with clinically relevant bleeding events |
All-cause mortality rate at 48 months was significantly higher in the low platelet reactivity (PRU <85) and high platelet reactivity (PRU ≥208) groups than in the normal platelet reactivity group (85≤PRU<208) |
DAPT, dual-antiplatelet therapy; MACCE, major adverse cardiac or cerebrovascular events; PCI, percutaneous coronary intervention; PRU, P2Y12 reaction units.
Importantly, the study by Kadota et al8 included a large number of older patients with HBR factors, mainly because of the considerably aging society in Japan. Given the contents of the updated guideline from the Japanese Circulation Society,2 the duration of DAPT remained relatively long in the PENDULUM registry,8 but was shorter than that in the ADAPT-DES study.5 Additionally, platelet reactivity might be affected not only by antiplatelet agents, but also the patient’s background. Previous studies showed that the presence of anemia or chronic kidney disease (CKD) was associated with high platelet reactivity.10,11 These conditions are common comorbidities in Japanese patients undergoing PCI.12 Notably, although the presence of these conditions was an independent predictor of MACCE, high platelet reactivity itself was not,10,11 which indicated a causal relationship between such multiple comorbidities and adverse outcomes.2,12 These findings are consistent with the study results of Kadota et al,8 who found that anemia and CKD were independent predictors of MACCE and major bleeding at 30 months, whereas a high PRU value was not. Therefore, high platelet reactivity may be a surrogate marker for patients with multiple comorbidities. Indeed, patients with high PRU values had a higher prevalence of anemia, CKD, diabetes mellitus, heart failure, and peripheral artery disease than those without in the PENDULUM registry.8 The importance of personalized antiplatelet therapy for these patients with multiple comorbidities has rapidly increased in the recent aging society.
Although the efficacy of platelet function testing remains uncertain, even in recent randomized controlled trials,13 the study by Kadota et al8 suggests the need for further clinical research regarding the effect of platelet reactivity on long-term outcomes after PCI, especially in the recent, short DAPT era. There is still room for discussion, and hopefully, more detailed and more extensive-scale studies will yield additional knowledge.
The author declares that there are no conflicts of interest.
