Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843

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How Can We Prevent Both Bleeding and Ischemic Events After Percutaneous Coronary Intervention in High-Bleeding Risk Patients?
Hideki Kitahara
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ジャーナル オープンアクセス HTML 早期公開

論文ID: CJ-22-0277

この記事には本公開記事があります。
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Recent guidelines of antithrombotic therapy in patients with coronary artery disease (CAD) recommend a shorter duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). The Japanese Circulation Society’s guideline 2020 focused update recommends 1- to 3-month DAPT after PCI, unless patients are at low bleeding risk and high thrombotic risk. Data from previous large-scale randomized controlled trials have supported short-term DAPT followed by P2Y12 inhibitor monotherapy because of the decrease in bleeding events and comparable incidence of ischemic events when compared with long-term DAPT. Because most of such pivotal trials have been conducted in foreign countries (except for STOPDAPT-2 trial),1 it seems prudent to consider racial differences and country of origin when selecting an antithrombotic treatment strategy. Previously, it has been reported that East Asians have higher bleeding risk and lower ischemic risk compared with other races (i.e., the East Asian paradox).2 In addition, the occurrence of stent thrombosis is less frequent in East Asian patients compared with Western patients, especially in the era of 1st-generation drug-eluting stents.3 In terms of the PCI procedure, frequent use of intracoronary imaging is a feature in Japan, which might be associated with the lower incidence of stent thrombosis and ischemic events.4 Furthermore, the approved doses of some antiplatelet agents are lower in Japan than in Western countries (e.g., ticlopidine and prasugrel). Based on the unique indication approved in Japan, ticagrelor is usually considered if both clopidogrel and prasugrel are contraindicated because of frequent bleeding events reported in East Asian patients.5 Thus, it may be necessary to establish a dedicated antithrombotic treatment strategy after PCI considering the distinctive environments of each country and its native population.

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As East Asians tend to be at low thrombotic risk and high bleeding risk (HBR), special emphasis should probably be placed on HBR in this population. Although several international trials have included Japanese patients as part of their study enrollment,6 there are limited data regarding short-term DAPT in Japanese HBR patients. The PENDULUM mono study is a large-scale registry conducted in Japan, demonstrating the feasibility of single-antiplatelet therapy (SAPT) with prasugrel after short-term DAPT in HBR patients.7 Previous comparison of 12-month outcomes in matched patients of the PENDULUM mono and PENDULUM registry showed that the incidence of bleeding events tended to be lower with prasugrel SAPT after short-term DAPT compared with long-term DAPT without any increase in adverse events.8 However, the effect of prasugrel SAPT after short-term DAPT on long-term clinical outcomes beyond 1 year after PCI has not been investigated.

In this issue of the Journal, Nakagawa et al9 report their comparison of 2-year clinical outcomes between patients with prasugrel SAPT after short-term DAPT (cohort from PENDULUM mono) and long-term DAPT (cohort from PENDULUM registry) after PCI in a Japanese HBR population. To compare data from 2 different studies, the patients enrolled in the PENDULUM registry who fulfilled the HBR criteria of the PENDULUM mono study were selected as the historical control. The results showed that HBR patients with prasugrel SAPT after short-term DAPT tended to have both lower bleeding and ischemic events compared with long-term DAPT patients, and this tendency was especially obvious for ischemic events beyond 1 year after PCI.

It is still unclear which antiplatelet agent is best for SAPT after short-term DAPT after PCI. Most of the previous studies evaluating short-term DAPT have investigated P2Y12 inhibitor monotherapy.1 In the HOST-EXAM trial, clopidogrel monotherapy was superior to aspirin monotherapy in preventing adverse clinical events as chronic maintenance therapy after PCI.10 Therefore, P2Y12 inhibitor monotherapy may be better than aspirin monotherapy after short-term DAPT. Regarding the selection of P2Y12 inhibitor after short-term DAPT, most of the previous studies have supported the use of clopidogrel and ticagrelor monotherapy, but prasugrel monotherapy has not been sufficiently evaluated. Because the antiplatelet effect of clopidogrel is weakened in patients with the poor metabolizer phenotype of CYP2C19, clopidogrel is less effective in preventing cardiovascular events after PCI in such patients.11 It is well known that the prevalence of CYP2C19 poor metabolizers is much higher among East Asian patients than other races.12 In the recent STOPDAPT-2 ACS trial, 1-month DAPT followed by clopidogrel SAPT did not demonstrate non-inferiority to 12-month DAPT for the net clinical outcomes including ischemic and bleeding events.13 Clopidogrel monotherapy after only 1-month DAPT might be insufficient for most acute coronary syndrome patients. On the other hand, the effect of prasugrel is less influenced by CYP2C19 polymorphisms, and even low-dose prasugrel (maintenance dose: 3.75 mg/day) reportedly achieves stronger platelet inhibition than clopidogrel in CAD patients.14 Practically, better clinical outcomes without a significant increase in bleeding events after PCI compared with clopidogrel have been reported.15 Therefore, low-dose prasugrel SAPT after short-term DAPT can be a balanced antithrombotic therapy for preventing both bleeding and ischemic events in HBR patients undergoing PCI (Figure).

Figure.

Hypothetical optimal antithrombotic strategy after PCI in East Asian patients. DAPT, dual-antiplatelet therapy; GI, gastrointestinal; H. pylori, Helicobacter pylori; HBR, high bleeding risk; PCI, percutaneous coronary intervention; SAPT, single-antiplatelet therapy.

Regarding future directions in this field, further studies are required to investigate the effect of low-dose prasugrel SAPT on very long-term outcomes after PCI, because lifelong treatment with antiplatelet therapy is required in CAD patients. In addition, some clinical studies are currently being conducted to evaluate prasugrel SAPT just after PCI (ASET JAPAN pilot study, ClinicalTrials.gov: NCT05117866) or complete aspirin-free prasugrel SAPT after PCI (STOPDAPT-3 study, ClinicalTrials.gov: NCT04609111) in Japan, which might provide innovative results for the antithrombotic strategy after PCI.

Disclosures

The author reports no conflict of interest.

References
 
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