Coronary Intervention
Stratifying Bleeding Risk and Beyond ― Predicting Where Bleeding Will Occur ―
2022 Volume 86 Issue 5 Pages 784-786
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2022 Volume 86 Issue 5 Pages 784-786
The optimal duration of dual antiplatelet therapy (DAPT) required after percutaneous coronary intervention (PCI) is not uniform in all patients, because the balance between the risks of bleeding and thrombosis varies from patient to patient. The advent of second-generation drug-eluting stents (G2-DES) has contributed significantly to reducing the incidence of stent thrombosis (ST) after PCI, and has already achieved equal or better control of ST than bare-metal stents.1 Conversely, the longer the DAPT period, the higher the incidence of bleeding events and the associated mortality.2 In addition, patients with coronary artery disease (CAD) often have atrial fibrillation (AF), which requires oral anticoagulants (OAC) for stroke prevention. The WOEST (What is the Optimal antiplatElet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing) trial demonstrated that clopidogrel alone after PCI significantly reduced bleeding events without increasing thrombotic events at 1 year compared with clopidogrel plus aspirin in PCI patients who take OAC.3 Furthermore, in patients with chronic stable CAD comorbid with AF, rivaroxaban alone significantly reduced bleeding/thrombotic events and all-cause mortality compared with the combination of antiplatelet agent plus OAC.4 Based on all these observations, the focus of post-PCI antithrombotic therapy has currently shifted from simply reducing thrombotic risk to safely minimizing bleeding risk.
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The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria5 effectively stratify bleeding risk in patients undergoing PCI, resulting in the criteria becoming clinically essential for decisions regarding antithrombotic strategy. However, whether the ARC-HBR criteria apply to the prediction model of long-term bleeding outcomes after PCI with G2-DES has been unknown.
In this issue of the Journal, Taguchi et al report the results of a 7-year follow-up after G2-DES implantation investigating the relationship between ARC-HBR criteria and bleeding outcomes, including gastrointestinal bleeding (GIB) and intracranial bleeding (ICB).6 Taguchi et al identified 309 patients with bleeding events in 3,453 patients during the follow-up period, nearly 80% of which were major bleeding events consisting of GIB (39.5%) and ICB (39.2%).6 The ARC-HBR criteria were associated with the incidence of GIB and ICB, but the predictors of GIB and ICB were different, except for taking OAC. All-cause mortality and major adverse cardiovascular events (MACE) at 7 years were significantly higher in patients with than without GIB and ICB.6
The results of this study are noteworthy for the following reasons. First, the authors demonstrated that the ARC-HBR criteria predict long-term bleeding outcomes in Japanese patients undergoing PCI with G2-DES. The essential significance of this validation seems to be that it answers the questions as to whether the ARC-HBR criteria can be applied to Japanese patients, who have a higher risk of bleeding and a lower risk of thrombosis than non-East Asians,7 and whether the ARC-HBR criteria can predict bleeding outcomes not only in the short term, but also at long-term follow-up after PCI. Second, Taguchi et al found that the predictors of GIB and ICB are different, except for taking OAC.6 In other words, this finding suggests that a long-term prediction model for site-specific bleeding outcomes can be created in patients who have undergone PCI. However, ICB during the long-term follow-up by Taguchi et al constituted a much higher proportion of all bleeding events than ICB evaluated as short-term bleeding outcomes.8 This proportional difference may result in different short- and long-term bleeding predictors. Third, it should be noted that 45.1% of patients in the left main coronary artery (LMCA) stent group discontinued DAPT during follow-up, a significantly lower discontinuation rate than in the non-LMCA stent group (66.4%).6 Costa et al found that long-term DAPT reduced ischemic events only in non-HBR patients undergoing complex PCI and did not reduce ischemic events in HBR patients, regardless of PCI complexity, and increased bleeding risk.9 Conversely, a recent publication in this Journal showed that extended DAPT after LMCA stenting improves thrombosis-related long-term outcomes without increasing major bleeding.10 Therefore, the effect of prolonged DAPT after LMCA stenting on long-term outcomes remains controversial; PCI in LMCA may have various treatment strategies in target lesion and procedural complexity, and further investigations to account for these different results may be warranted. Fourth, interestingly, Taguchi et al identified low body weight (LBW) as an independent predictor for ICB.6 LBW is a crucial feature of frailty, which has become a common comorbidity with the advent of a super-aged society. Increased ICB in patients with LBW may reflect the frailty-related falls and subsequent traumatic ICB. However, these associations are still speculative, and further evidence is required. If interventions for LBW and frailty can reduce bleeding events, we may understand the causative relationship between them. Furthermore, investigating why LBW was not a predictor of GIB may provide new insights into background differences underlying GIB and ICB risk.
Bleeding and thrombotic risks share common clinical features and often coexist in the same patient; Natsuaki et al found that approximately 59% of patients at high thrombotic risk had HBR.11 In addition to stratifying bleeding risk, if we can predict where bleeding will occur, we may be able to reduce bleeding risk by site in a way that moves away from the trade-off as to whether to continue antithrombotics. For example, risk-reducing drugs such as antigastric ulcer agents for GIB and antihypertensive agents for ICB could be considered. This strategy may also include interventions for frailty through cardiac rehabilitation. For cardiologists struggling with the trade-off between the risks of bleeding and thrombosis, more options to reduce bleeding risk should be of great help. Further accumulating evidence is required to establish a scheme to reduce bleeding events, as shown in the Figure. Predicting bleeding site beyond stratifying bleeding risk may provide a more comprehensive and effective way to reduce bleeding events. Further development of this research is expected.
Prevention scheme for bleeding events after second-generation drug-eluting stent (G2-DES) implantation. ARC-HBR, Academic Research Consortium for High Bleeding Risk; CKD, chronic kidney disease; LBW, low body weight; LMCA, left main coronary artery; OAC, oral anticoagulant.
K.K. has received remuneration for lectures from Bayer Yakuhin, Daiichi-Sankyo, Novartis Pharma, and Otsuka Pharmaceutical; has received trust research/joint research funds from Bayer Yakuhin and Daiichi-Sankyo; and has received scholarship funds from Abbott Medical. The remaining authors have no conflicts of interest to declare.
