One-month DAPT after biodegradable-polymer everolimus-eluting stent implantation in women at high-bleeding risk: Insights from the POEM trial.

AIMS: We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR). BACKGROUND: Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated. METHODS: Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study. RESULTS: We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints. CONCLUSIONS: This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR.

A comparative study of the clinical benefits of rivaroxaban and dabigatran in patients with nonvalvular atrial fibrillation with high bleeding risk.

Objective: Rivaroxaban and dabigatran are approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). However, the clinical benefits of rivaroxaban and dabigatran in people with high bleeding risk are unclear. Methods: A retrospective study was conducted on NVAF patients admitted to the First Affiliated Hospital of Zhengzhou University from May 31, 2016 to May 31, 2019. These patients had a high risk of bleeding and were taking at least one study medication. The aim of the study was to evaluate clinical benefits by comparing the efficacy and safety risks of these two medications. Results: A total of 1,301 patients with high bleeding risk were enrolled, including 787 patients in the rivaroxaban group and 514 patients in the dabigatran group. Results of the primary efficacy benefit endpoint were obtained from 104 patients (13.21%) in the rivaroxaban group and 81 (15.76%) patients in the dabigatran group [hazard ratio (HR): 0.860; 95% confidence interval (CI): 0.637-1.162; P = 0.327], this indicates that there was no significant difference between dabigatran and rivaroxaban in preventing stroke and systemic embolism in patients with high bleeding risk NVAF. The principal safety end points were observed in 49 (6.23%) patients in the rivaroxaban group and in 36 (7.00%) patients in the dabigatran group (HR: 0.801 in the rivaroxaban group; 95% CI: 0.512-1.255; P = 0.333), this indicates that there was no a significant difference in reducing fatal bleeding and critical organ bleeding. With respect to secondary efficacy and benefit endpoints, 28 (3.56%) patients in the rivaroxaban group and 26 (5.06%) patients in the dabigatran group died, with an HR of 0.725 (95% CI: 0.425-1.238; P = 0.239); 32 (4.07%) patients in the rivaroxaban group; and 31 (6.03%) patients in the dabigatran group had myocardial infarction (MI), with an HR of 0.668 (95% CI: 0.405-1.102, P = 0.114) in the rivaroxaban group, this indicates that there was no significant difference between dabigatran and rivaroxaban in preventing all-cause death and MI. Conclusions: In NVAF patients with high bleeding risk, there was no significant difference between dabigatran and rivaroxaban in preventing stroke and systemic embolism. There was also no significant difference between dabigatran and rivaroxaban in reducing fatal and critical organ bleeding. Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2100052454.

Dual antiplatelet therapy duration and stent type in patients with high bleeding risk: A systematic review and network meta-analysis.

BACKGROUND: It is uncertain whether the efficacy and safety of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) vary according to DAPT duration and stent type (e.g., durable polymer drug-eluting stents (DP-DESs), biodegradable polymer DESs (BP-DESs), or polymer-free drug-coated stents (PF-DCSs)). We aimed to study the stent type and DAPT duration appropriate for patients with HBR. METHODS: PubMed and EMBASE were searched until October 2023. Randomized controlled trials (RCTs) involving patients with HBR that compared standard DAPT (6-12 months) with DP- or BP-DES versus short DAPT (≤3 months) with DP- or BP-DES or PF-DCS or bare-metal stent (BMS) were identified. The primary efficacy outcome was major adverse cardiovascular events (MACEs), defined as cardiovascular death, myocardial infarction (MI), and stroke. The primary safety outcome was major bleeding. Secondary outcomes included MI and stent thrombosis (ST). We performed a network meta-analysis using a random effects model. RESULTS: Thirteen RCTs with a total of 19,418 patients with HBR were included. Compared to standard DAPT with DP-DES, short DAPT with BMS was associated with a higher risk of MACE and MI. For major bleeding, short DAPT strategies were associated with a lower risk than standard DAPT strategies (e.g. short DAPT with DP-DES versus standard DAPT with DP-DES; HR[95% CI]: 0.48[0.28-0.82]). Interestingly, the use of BP-DES was associated with a higher risk of ST than DP-DES (e.g. standard DAPT with BP-DES versus short DAPT with DP-DES; HR[95% CI]: 2.65[1.03-6.79]). CONCLUSIONS: In patients with HBR who underwent percutaneous coronary intervention, a short DAPT strategy with DP-DES should be used since it offers the best combination of efficacy and safety.

Impact of the completeness of revascularization and high bleeding risk status in acute coronary syndrome patients with multi-vessel disease: A retrospective analysis.

Objectives: To investigate the long-term mortality of acute coronary syndrome (ACS) patients with multivessel disease according to the level of completeness of revascularization (CR) and high-bleeding risk (HBR) status. Design Setting and Participants: This retrospective study collected the data of ACS patients with multivessel disease who underwent percutaneous coronary intervention between May 2018 and February 2019. Complete to reasonable revascularization (CR) was defined by the residual Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score (RSS) of 0 to ≤8. The HBR was defined by the PRECISE-DAPT score ≥25. Main Outcome Measures: The all-cause death at 36 months according to the CR and HBR status. Results: A total of 209 patients with 743 lesions were included in the analysis. The median follow-up was 3.6 years. Patients with CR had lower event rates than ICR (4.5 vs. 11.5 per 100 patient-year, HR 0.39, 95% CI 0.22-0.70), p = 0.002). Similar observations were noted when compared between non-HBR and HBR (3.9 vs. 11.1 per 100 patient-year, HR 0.35, 95% CI 0.18-0.64, p < 0.001). Kaplan-Meier analysis revealed that all-cause death was highest among those in the ICR/HBR (40.5%) followed by ICR/non-HBR (28.6%), CR/non-HBR (28.3%) and the lowest among the CR/HBR group (7.1%), log-rank p = <0.001. No significant interaction was observed between the two factors regarding all-cause death (p = 0.10 for interaction). Conclusions: In ACS patients with MVD, the achievement of CR was associated with reducing mortality rates and consistency irrespective of the HBR status. (Trial Registration: TCTR20211222003).

ICARUS score for predicting peri-procedural bleeding in patients undergoing percutaneous coronary intervention with cangrelor.

BACKGROUND: Tools for precise prediction of bleeding risk in patients undergoing percutaneous coronary intervention (PCI) with cangrelor are lacking. METHODS: Consecutive patients undergoing PCI and treated with cangrelor in 7 centers were retrospectively enrolled. The primary endpoint was Bleeding Academic Research Consortium (BARC) BARC 2, 3, or 5 bleeding 48 h after PCI. Predictors of BARC 2-5 bleeding were identified in a derivation cohort and combined into a numerical risk score. Discrimination and calibration were assessed in the derivation and validation cohorts. A threshold to define high bleeding risk (HBR) was identified and its diagnostic accuracy was compared with that of currently recommended bleeding risk scores. RESULTS: 1071 patients undergoing PCI with cangrelor were included. Fifty-four patients (5 %) experienced a BARC 2-5 bleeding, of whom 24 (44 %) from the access site. Age ≥ 75 years (odds ratio [OR] 2.58, 95 % confidence interval [CI] 1.21-5.48, p = 0.01), acute coronary syndrome at presentation (OR 8.14, 95 % CI 2.28-52, p = 0.01), and femoral access (OR 6.21, 95 % CI 2.71-14, p < 0.001) independently predicted BARC 2-5 bleeding at 48 h after PCI. The three items were combined to form a new risk score, the ICARUS score, showing good discrimination in both the derivation (area under the curve [AUC] 0.78) and internal validation (AUC 0.77) cohorts, and excellent calibration. An ICARUS score > 9 points accurately identified patients at HBR, showing better discrimination than other risk scores. CONCLUSIONS: A risk score based on age, clinical presentation and access site, predicts the risk of periprocedural bleeding in patients receiving cangrelor (ClinicalTrials.gov ID: NCT05505591).

High Bleeding Risk in Patients Undergoing Coronary and Structural Heart Interventions.

Percutaneous coronary and structural heart interventions are increasingly preferred over cardiac surgery due to reduced rates of periprocedural complications and faster recovery but often require postprocedural antithrombotic therapy for the prevention of local thrombotic events. Antithrombotic therapy is inevitably associated with increased bleeding, the extent of which is proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which may outweigh the expected benefit of reducing thrombotic events. Herein, we provide a comprehensive description of the classification and clinical relevance of high bleeding risk in patients undergoing coronary and structural heart interventions.

Feasibility of anticoagulation on demand after percutaneous coronary intervention in high-bleeding risk patients with paroxysmal atrial fibrillation: the INTERMITTENT registry.

Aims: This study evaluated the feasibility of the intermittent use of direct oral anticoagulants (DOACs) guided by continuous rhythm monitoring via a clinically validated wearable smart device in high-bleeding risk (HBR) patients with symptomatic paroxysmal atrial fibrillation (AF) otherwise subjected to chronic anticoagulation after percutaneous coronary intervention (PCI). Methods and results: The INTERMITTENT registry was a 3-year prospective observational study at eight Italian centres. Inclusion criteria were elective or urgent PCI, Academic Research Consortium HBR criteria, history of symptomatic 12-lead ECG detected paroxysmal AF episodes, indication to DOACs, and use of a wearable smart device (Apple Watch™). Thirty days after PCI, patients free of AF episodes discontinued DOAC. However, if an AF episode lasting >6 min or a total AF burden > 6 h over 24 h was detected, DOAC was initiated for 30 consecutive days, and withdrawn afterwards if no further AF episodes occurred. At the discretion of the referring physician, intermittent anticoagulation was offered to 89 patients, whereas continuous treatment with DOACs was prescribed to 151 patients. During a follow-up of 298 ± 87 days, the average duration of oral anticoagulation was significantly shorter in the intermittent anticoagulation group (176 ± 43 days, P = 0.0001), representing a 40% reduction in anticoagulation time compared to the continuous group. Ischaemic and bleeding endpoints were not significantly different between the two groups. Propensity score-matching resulted in a total of 69 matched patients with intermittent vs. continuous anticoagulation, respectively. During a follow-up of 291 ± 63 days, there was a significant 46% reduction in anticoagulation time in the intermittent compared to the continuous group (P = 0.0001). Conclusion: In HBR patients with a history of paroxysmal AF episodes who underwent PCI, intermittent anticoagulation guided by continuous rhythm monitoring with a wearable device was feasible and decreased significantly the duration of anticoagulation.

Optimal management of high bleeding risk patients undergoing percutaneous coronary interventions: Where do we stand?

Percutaneous coronary interventions (PCI) are the mainstay of treating obstructive coronary artery disease. However, procedural planning and individualization of the procedure is necessary for different patient phenotypes to optimize outcomes. Specifically, post-PCI pharmacotherapy with antiplatelets complicates the management of patients at high bleeding risk due to comorbidities, such as atrial fibrillation. Aiming to limit post-procedural adverse events and reduce the procedure-related bleeding risk, several novel technologies and hypotheses have been tested in clinical practice. Such frontiers include limiting the duration of dual antiplatelet therapy or even prescribing single regimens, using drug-coated balloons for performing the intervention and the effect of imaging-guided PCI in optimizing stent expansion. Furthermore, specific instruction in different patient phenotypes, such as atrial fibrillation and chronic kidney disease, are emerging, as despite both pathologies being considered at high bleeding risk, one size does not fit all. Thus, our review will provide all the recent updates on the field as well as algorithms and expert opinions on how to manage this, particularly common, phenotype of patient.

Novel Stentless Strategy With Perfusion and Drug-Coated Balloons for Treating Acute Coronary Syndrome.

Background: The challenge with the stentless strategy is that the method of optimal predilatation, and predictors of success remain unknown. Studies involving the stentless strategy prior to predilatation are limited. This study aimed to evaluate the long-term efficacy and safety of a new stentless strategy for treating acute coronary syndrome (ACS) using gradual, prolonged predilation with a perfusion balloon combined with a drug-coated balloon (DCB). Methods: This was a single-center, prospective, single-arm study. A total of 30 patients with ACS underwent gradual, prolonged predilation using a perfusion balloon for 10 minutes, followed by additional dilation using a DCB. The primary end point was target vessel failure at 24 months. Secondary end points were a composite of acute end points, including stentless strategy success rate, procedural complications, final grade of coronary dissection, acute coronary occlusion, in-hospital major adverse cardiac events, and a chronic end point of target vessel failure at 24 months. Results: A successful stentless strategy was achieved in 24 patients (80%), and 2 (8.3%) patients required ischemic-driven target lesion revascularization in the chronic phase. Six (20%) patients required stent placement due to type C dissection or acute recoil. No acute occlusion and in-hospital major adverse cardiac events were reported. Conclusions: A novel stentless strategy using predilation with a perfusion balloon and DCB may be helpful for the revascularization of patients with ACS.

One-Month Dual Antiplatelet Therapy in High Bleeding Risk Asian Patients Undergoing Percutaneous Coronary Intervention　- Onyx ONE Clear 2-Year Results.

Background: One-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) with the Resolute OnyxTM zotarolimus-eluting stents (ZES) is safe and effective. Asian patients have a unique ischemia/bleeding risk profile. Here, we compare the outcomes between Asian and non-Asian patients after PCI and 1-month DAPT. Methods and Results: Onyx ONE Clear was a prospective, multicenter study enrolling HBR patients undergoing PCI with the Resolute Onyx ZES (ClinicalTrials.gov identifier NCT03647475). Event-free patients after 1-month DAPT transitioned to single antiplatelet therapy. Clinical outcomes between 1 month and 2 years were compared between patients from Asian and non-Asian countries after 1 : 1 propensity score matching accounting for baseline differences. Patients from Asian countries represented 18% (n=273) of the study group (n=1,507). Non-Asian patients had greater clinical complexity; however, these differences were minimal after matching. There were no significant differences in ischemic outcomes between matched cohorts from 1 month to 2 years, including the primary composite endpoint of cardiac death or myocardial infarction (12% vs. 12%; P>0.99). However, there were significantly fewer Bleeding Academic Research Consortium types 3-5 bleeding events in the Asian vs. non-Asian cohort (4% vs. 9%; P=0.007), despite similar bleeding risk profiles after matching. Conclusions: After propensity score matching, HBR patients from Asian countries undergoing PCI treated with 1-month DAPT had similar ischemic outcomes but fewer bleeding events between 1 month and 2 years compared with patients from non-Asian countries.

One-month DAPT after biodegradable-polymer everolimus-eluting stent implantation in patients at high-bleeding risk: an individual patient data pooled analysis of the SENIOR and POEM trials.

Aims: Dual antiplatelet therapy (DAPT) can be shortened up to 1 month in high-bleeding risk (HBR) patients receiving a contemporary biodegradable-polymer sirolimus-eluting stent. We aimed to summarize the evidence on a similar DAPT regimen after biodegradable-polymer everolimus-eluting stent (EES) implantation in patients at HBR. Methods and results: We pooled the individual participant data from the available trials evaluating this strategy, namely, the SENIOR and the POEM trials. Inclusion criteria were ≥1 biodegradable-polymer EES implantation and ≤1-month duration of DAPT. The primary endpoint was the 1-year composite of cardiovascular death, myocardial infarction, or stroke. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3-5 bleeding. Landmark analyses were performed at 1 month, the time point for intended DAPT interruption. We included 766 participants (age 77.5 ± 8.2 years, women 31.9%), 323 from the SENIOR and 443 from the POEM trial. The primary endpoint occurred in 45 participants (6.0%; 95% confidence interval [CI], 4.3-7.7%) through 1 year of follow-up, with 21 (2.8%; 95% CI, 1.6-3.9%) events during the first month and 24 (3.4%; 95% CI, 2.0-4.7%) thereafter. The incidences of cardiovascular death, myocardial infarction, and stroke were 2.2% (95% CI, 0.36-2.50%), 3.1% (95% CI, 1.8-4.3%), and 1.2% (95% CI, 0.4-2.0%), respectively. BARC type 3-5 bleeding ocuurred in 1.1% (95% CI, 0.3-1.8%) at 1 month and 2.9% (95% CI, 1.6-4.1%) at 1 year. Conclusion: HBR patients receiving biodegradable-polymer EES had few ischemic and bleeding events when given 1 month of DAPT. One-month DAPT after biodegradable-polymer EES implantation seems safe in patients at HBR.

Long-term outcomes of high bleeding risk patients undergoing percutaneous coronary intervention: a Korean nationwide registry.

BACKGROUND AND AIMS: Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients. METHODS: This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events. RESULTS: Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P < .001) and ischaemic events (33.8% vs. 14.4%, P < .001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04-3.21, P < .001] and for ischaemic events (HR 2.50, 95% CI 2.45-2.56, P < .001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66-3.79, P < .001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion. CONCLUSIONS: Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients.

Therapeutic strategies aiming at the reduction of the antiplatelet intensity should not overlook the ischemic risk in patients with coronary syndromes.

De-escalation of dual antiplatelet therapy (DAPT) is gaining traction as a strategy to reduce bleeding risks while ensuring ischemic outcomes. Undiscriminating de-escalation, notably in patients with high ischemic risk, might expose them to major adverse cardiac events. Platelet function and genetic tests are emerging tools to guide de-escalation, but both present specific drawbacks. Recent meta-analyses have aimed to consolidate the findings of individual trials to provide clearer insights. Yet, limitations remain for patients with concomitant high bleeding and ischemic risks. These high-risk patients are frequently underrepresented in clinical trials, and, therefore, currently available guidelines lack evidence-based recommendations for this subset. While DAPT de-escalation strategies hold promise, the choice of approach, whether clinically or assay-guided, remains complex and should be individualized.

Abbreviated Versus Standard Dual Antiplatelet Therapy Times After Percutaneous Coronary Intervention in Patients With High Bleeding Risk With Acute Coronary Syndrome: Insights From the SWEDEHEART Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS AND RESULTS: Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P=0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups. CONCLUSIONS: In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

One-Month Versus Three-Month Dual-Antiplatelet Therapy in High Bleeding Risk Patients With Chronic Kidney Disease.

Shortening the duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was shown to be effective and safe in patients at high bleeding risk (HBR). We aimed to investigate the effect of 1 versus 3-month DAPT on outcomes after drug-eluting stent in HBR patients with or without chronic kidney disease (CKD). Data from 3 prospective single-arm studies (XIENCE Short DAPT Program) enrolling HBR patients after successful coronary implantation of cobalt-chromium everolimus-eluting stent (XIENCE, Abbott) were analyzed. Subjects were eligible for DAPT discontinuation at 1 or 3 months if free from ischemic events. The primary end point was all-cause death or any myocardial infarction. The key secondary end point was Bleeding Academic Research Consortium Type 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after PCI. CKD was defined as baseline creatinine clearance <60 ml/min. Of 3,286 patients, 1,432 (43.6%) had CKD. One-month versus 3-month DAPT was associated with a similar 12-month risk of the primary outcome irrespective of CKD status (CKD: 9.5% vs 10.9%, adjusted hazard ratio 0.86, 95% confidence interval 0.60 to 1.22; no-CKD: 6.6% vs 5.6%, adjusted hazard ratio 1.15, 95% confidence interval 0.77 to 1.73; p interaction 0.299). Bleeding Academic Research Consortium 2 to 5 bleeding rates were numerically but not significantly lower with 1-month versus 3-month DAPT in both CKD (9.9% vs 12%) and no-CKD (6.4% vs 9.0%) patients. In conclusion, in HBR patients, 1-month versus 3-month DAPT was associated with a similar risk of ischemic complications and a trend toward fewer bleeding events at 12 months after PCI, irrespective of CKD status.

Clinical impact of Academic Research Consortium for High Bleeding-Risk scores on clinical outcomes in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

High bleeding risk (HBR), as defined by the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria, has been recently reported to be associated with an increased risk of major bleeding events and cardiovascular events. We investigated the association between the ARC-HBR score and clinical outcomes in patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). We assessed 328 consecutive patients with stable CAD who underwent PCI between January 2017 and December 2020. We scored the ARC-HBR criteria by assigning 1 point to each major criterion and 0.5 points to each minor criterion. Patients were stratified into low (ARC-HBR score < 1), intermediate (1 ≤ ARC-HBR score < 2), and high (ARC-HBR score ≥ 2) bleeding-risk groups. The primary outcome measure was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. We compared the discriminative abilities of the ARC-HBR score with the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) and ARC-HBR score with Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic risk score. The mean patient age was 70.1 ± 10.2 years (males, 76.8%). During the median follow-up period of 983 (618-1338) days, 44 patients developed MACE. Kaplan-Meier curves showed that a stepwise significant increase in the cumulative incidence of MACE as the ARC-HBR score increased (log-rank p < 0.001). In the time-dependent receiver-operating characteristic curve analysis for predicting MACE within 2 years, the area under the curve (AUC) of the ARC-HBR score was significantly higher than that of the TRS2°P (AUC: 0.825 vs. 0.725, p value for the difference = 0.023) and similar to that of CREDO-Kyoto thrombotic risk score (AUC: 0.825 vs. 0.813, p value for the difference = 0.627). Conclusions: The ARC-HBR score adequately stratified future risk of MACE in patients with stable CAD who underwent PCI. The ARC-HBR score showed a higher discriminative ability for predicting mid-term MACE than the TRS2°P.

Application of the Academic Research Consortium High Bleeding Risk criteria in patients treated with coronary bioresorbable polymer everolimus-eluting stents: Insights from the POEM trial.

BACKGROUND: Previous studies have investigated a 1 to 6-month short dual antiplatelet therapy (S-DAPT) after percutaneous coronary intervention (PCI) with modern drug eluting-stents to reduce bleeding events. OBJECTIVES: To investigate cardiovascular outcomes in patients at high bleeding risk (HBR) according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria after PCI with the Synergy bioresorbable-polymer everolimus-eluting stents (EES). METHODS: We applied ARC-HBR criteria in the population of the prospective, single-arm, multicenter POEM (Performance of Bioresorbable Polymer-Coated Everolimus-Eluting Synergy Stent in Patients at HBR Undergoing Percutaneous Coronary Revascularization Followed by 1-Month Dual Antiplatelet Therapy) trial. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite or probable stent thrombosis at 12 months. RESULTS: The original POEM cohort included 356 patients (80.4 %) fulfilling ARC-HBR criteria. Oral anticoagulant (OAC) usage and age ≥75 years were the most frequent major and minor ARC-HBR criteria, respectively. The ARC-HBR group was mainly represented by men (71.1 %), with 74.4 ± 9.3 years and a high burden of cardiovascular risk factors. DAPT was prescribed in 79.3 %, and single antiplatelet (SAPT) with OAC in 18.7 %. 12-month follow-up was completed in 96.2 %. The primary endpoint occurred in 5.2 % (95 % CI 3.29-8.10) of patients, whereas bleeding Academic Research Consortium type 3-5 occurred in 2.7 % (95 % CI, 1.39 %-5.05 %). CONCLUSION: Previous results of the POEM trial showed positive outcomes regarding ischemic and bleeding events with an S-DAPT regimen after Synergy EES. These results are also confirmed in sub-group analysis when ARC-HBR criteria are applied.

Consecutive or selectively included high bleeding risk patients in the MASTER DAPT screening log and trial.

AIMS: Screening logs have the potential to appraise the actual prevalence and distribution of predefined patient subsets, avoiding selection biases, which are inevitably and potentially present in randomised trials and real-world registries, respectively. We aimed to assess the prevalence of high bleeding risk (HBR) characteristics in the real world and the external validity of the MASTER DAPT trial. METHODS AND RESULTS: All consecutive patients who underwent percutaneous coronary intervention (PCI) for at least two consecutive weeks across 65 sites participating in the trial were entered into a screening log. Of 2,847 consecutive patients, 1,098 (38.6 %) were HBR and 109 (9.9 %) consented for trial participation. PRECISE-DAPT score ≥ 25 was the most frequent HBR feature, followed by advanced age, use of oral anticoagulation (OAC) and anaemia. Compared with consecutive HBR patients, consenting patients were older (≥ 75 years: 69 % versus 62 %, absolute standardized difference [SD] 0.16), more frequently male (78 % versus 71 %, absolute SD 0.18), had higher use of OAC (38 % versus 20 %, absolute SD 0.39), treatment with steroids or nonsteroidal anti-inflammatory drugs (10 % versus 5 %, SD 0.16), and prior cerebrovascular events (10 % versus 6 %, absolute SD 0.18) but lower PRECISE DAPT score ≥ 25 (54 % versus 66 %, absolute SD 0.24). CONCLUSIONS: The HBR criteria distribution differed between consecutive versus selectively included HBR patients, suggesting the existence of selection biases in the trial population.

Negative selection bias for women inclusion in a clinical trial.

INTRODUCTION: Despite the growing awareness towards the importance of adequate representation of women in clinical trials among patients treated with percutaneous coronary intervention (PCI), available evidence continues to demonstrate a skewed distribution of study populations in favour of men. METHODS AND RESULTS: In this pre-specified analysis from the MASTER DAPT screening log and trial, we aimed to investigate the existence of a negative selection bias for women inclusion in a randomized clinical trial. A total of 2847 consecutive patients who underwent coronary revascularization across 65 participating sites, during a median of 14 days, were entered in the screening log, including 1749 (61.4%) non-high bleeding risk (HBR) and 1098 (38.6%) HBR patients, of whom 109 (9.9%) consented for trial participation. Female patients were less represented in consented versus non-consented HBR patients (22% versus 30%, absolute standardized difference: 0.18) and among non-consented eligible versus consented eligible patients (absolute standardized difference 0.14). The observed sex gap was primarily due investigators' choice not to offer study participation to females because deemed at very high risk of bleeding and/or ischemic complications, and only marginally to a slightly higher propensity of females compared to males to refuse study participation. CONCLUSIONS: Female HBR patients undergoing PCI are less prevalent, but also less likely to participate in the trial than male patients, mainly due to investigators' preference.