High Bleeding Risk Patients Research Articles

Coronary Stenting in High Bleeding Risk Patients With Small Coronary Arteries Followed by One-Month Dual Antiplatelet Therapy: Onyx ONE Clear.

Small reference vessel diameters (RVDs) are a predictor of ischemic events after coronary stenting. Among patients at high bleeding risk (HBR) precluding long-term dual antiplatelet therapy (DAPT), those with small vessel disease (SVD) constitute an especially high-risk subgroup. Here, we evaluated the results of a durable-polymer, coronary zotarolimus-eluting stent (ZES) for the treatment of patients with SVD at HBR with 1-month DAPT. In the prospective, multicenter Onyx ONE (One-Month DAPT) Clear study, 1506 patients at HBR treated with a ZES that discontinued DAPT at 30 days were included. The clinical outcomes of patients undergoing treatment of lesions with an RVD of ≤2.5 mm (SVD group, as determined by the angiographic core laboratory) were compared with patients without SVD. The primary end point was the composite of cardiac death or myocardial infarction between 1 and 12 months. Small vessel diameter treatment was performed in 489 (32.5%) patients. Patients with SVD were more likely to be women, have undergone a previous percutaneous intervention, and have multivessel coronary artery disease than patients without SVD. There were no significant differences in lesion, device, or procedural success between the groups. The Kaplan-Meier rate estimate of the primary end point was 8.5% and 6.8% in patients with SVD and those without SVD, respectively (P = .425). No significant differences were found in any secondary end point. The Kaplan-Meier rate of stent thrombosis was 0.6% and 0.8% in patients with SVD and those without SVD, respectively (P = .50). Among patients at HBR treated with a ZES and 1-month DAPT, those with SVD had favorable 12-month ischemic and bleeding outcomes, which were comparable with those of patients with larger caliber vessels.

High bleeding risk in all-comers with ST-segment elevation myocardial infarction and use of P2Y12-inhibitiors

Abstract Background Bleeding has an important prognostic impact in patients with ST-segment elevation myocardial infarction (STEMI), yet stratification of bleeding risk to guide dual antiplatelet therapy (DAPT) is not routinely performed in clinical practice. Purpose To describe high bleeding risk (HBR) patients according to the PRECISE-DAPT (predicting bleeding complications in patients undergoing stent implantation and subsequent DAPT) score and use of P2Y12-inhibitors. Methods This single-centre observational study included consecutive patients with STEMI who were treated with percutaneous coronary intervention (PCI) from 2009–2016. Individual linkage to Danish nationwide registries was conducted to obtain information on diagnoses, claimed drugs, and vital status. Age, prior bleeding diagnosis, and blood samples before PCI (maximum 30 days before hospitalisation) were used to calculate the PRECISE-DAPT score. A score ≥25 was considered as HBR. Due to 26.7% missing on blood parameters (mainly leucocytes), the maximum and minimum values of the missing parameters and respective imputed PRECISE-DAPT scores were calculated. If both the maximum and minimum score were ≥25 or <25, patients were categorised accordingly, and a maximum score of ≥25 and minimum score of <25 as missing. Differences between continuous (median [interquartile range, IQR]) and categorical variables (frequency [percentage]) were assessed using Wilcoxon rank-sum and χ2-test for patients with vs. without HBR. Cumulative incidence of major bleeding (composite of bleedings leading to hospitalisation) and major adverse cardiovascular events (MACE) (composite of all-cause mortality, recurrent MI, and ischemic stroke) 1 year after PCI were plotted for patients with and without HBR. Number of HBR patients alive and collecting a P2Y12-inhibitor prescription within 30 days from discharge was reported. Results We identified 6179 PCI-treated patients with STEMI, of whom 5530 (89.5%) had imputed PRECISE-DAPT scores (Figure 1). A total of 1821 (32.9%) were at HBR, and these were more often female (38.3 vs. 18.2%, p-value<0.001), elderly (median age 75 [IQR 67, 81] vs. 57 years [IQR 51, 64], p-value<0.001), and had more comorbidities (diabetes [16.7 vs. 12.1%], heart failure [16.2 vs. 7.6%], cardiac arrhythmia [24.9 vs. 12.3%], cancer [17.5 vs. 5.7%], and ischemic stroke [8.1 vs. 2.6%], all p-values<0.001) compared with patients not at HBR. One-year cumulative incidence of major bleeding and MACE for patients with and without HBR were plotted (Figure 2). Of the 1431 (78.6%) HBR patients who were alive and claimed a P2Y12-inhibitior prescription 30 days from discharge, 459 (32.1%) were treated with clopidogrel, 672 (46.9%) with ticagrelor, and 300 (21.0%) with prasugrel (Figure 1). Conclusion Every third PCI-treated all-comer with STEMI was at HBR according to the PRECISE-DAPT score. HBR patients were more often treated with potent P2Y12-inhibitors (prasugrel or ticagrelor) instead of clopidogrel. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Short dual antiplatelet therapy duration in high bleeding risk patients undergoing PCI for non-ST-elevation acute coronary syndrome

Abstract Background Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain at increased risk of recurrent ischemic events. An abbreviated dual antiplatelet therapy (DAPT) duration as short as 1 month has been suggested for those at high bleeding risk (HBR). Whether the benefits of 1-month DAPT are preserved in HBR patients presenting with non-ST-elevation ACS (NSTE-ACS) is subject of debate. Purpose To assess the impact of NSTE-ACS presentation on the ischemic and bleeding outcomes of HBR patients undergoing PCI with a cobalt-chromium everolimus-eluting stent followed by a 1-month versus 3-month DAPT. Methods The XIENCE Short DAPT Program encompasses three prospective, international, single-arm studies evaluating the safety and efficacy of a 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT duration. The program enrolled HBR patients who had undergone successful XIENCE stent implantation for acute or chronic coronary syndrome (excluding ST-elevation ACS). Event-free subjects discontinued DAPT at 1 or 3 months post-PCI. The primary endpoint was the composite of all-cause death or myocardial infarction (MI), while the key secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding between 1 and 12 months post-PCI. Ischemic and bleeding events associated with 1-month versus 3-month DAPT were assessed according to clinical presentation using propensity-score (PS) adjustment. Results Out of 3,364 HBR patients (n=1,392 on 1-month DAPT and n=1,972 on 3-month DAPT), 1164 (34.6%) underwent PCI for NSTE-ACS. At 12 months, the risk of death or MI was similar between 1- and 3-month DAPT in patients with (adjHR 1.12, 95% CI 0.73–1.70) and without NSTE-ACS (adjHR 0.92, 95% CI 0.65–1.29; p-interaction = 0.33). Landmark analysis between 1 and 3 months post-PCI showed significant treatment effect modification according to clinical presentation (p-interaction = 0.03) with greater benefit of 1-month DAPT in stable patients. BARC 2–5 bleeding was consistently reduced in both NSTE-ACS (adjHR 0.58, 95% CI 0.38–0.90) and stable patients (adjHR 0.86, 95% CI 0.63–1.18; p-interaction = 0.15). Conclusions Among HBR patients undergoing PCI with an everolimus-eluting stent, 1-month compared with 3-month DAPT was associated with similar 1-year risk of ischemic events and reduced bleeding, irrespective of clinical presentation. Between 1 and 3 months post-PCI, however, stable patients seemed to derive greater net benefit from 1-month DAPT compared to those with NSTE-ACS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Dual antiplatelet therapy for 1 versus 3 months in high bleeding risk patients with or without oral anticoagulant therapy after coronary stenting

Abstract Background A short DAPT duration after coronary stenting has been associated with similar ischemic outcomes and fewer bleeding complications in patients at high bleeding risk (HBR). Whether these effects are preserved irrespective of concomitant oral anticoagulant (OAC) therapy remains unclear. Purpose To evaluate the safety and efficacy of 1-month versus 3-month DAPT among HBR patients with or without indication to OAC therapy who undergo cobalt-chromium everolimus-eluting stent implantation. Methods The XIENCE Short DAPT Program comprises three prospective, international, single-arm studies evaluating 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT in HBR patients who had undergone successful everolimus-eluting XIENCE stent implantation. OAC therapy at discharge was a study inclusion criterion. Subjects were eligible to discontinue DAPT at 1 or 3 months if free from ischemic events and adherent to DAPT. The primary endpoint was the composite of all-cause death or any myocardial infarction (MI). The major secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding. In this exploratory analysis, HBR patients on 1-month DAPT were compared with those on 3-month DAPT according to the presence of background OAC therapy. Ischemic and bleeding outcomes were assessed between 1 and 12 months after index PCI using propensity-score (PS) adjustment. Results A total of 3,364 patients, 1,392 on 1-month DAPT and 1,972 on 3-month DAPT, were eligible for the analyses. Patients on OAC therapy (n=1424, 42.3%) were younger, more often male and of white race, and with a lower prevalence of other HBR criteria such as chronic kidney disease and anemia. The incidence of death or MI at 12 months was similar between the two groups (8.0% vs 7.9%) while BARC 2–5 bleeding was higher in OAC patients (12.2% vs 7.2%). After PS adjustment, 1-month DAPT, compared with 3-month DAPT, did not increase the 1-year risk of death or MI in both OAC (adjHR 0.71, 95% CI 0.47–1.08) and non-OAC patients (adjHR 1.24, 95% CI 0.88–1.75; p-interaction = 0.11). The risk of BARC 2–5 bleeding was consistently reduced in both OAC (adjHR 0.71, 95% CI 0.51–1.00) and non-OAC patients (adjHR 0.77, 95% CI 0.53–1.11; p-interaction = 0.69). Conclusions Among HBR patients undergoing everolimus-eluting stent implantation, 1-month DAPT compared with 3-month DAPT was associated with similar ischemic outcomes and reduced bleeding, regardless of concomitant OAC therapy. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Abbreviated dual antiplatelet therapy after PCI in patients at high bleeding risk: a collaborative meta-analysis of randomized trials

Abstract Aims The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. We appraised an abbreviated compared with a more prolonged DAPT regimen in this setting by using the totality of existing evidence. Methods and results A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated (i.e., short [3 months] or very-short [1 month]) with standard (≥6 months) DAPT in HBR patients. Six trials with 8,409 patients were included. Major or clinically relevant non-major bleeding (MCRB) and major adverse cardiovascular events (MACE) were the co-primary safety and efficacy endpoints. MCRB was lower with abbreviated compared to standard DAPT (risk ratio [RR] 0.63, 95% CI 0.41–0.95; I2=74%). No difference in terms of MACE (RR 1.03, 95% CI 0.89–1.20; I2=0%) all-cause death, cardiovascular death, stent thrombosis or myocardial infarction were observed. Network meta-analysis showed short or very-short DAPT to have the highest probability to prevent bleeding in HBR patients. Conclusion Abbreviated DAPT reduced bleeding without apparent increase in ischemic events in HBR patients undergoing PCI. Three-month or one-month DAPT courses appeared similarly effective to optimize the trade-off for ischemia and bleeding in this population. Funding Acknowledgement Type of funding sources: None.

Comparison between ticagrelor and clopidogrel in high bleeding risk patients with acute coronary syndrome

Abstract Background Potent antiplatelet agents such as ticagrelor are associated with a lower risk of ischemic events than clopidogrel in patients with acute coronary syndrome (ACS). However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in individuals who have a high bleeding risk (HBR). This study aimed to assess treatment outcomes following dual antiplatelet therapy (DAPT) using either ticagrelor or clopidogrel in ACS patients with HBR. Methods All HBR patients enrolled in the SWEDEHEART registry who were discharged with DAPT using ticagrelor or clopidogrel following ACS between 2010 and 2017 were included in this study. Bleeding risk was assessed using the 4-item PRECISE-DAPT score, which consists of age, prior bleeding, haemoglobin concentration and creatinine clearance. HBR was defined as a PRECISE-DAPT score ≥25. Inverse-probability of treatment weighting was used to adjust for baseline differences between the treatment groups. The main analysis consisted of a doubly robust estimation of causal effect using Cox proportional hazards models. Data on major bleeding, recurrent myocardial infarction (MI), ischemic stroke and all-cause mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, ischemic stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and major bleeding. Results Of all ACS patients, 36% (n=25,042) had a PRECISE-DAPT score ≥25. Approximately half of the study participants were treated with ticagrelor (n=11,848). Ticagrelor reduced the risk of MI (hazard ratio [HR], 0.82 [95% CI 0.74–0.91]), ischemic stroke (HR, 0.73 [95% CI 0.60–0.88]) and MACE (HR, 0.90 [95% CI 0.84–0.97]), while also increasing the risk of major bleeding compared to clopidogrel (HR, 1.30 [95% CI 1.16–1.47]). We found no significant differences in all-cause mortality (HR 1.02 [95% CI 0.92–1.12]) and NACE (HR 0.98 [95% CI 0.92–1.05]). Conclusions Ticagrelor was associated with a lower risk of recurrent ischemic events, but a higher risk of major bleeding compared to clopidogrel. There were no significant differences in all-cause mortality and NACE between the treatment groups. These results suggest that more potent antiplatelet agents might not be superior to clopidogrel in ACS patients with HBR. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Stockholm county council

Differential prognosis of patients candidates for standard, short or prolonged dual antiplatelet treatment discharged after an acute coronary syndrome

Abstract Background Current evidence supports the efficacy of prolonged dual antiplatelet treatment prolonged (DAPT) patients at high-ischemic risk and low bleeding risk. In contrast, several trials have demonstrated the efficacy and safety of short DAPT (1,3 o6 months) in high-bleeding risk (HBR) patients. Nonetheless, 12 months of DAPT is the most commonly strategy recommended in patients discharged after an ACS. Methods We evaluated patterns of DAPT candidates in all patients discharged in single center between 2009 and 2019 after an acute coronary syndrome (ACS). Patients categorized in 3 groups: 1) short-DAPT candidates if they met 1 major o 2 minor criteria for HBR, by the 2019 ARC-HBR criteria; 2) prolonged-DAPT candidates if were not HBR and had recurrent ACS, complex percutaneous coronary interventions or diabetes; 3) standard 12 months DAPT if were not include in the previous 2 groups. We evaluated all-cause and cardiovascular mortality, mayor bleeding (MB), and major cardiovascular events (MACE) after discharge. Results We assessed 3,155 patients discharged after an ACS, mean age was 68.4 (13.0), 25.9% were women, 32.5% had diabetes, 13.2% received complex percutaneous coronary interventions and 40.5% were categorized as HBR. After categorization, 1,277 (40.48%) were candidates for short DAPT, 1,203 (38.1%) for standard 12m DAPT and 675 (21.39%) for prolonged DAPT. After a median follow-up was 1032 days (interquartile range 555–1950), all-cause mortality was 15.8%, cardiovascular mortality 10.5%, 35.9% had a first MACE and 6.2% had at least one MB. As shown in figure 1, patients candidates for short or prolonged DAPT had significantly higher rates of all-cause and cardiovascular mortality as well as MACE. In contrast, higher rate of MB was only increased in patients candidates for short-DAPT (figure 2). Multivariate analysis demonstrated higher risk of MB (sHR: 1.60 95% CI 1.10–2.60; p=0.030) only in patients candidates for short-DAPT. In contrast, candidates for short-DAPT has higher risk of all-cause mortality (HR: 2.92 95% CI 1.95–4.37; p<0.01) and cardiovascular mortality (HR: 3.01 95% CI 1.78–5.32; p<0.01) and MACE (HR: 2.22, 95% CI 1.82–2.70; p<0.01). Similarly, patients candidates for prolonged DAPT had higher risk of all-cause mortality (HR: 1.72 95% CI 1.10–2.69; p=0.002), cardiovascular mortality (HR: 2.47 95% CI 1.39–4.40; p=0.017) and MACE (HR: 1.58 95% CI 1.28–1.95; p<0.001). Conclusions Almost two thirds of patients discharged after an ACS would be candidates for short or prolonged DAPT and these patients are at higher risk of MACE and mortality. Patients candidates for short-DAPT had higher risk of MB through the follow-up. These results might reinforce the need of individual assessment of most optimal DAPT duration in all patients discharged after an ACS. Funding Acknowledgement Type of funding sources: None.

Bleeding risk prediction in a large cohort of patients with atrial fibrillation and cancer: a nationwide cohort study

Abstract Introduction The association between cancer types and specific bleeding events in atrial fibrillation (AF) patients has been scarcely investigated. Also, the performance of bleeding risk scores in this high-risk subgroup of patients is unclear. Purpose We investigated the rate of intracranial haemorrhage (ICH), major (MB) and gastrointestinal bleeding (GB) according to cancer types in AF patients. We also tested the predictive value of HAS-BLED, ATRIA and ORBIT bleeding risk scores. Methods Observational retrospective cohort study including 399,344 AF patients with cancer (mean age 77.9±10.2 years; 63.2% men). MB was defined according to Bleeding Academic Research Consortium (BARC) definitions. Results The highest ICH rates were found in leukaemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year) and pancreas cancer (1.41%/year). GBs were highest in liver (7.54%/year), pancreas (7.42%/year) and gastric (5.51%/year). Receiver operating characteristic (ROC) analysis showed that an ORBIT score ≥4 had the highest predictivity for MBs (AUC 0.805) followed by HAS-BLED and ATRIA (AUC 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for ICH (AUC 0.744 and 0.742, respectively), better than ATRIA (AUC 0.635). For GB, ORBIT ≥4 had the highest predictivity (AUC 0.756), followed by the HAS-BLED (AUC 0.702) and ATRIA (AUC 0.662). Conclusions Some cancer types carry a greater bleeding risk in AF patients. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up Conclusions Some cancer types carry a greater bleeding risk in AF patients. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up. Funding Acknowledgement Type of funding sources: None.

The effect of P2Y12 inhibitor monotherapy according to bleeding risk: a systematic review and meta-analysis

Abstract Background/Introduction P2Y12 inhibitor monotherapy is a promising novel strategy to reduce bleeding complications compared to DAPT. To determine which patients benefit most, we investigated the effect according to bleeding risk. Purpose The study aim was to analyse the safety and efficacy of P2Y12 inhibitor monotherapy versus dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients with and without high bleeding risk (HBR). Methods PubMed was searched for randomized clinical trials (RCTs) comparing P2Y12 inhibitor monotherapy to DAPT after PCI. Risk ratios (RR) and adjusted risk differences (ARD) of net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACCE) and major bleedings were calculated according to bleeding risk. Results Five RCTs including 31750 patients were selected. Monotherapy reduced major bleeding significantly in all patients (HBR: RR 0.63, 95% CI: 0.46 to 0.85; non-HBR: RR 0.58, 95% CI: 0.41 to 0.82) with a higher ARD in patients with HBR versus non-HBR. There was no difference between treatment effects on MACCE in both subgroups. Next to the expected higher number of bleeding events, we found an increase in MACCE in patients with HBR which resulted in a non-significant reduction of NACE (RR 0.89, 95% CI: 0.77 to 1.04). In patients without HBR, NACE was significantly reduced by monotherapy (RR 0.80, 95% CI: 0.67 to 0.96). Conclusions P2Y12 inhibitor monotherapy post PCI reduces bleeding complications without increasing ischemic events compared to DAPT, regardless of bleeding risk. HBR patients experience more bleeding and ischemic events without a net benefit of monotherapy. Funding Acknowledgement Type of funding sources: None.

Thirty-days versus standard duration of dual antiplatelet treatment after percutaneous coronary interventions: a systematic review and meta-analysis

Abstract Background/Introduction Abbreviation of duration of dual antiplatelet therapy (DAPT) (one or three months) has been recently proposed, especially for high-bleeding risk patients, after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Purpose The purpose of the specific systematic review and meta-analysis was to compare 30-days versus longer duration (≥3 months) of DAPT in patients undergoing PCI with DES, focusing on ischemic and bleeding events. Methods Three databases were screened for eligible randomized-control trials. The primary endpoint was the incidence of net adverse clinical events (NACE), as they were defined in each trial. Secondary endpoints consisted of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality, myocardial infraction, stroke, stent-thrombosis, repeat revascularization and major bleeding. Results We included 4 RCTs with a total of 26,576 patients; 13,282 patients were grouped in 30-days DAPT, while the remaining 13,294 were allocated in longer period of DAPT. One-month of DAPT did not significantly reduce NACE (odds ratio [OR]: 0.87, 95% confidence intervals [Cl]: 0.74–1.03); however major bleedings were significantly reduced by 22% (OR: 0.78, 95% Cl: 0.65–0.94). Mortality or ischemic events (stroke, myocardial infraction, revascularization and stent thrombosis) were not affected. Conclusions Thirty-days DAPT did not significantly affect NACEs. However, odds of major bleedings were reduced significantly by 22%. Mortality and ischemic events did not differ between the two arms. Thus, 30-days DAPT could be considered as a safe and feasible after PCI with DES in selected patients, especially those in high-bleeding risk. Forthcoming RCTs could shed light on the optimal duration of DAPT. Funding Acknowledgement Type of funding sources: None.

TCT-2 Two-Year Outcomes in High Bleeding Risk Patients With Bifurcations After Percutaneous Coronary Intervention and One Month of Dual Antiplatelet Therapy

TCT-2 Two-Year Outcomes in High Bleeding Risk Patients With Bifurcations After Percutaneous Coronary Intervention and One Month of Dual Antiplatelet Therapy

Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk

BackgroundThe optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear. ObjectivesThe objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction. MethodsIn the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. ResultsNACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; Pinteraction = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; Pinteraction = 0.72) with abbreviated APT. ConclusionsA 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)

Correlation Between the Japanese Version of the High Bleeding Risk (J-HBR) Criteria and the PRECISE-DAPT Score, and Optimal J-HBR Cut-Off Score to Predict Major Bleeding.

Background: The correlation between the Japanese version of high bleeding risk (J-HBR) criteria and the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score is unknown, as is the relationship of both risk scores with ischemic events.Methods and Results: This study enrolled 842 patients who underwent percutaneous coronary intervention (PCI) between January 2016 and December 2020. The 2 bleeding risk scores at the time of PCI and the subsequent risk of bleeding and ischemic events over a 1-year follow-up were examined. The J-HBR score was significantly correlated with the PRECISE-DAPT score (r=0.731, P<0.001). However, 1 year after PCI, the J-HBR was not significantly associated with the incidence of major bleeding and ischemic events (log-rank, P=0.058 and P=0.351, respectively), whereas the PRECISE-DAPT score predicted both the incidence of major bleeding and ischemic events (log-rank, P=0.006 and P=0.019, respectively). According to receiver operating characteristic curve analysis, a J-HBR score ≥1.5 was significantly associated with a higher cumulative incidence of major bleeding, but not ischemic events (log-rank, P=0.004 and P=0.513, respectively).Conclusions: The J-HBR score is highly correlated with the PRECISE-DAPT score. A J-HBR score ≥1.5 can identify high bleeding risk patients without an increased risk of ischemic events.

Optimal Antithrombotic Therapy in Patients Undergoing Percutaneous Coronary Intervention: A Focused Review on High Bleeding Risk.

Dual antiplatelet therapy (DAPT) is a therapeutic cornerstone to prevent stent thrombosis following percutaneous coronary intervention (PCI) for coronary artery disease (CAD). However, the longer the DAPT duration, the higher the incidence of bleeding and mortality. Since the advent of second-generation drug-eluting stents (DES), the continuous evolution of DES has reduced the thrombotic risk and allowed for a shorter DAPT duration. On the other hand, concerns on the elevated risk of bleeding during antithrombotic therapy have been further raised due to the growing number of elderly CAD patients with multiple comorbidities. The consequent debate topic over post-PCI antithrombotic therapy has shifted from simply reducing thrombotic risk to safely minimizing bleeding risk. Due to the significant impact of bleeding on clinical outcomes, including prognosis, current guidelines on antithrombotic therapy for CAD prioritize stratification of patients at a high bleeding risk (HBR) as the top consideration in determining post-PCI antithrombotic therapy. Achieving optimal antithrombotic therapy for each patient undergoing PCI requires a better understanding of the clinical variables constituting the balance of bleeding and thrombotic risk. This review highlights relevant evidence required to optimize antithrombotic therapy for HBR patients undergoing PCI.

Vascular healing in high-bleeding-risk patients at 3-month after everolimus-eluting stent versus biolimus A9-coated stent implantation: insights from analysis of optical coherence tomography and coronary angioscopy.

The prevalence of high-bleeding-risk (HBR) patients who undergo coronary stenting has been reported as 20-40%. This study sought to assess vascular healing in HBR patients by coronary angioscopy (CAS) and optical coherence tomography (OCT). We prospectively analyzed 38 HBR patients with coronary artery disease who successfully underwent everolimus-eluting stent (EES) implantation (20 patients, 23 lesions) or drug-coated stent (DCS) implantation (18 patients, 18 lesions). Follow-up coronary angiography, CAS, and OCT were planned at 3months after the procedure. The clinical characteristics and inclusion criteria of HBR were comparable between groups. CAS analysis showed that mean yellow color grade was significantly higher with EES than with DCS (1.33 [1.0, 1.67] vs. 1.0 [0.67, 1.5]; P = 0.04). In contrast, OCT analysis demonstrated that most struts in both groups were well-apposed struts with neointimal coverage (93.9% each; P = 1.00), and percentages of the mean neointimal area were comparable between EES and DCS (4.4 ± 3.5mm2 vs. 4.5 ± 4.1mm2; P = 0.91). The frequency of uncovered struts was significantly lower with EES than with DCS (2.4% vs. 5.3%; P < 0.001), whereas the frequency of malapposed struts was significantly higher with EES than with DCS (3.5% vs. 0.8%; P < 0.001). During follow-up, no stent thrombosis or major bleeding complications were encountered in either group. Among HBR patients, both EES and DCS demonstrated good vascular healing at 3-month follow-up with some different features in CAS and OCT assessments.

Impact of Medication Nonadherence in a Clinical Trial of Dual Antiplatelet Therapy

BackgroundNonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials. ObjectivesThe purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial. MethodsAt 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3. ResultsIn total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation. ConclusionsIn the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)

Temporal Trends in the Prevalence, Treatment and Outcomes of Patients with Acute Coronary Syndrome at High Bleeding Risk.

(1) Background: High bleeding risk is associated with adverse outcomes in ACS patients. We aimed to evaluate temporal trends in treatment and outcomes of ACS patients according to bleeding risk. (2) Methods: Included were ACS patients enrolled in ACSIS surveys. Patients were divided into three groups according to enrolment period: early (2002–2004), mid (2006–2010) and recent (2012–2018). Each group was further stratified into three subgroups according to CRUSADE bleeding risk score. The primary endpoints were 30-day MACE and 1-year all-cause mortality. (3) Results: Included were 13,058 ACS patients. High bleeding risk patients were less frequently treated with guideline-based medications and coronary revascularization. They also had higher rates of 30-day MACE and 1-year all-cause mortality regardless of the enrollment period. Among patients enrolled in early period, 30-day MACE rates were 10.8%, 17.5% and 24.3% (p < 0.001) and 1-year all-cause mortality rates were 2%, 7.7% and 23.6% (p < 0.001) in the low, moderate and high bleeding risk groups, respectively. Among patients enrolled in mid period, 30-day MACE rates were 7.7%, 13.4% and 23.5% (p < 0.001) and 1-year all-cause mortality rates were 1.5%, 7.2% and 22.1% (p < 0.001) in low, moderate and high bleeding risk groups, respectively. For patients enrolled in recent period, 30-day MACE rates were 5.7%, 8.6% and 16.2%, (p < 0.001) and 1-year all-cause mortality rates were 2.1%, 6% and 22.4%, (p < 0.001) in low, moderate and high bleeding risk groups, respectively. These differences remained significant following a multivariate analysis. (4) Conclusions: The percentage of patients at high bleeding risk has decreased over the last years. Despite recent improvements in the treatment of ACS patients, high bleeding risk remains a strong predictor of adverse outcomes.

Correction to: One-Month Dual Antiplatelet Therapy After Bioresorbable Polymer Everolimus-Eluting Stents in High Bleeding Risk Patients.

Correction to: One-Month Dual Antiplatelet Therapy After Bioresorbable Polymer Everolimus-Eluting Stents in High Bleeding Risk Patients.

Duration of antiplatelet therapy after complex percutaneous coronary intervention in patients at high bleeding risk: a MASTER DAPT trial sub-analysis

To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Antiplatelet Therapy in High-Bleeding Risk Patients Undergoing PCI: Walking a Tightrope.

Historically, prevention from ischemic events with dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI) took precedence over protection from bleeding. However, increasing data suggest that major bleeding complications are as detrimental as ischemic events. Awareness about the prognostic impact of bleeding prompted the search for new strategies aimed at maximizing both ischemic and bleeding protection. This is noteworthy because patients at high bleeding risk (HBR) have generally been underrepresented in clinical trials on DAPT and they often are at increased risk of ischemic events as well. The present review discusses the evidence base for new pharmacotherapeutic strategies to decrease bleeding risk without compromising ischemic protection among HBR patients undergoing PCI, including shortening DAPT duration, early aspirin withdrawal, and inhibitor de-escalation.