Do we still need more data to adopt a short duration of DAPT routinely following PCI in high bleeding risk patients?

Whether the underlying risk of bleeding influences the associations between patterns of dual antiplatelet therapy (DAPT) cessation and adverse events after percutaneous coronary intervention is unknown. Patients enrolled in the prospective, international, multicenter PARIS registry (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) were categorized according to their risk of bleeding using the PARIS bleeding risk score. We evaluated the incidence, patterns, and association between modes of DAPT cessation and outcomes across bleeding risk groups. Modes of DAPT cessations were defined as physician-guided DAPT discontinuation, brief interruption (<14 days) or disruption for bleeding, or noncompliance. The primary end point of interest was major adverse cardiac events, defined as the composite of cardiac death, myocardial infarction, or definite-probable stent thrombosis. From a total of 5018 patients, 513 (10.2%) were classified as high, 2058 (41.0%) as intermediate, and 2447 (48.8%) as low risk for bleeding. High bleeding risk (HBR) patients were older and had greater prevalence of comorbidities. Compared with non-HBR, HBR patients had higher rates of both ischemic and bleeding events. The cumulative incidence of DAPT cessation was higher in HBR patients, mostly driven by physician-guided discontinuation and disruption. Of note, DAPT disruption occurred in 17.7%, 10.4%, and 7.8% at 1 year and 22.0%, 15.1%, and 12.0% at 2 years (P<0.0001) in high, intermediate, and low bleeding risk groups, respectively. Physician-guided DAPT discontinuation was not associated with increased risk of major adverse cardiac events in both HBR and non-HBR patients, while DAPT disruption was associated with an increased risk of major adverse cardiac events across all bleeding risk groups. There was no interaction between bleeding risk status and clinical outcomes for any cessation mode. Patients at HBR remain at higher risk of adverse events. Disruption of DAPT is associated with an increased risk of major adverse cardiac events irrespective of the underlying bleeding risk. Physician-guided discontinuation of DAPT appears to be safe, irrespective of HBR.

Coronary artery disease (CAD) is one of the leading causes of death in our patient population. In the era of cardiovascular intervention, Percutaneous coronary intervention (PCI) is one of the most important modalities in treating these group of patients. Several CAD risks factors and co-morbid conditions are key responsible factor of procedural success. High bleeding risk (HBR) patients undergoing PCI is not an uncommon phenomenon. Incidences and prevalence of HBR patients with CAD and their management by PCI is not well addressed in our literature. PCI in HBR patients carries potential risk of intracranial hemorrhage (ICH) and lifethreatening bleeding. Therefore, careful pre-PCI assessment of possible risk or threats of post-PCI complications in patients with HBR are deem necessitate to understand. We recommend forming multicenter common consensus and to form a guideline in treating HBR patient by PCI. Thus, to reduce post procedural complication and subsequent improvement of mortality and morbidity in HBR patients undergoing PCI in both ST segment elevated myocardial infarction (STEMI) and as well as non-STEMI. Bangladesh Heart Journal 2021; 36(2): 133-138

ObjectivesIn an all-comers cohort undergoing percutaneous coronary intervention (PCI), we aimed to assess prevalence of high bleeding risk (HBR) patients and impact of HBR and dual antiplatelet therapy (DAPT) on clinical events. BackgroundHBR represents a complex subgroup of patients undergoing PCI. MethodsIn the ReCre8 trial, patients undergoing PCI were stratified for troponin status and diabetes and randomized to a permanent polymer zotarolimus-eluting- or polymer-free amphilimus-eluting stent. Patients were treated with 12 months (troponin-positive) or one month (troponin-negative) of DAPT. We evaluated clinical outcomes in patients with and without HBR according to the Academic Research Consortium for High Bleeding Risk criteria. ResultsFrom a total of 1488 patients included in this subanalysis, 406 patients (27.3 %) were identified as being at HBR. Among HBR patients, target-lesion failure (TLF) was similar after one year yet was higher after three years (13.3 % vs. 9.1 %; p = 0.013), compared to non-HBR patients. There was no difference in Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding, however BARC 2 to 5 bleeding was higher after three years with 4.9 % vs. 3.0 % (p = 0.037). There were no differences between troponin-positive (12-months DAPT) and -negative (1-month DAPT) HBR patients with respect to ischemic and bleeding outcomes. ConclusionsIn this all-comers population of PCI patients, a higher TLF rate among HBR patients at long-term follow-up was found, underlining the complexities involving treatment of HBR patients. We did not observe statistically significant differences in BARC 3 to 5 bleeding between HBR and non-HBR patients regardless of DAPT duration. Clinical trial registrationURL: http://www.clinicaltrials.gov, unique identifier: NCT02328898.

High bleeding risk patients with acute coronary syndromes treated with contemporary drug-eluting stents and Clopidogrel or Ticagrelor: Insights from CHANGE DAPT

Abbreviated or Standard Antiplatelet Therapy After PCI in Diabetic Patients at High Bleeding Risk

The balance between thrombotic and bleeding risk is of great concern in high bleeding risk (HBR) patients. This study evaluated the relationship between perioperative antiplatelet reactivity and thrombotic and bleeding events in patients at HBR undergoing percutaneous coronary intervention (PCI).Methods and Results: In this post hoc analysis of the PENDULUM (Platelet rEactivity in patieNts with DrUg eLUting stent and balancing risk of bleeding and ischeMic event) registry, patients undergoing PCI were categorized as HBR or non-HBR, and stratified as having high platelet reactivity (HPR; P2Y12reaction unit [PRU] >208) or non-HPR (PRU ≤208). Cumulative incidences of cardiovascular and cerebrovascular events (Journal of the American College of Cardiology expert definitions) and bleeding events (Bleeding Academic Research Consortium criteria) were assessed 12 months after index PCI. The incidence of ischemic and bleeding events was ~3-fold higher in HBR vs. non-HBR patients. Thrombotic/ischemic events were significantly more common in the HPR subgroup in HBR patients (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.28; P=0.012), but there was no difference in non-HBR patients. After adjustment for covariates, HPR in HBR patients remained an independent factor for thrombotic and ischemic events (HR: 1.69; 95% CI: 1.13-2.54; P=0.011), but not for bleeding events (HR: 1.56; 95% CI: 0.78-3.11; P=0.210). Maintaining adequate PRU levels during PCI is an important factor in improving clinical outcomes, especially for HBR patients.

Data on ischemic and bleeding outcomes after percutaneous coronary intervention (PCI) in high bleeding risk (HBR) patients with chronic kidney disease (CKD) are scarce. We aimed to evaluate the association between CKD and ischemic and bleeding outcomes in HBR patients who underwent PCI. Among 10,502 patients in the four post-approval registries evaluating patients undergoing PCI, 2,300 patients presented with at least one major or two minor ARC-HBR criteria. CKD was defined as eGFR < 60mL/min/1.73m2. These HBR patients were divided into 3 groups: eGFR < 30mL/min/1.73m2 defined as severe CKD (N = 221), eGFR 30- < 60mL/min/1.73m2 defined as moderate CKD (N = 970), eGFR ≥ 60mL/min/1.73m2 defined as no CKD (N = 1,109). The primary endpoint was the composite of cardiac death, myocardial infarction, or stent thrombosis, and the safety endpoint was major bleeding up to 4-year follow-up. HBR patients with CKD were more often female and had higher rates of comorbidities compared to those without CKD. Reduced renal function was associated with higher rates of the primary endpoint (severe CKD vs. moderate CKD vs. no CKD: 30.2% vs. 12.5% vs. 9.1%, P < 0.01) as well as major bleeding (10.3% vs. 8.9% vs. 6.4%, P = 0.03). After adjustment, severe CKD and moderate CKD in HBR patients remained independent predictors for the primary endpoint (HR [95%CI] 2.84 [1.94-4.16], P < 0.01, 1.48 [1.10-2.00], P < 0.01) compared to those with no CKD. However, decreased renal function was no longer significantly associated with major bleeding after adjustment. In conclusions, in HBR patients undergoing PCI, CKD has an important impact on major ischemic events after PCI.

To explore the impact of 6- versus 12-month dual antiplatelet therapy (DAPT) on the clinical prognosis of high bleeding risk (HBR) patients. The optimal DAPT duration after percutaneous coronary intervention (PCI) in HBR patients is unclear. This study is a post hoc analysis of the 4-year clinical follow-up results of the I LOVE IT 2 study. Prevalence and prognosis of HBR patients were explored, and clinical outcomes of HBR patients who underwent 6- versus 12-month DAPT were compared. The primary outcome was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The secondary outcomes were BARC type 2-5 bleeding and net clinical adverse events (NACE), defined as a composite of all-cause death, myocardial infarction (MI), ischemia-driven revascularization, stroke, stent thrombosis, or any bleeding events. HBR occurred in 440 of 2,737 patients (16.0%). HBR patients were associated with a higher risk of BARC type 3 or 5 bleeding (2.95 vs. 1.52%, p = .03), NACE (31.82 vs. 25.99%, p = .01), all-cause death (5.68 vs. 3.13%, p = .008) and stroke (9.09 vs. 3.83%, p < .001) than non-HBR patients at 4 years. There were no significant differences in BARC type 3 or 5 bleeding (3.07 vs. 2.76%, p = 1.00) or NACE rate (31.9 vs. 33.8%, p = .72) between patients who underwent 6- and 12-month DAPT. HBR patients are at a higher risk of long-term bleeding and ischemic events than non-HBR patients. The safety and efficacy of 6- and 12-month DAPT were comparable in HBR patients.

Introduction: Conventional PCI with stenting in high bleeding risk (HBR) patients is associated withhigher all-cause mortality rates and bleeding complications. To minimize DAPT duration, stentlessPCI using drug-coated balloons (DCB) is increasingly favored. However, there is a lack ofcomprehensive long-term outcome data on stentless therapy in HBR patients within real-worldclinical practice. Research Questions: Do discernible disparities exist in the extended-term ramifications of stentless treatment utilizing DCB between patients classified as having HBR and those without in clinical practice? Methods: We incorporated patients who underwent stentless PCI employing DCB for de novo lesions at our medical facility from January 2015 to December 2021. Exclusion criteria encompassedpatients presenting with acute coronary syndromes. The primary outcome measure was defined as all-cause mortality, whereas the secondary outcome measure focused on bleeding events as per thedefined criteria of BARC bleeding grades 3 or 5. Patients were stratified into two cohorts based on the ARC-HBR criteria and subsequently subjected to comparative analysis utilizing Cox proportional hazards regression analysis. Results: A total of 392 patients were included, including a mean age of 70 ± 11 years and 46% male. Of these patients, 62% had HBR, and the procedure's success rate was 99.7%. Over a median follow-up period of 24 months, 29 patients (7.4%) experienced all-cause mortality. HBR patients showed significantly higher blood BNP levels compared to non-HBR patients (median [IQR]: 85pg/mL [36-226] vs. 27 pg/mL [15-49], p&lt;0.01). After adjusting for blood BNP levels, the hazard ratio for all-cause mortality in HBR patients was 4.06 [1.18-14.00], indicating a 4-fold higher risk compared to non-HBR patients (p=0.03). Among the cohort, 12 individuals (1.8%) experienced BARC grades 3 or 5 bleeding events, with a tendency towards a greater occurrence in the HBRpatient group (adjusted HR: 2.26 [0.46-11.20], p=0.32), although the difference was not significant. Conclusions: The findings further indicate that patients with HBR exhibit a propensity for inferior long-term outcomes relative to non-HBR patients in stentless treatment with DCB in the real world.

Background: Managing thrombotic and hemorrhagic risks associated with dual antiplatelet therapy (DAPT) in patients with a high bleeding risk (HBR) is challenging, especially in post-percutaneous coronary intervention (PCI) patients. Transitioning from DAPT to single antiplatelet therapy (SAPT) aims to reduce bleeding complications while ensuring sufficient ischemic protection. This study explored Indian interventional cardiologists’ views on de-escalation strategies in HBR patients, considering bleeding risk factors, including Indian-specific risks, such as tropical diseases and other comorbidities.Materials and methods: A cross-sectional questionnaire-based survey was conducted from June 2024 to July 2024 among 400 interventional cardiologists in India. A structured, pre-validated questionnaire was used to gather data on the perceived prevalence of HBR in routine practice, key HBR factors specific to Indian patients (such as frailty, comorbidities, and tropical diseases), preferred SAPT agents after DAPT, perceived bleeding risk profiles of antiplatelet agents, and barriers to implementation of de-escalation. Participation was voluntary and anonymous. Responses were analyzed using descriptive statistics and reported as frequencies and proportions.Results: Of the 375 interventional cardiologists, 193 (51.47%) reported an HBR prevalence of less than 10%, and 250 (66.67%) believed that gastrointestinal (GI) bleeding was the most common complication in patients receiving DAPT. The main HBR factors included frailty, reported by 326 (86.90%) cardiologists, chronic kidney disease (CKD) stage 3 or severe, reported by 319 (85.1%) cardiologists, and liver cirrhosis with portal hypertension, reported by 324 (86.4%) interventional cardiologists. After DAPT, 128 (34.13%) cardiologists preferred clopidogrel 75 mg, and 107 (28.53%) preferred aspirin 75 mg. Clopidogrel was seen as the least likely to cause bleeding by 179 (48.00%) interventional cardiologists, with 80 (21.33%) rating it as the best option for HBR patients de-escalating from DAPT to SAPT.Conclusions: This study presents Indian interventional cardiologists’ perspectives on de-escalation strategies, including transitioning from DAPT to SAPT, to reduce bleeding complications, while ensuring adequate ischemic protection in patients with HBR post-PCI. Interventional cardiologists have outlined criteria for identifying critical HBR factors relevant to the Indian population. Clopidogrel was the most preferred medication for transitioning to SAPT in HBR patients. Simplified Indian bleeding risk scoring tools and tailored approaches are essential for improving DAPT management in patients with HBR.

BackgroundTo date, it has not been ascertained whether shortening the duration of dual antiplatelet therapy (DAPT) can benefit high bleeding risk (HBR) patients. This systematic review and meta-analysis was performed to investigate the safety and efficacy of short (≤ 3 months) DAPT in HBR patients after percutaneous coronary intervention (PCI).MethodsThe PubMed, Embase, and Clinical Trials databases were searched from inception until November 2021 to identify studies that evaluated the safety and efficacy of short DAPT in HBR patients implanted with new-generation drug-eluting stents (DES). Primary endpoints included major bleeding, definite or probable stent thrombosis (ST), and myocardial infarction (MI), while secondary endpoints included all-cause death and ischemic stroke. Based on the fixed and random effect model, the risk ratio (RR) and 95% confidence interval of each endpoint were measured.ResultsFive observational studies and one randomized controlled trial were included, involving 15,432 HBR patients. Short DAPT for HBR patients undergoing PCI had a lower incidence of major bleeding in comparison with standard (> 3 months) DAPT (2.3% vs. 3.2%, RR 0.64 [0.44, 0.95], p = 0.03), while short DAPT was comparable to standard DAPT with regard to definite or probable ST (0.4% vs. 0.3%, RR 1.31 [0.77, 2.23], p = 0.32) and MI (2.4% vs. 2.0%, RR 1.17 [0.95, 1.45], p = 0.14).ConclusionsAmong HBR patients implanted with new-generation DES, short DAPT was associated with reduced risk of major bleeding without significantly increasing the risk of definite or probable ST and MI in comparison with standard DAPT.

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 &amp;lt;25, patients were categorised accordingly, and a maximum score of ≥25 and minimum score of &amp;lt;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&amp;lt;0.001), elderly (median age 75 [IQR 67, 81] vs. 57 years [IQR 51, 64], p-value&amp;lt;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&amp;lt;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.

The distal radial access (DRA), a potential alternative to the trans-radial approach (TRA), may offer advantages in terms of access site complications due to its smaller vessel diameter, especially for high bleeding risk (HBR) patients. This study aims to investigate the feasibility of DRA in HBR patients. Based on data from the KODRA registry, a prospective, multicenter cohort, this study analyzed 1,586 patients who underwent successful percutaneous coronary intervention (PCI) via DRA. Patients were categorized into HBR and non-HBR groups. The primary endpoint of the study is DRA-related bleeding, and the secondary endpoints of the study are overall access site complications and each component of the access site complications. To reduce the effect of potential confounders, a multivariable adjustment analysis was performed. The mean age of the total population was 71.1±10.8 years, and 40.3% of patients were female. Both DRA-related bleeding (odds ratio [OR], 1.15; 95% confidence interval [CI], 0.67-1.97; p=0.616) and overall access site complications (OR, 1.08; 95% CI, 0.67-1.72; p=0.761) were not significantly different between the HBR group and non-HBR group after multivariable adjustment. No major bleeding before discharge was observed in both groups. Furthermore, the incidence of distal and conventional radial artery occlusion was less than 1% at 1-month follow-up in both groups. Our study results showed the safety of DRA for both DRA-related bleeding and access site complications among HBR patients who underwent PCI. ClinicalTrials.gov Identifier: NCT04080700.

Abbreviated antiplatelet therapy (APT) can reduce bleeding without increasing ischaemic harm in high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI). The impact of chronic kidney disease (CKD) on the safety and effectiveness of abbreviated APT remains unknown. We aimed to investigate the comparative effectiveness of abbreviated (1 month) versus standard (≥3 months) APT in HBR patients with and without CKD. This was a prespecified analysis from the MASTER DAPT trial, which randomised 4,579 HBR patients (1,428 [31%] with CKD) to abbreviated or standard APT. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Co-primary outcomes were net adverse clinical events (NACE; a composite of all-cause death, myocardial infarction [MI], stroke, and major bleeding), major adverse cardiac or cerebral events (MACCE; all-cause death, MI and stroke), and Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 11 months. NACE did not significantly differ with abbreviated and standard APT among CKD patients (hazard ratio [HR] 0.91, 95% confidence interval [CI]: 0.66-1.24) and non-CKD patients (HR 0.96, 95% CI: 0.73-1.27; pinteraction=0.78). Similarly, MACCE did not differ in CKD patients (HR 0.91, 95% CI: 0.64-1.27) and non-CKD patients (HR 1.09, 95% CI: 0.78-1.51; pinteraction=0.45). Abbreviated APT was associated with consistently lower BARC 2, 3, or 5 bleeding in both patients with CKD (HR 0.74, 95% CI: 0.52-1.07) and without it (HR 0.66, 95% CI: 0.51-0.85; pinteraction=0.59). Abbreviated APT was associated with similar NACE and MACCE rates and reduced bleeding compared with standard APT in HBR patients undergoing PCI, regardless of the presence or absence of CKD. (ClinicalTrials.gov: NCT03023020).

MAPT (Mono Antiplatelet Therapy) as Regular Regimen After COBRA PzF™ NanoCoated Coronary Stent (NCS) Implantation