Abbreviated or standard antiplatelet therapy after PCI in HBR patients with chronic kidney disease: aprespecified analysis from the MASTER DAPT trial.

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

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.

330 INTRAVENOUS CANGRELOR INFUSION IN HIGH BLEEDING RISK PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: PRELIMINARY RESULTS OF THE ICARUS REGISTRY

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.

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.

Recurrent Events Analysis of MASTER DAPT: Total Ischemic and Bleeding Events After Abbreviated vs Prolonged DAPT in 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.

P297 INTRAVENOUS CANGRELOR INFUSION IN HIGH BLEEDING RISK PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: PRELIMINARY RESULTS OF THE ICARUS REGISTRY

The benefits of de-escalation of P2Y12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status. We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status. This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria. A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84). In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y12 inhibition on reducing haemorrhagic events was greater in patients with HBR.

Introduction: Prognosis in high-bleeding risk (HBR) patients after percutaneous coronary intervention (PCI) is largely dependent on risk of ischemic/bleeding events. Inflammation is known to increase the ischemic risk following PCI in the general population, yet its impact on HBR patients remains unknown. Hypothesis: We assessed the hypothesis that inflammation, as reflected by elevated high-sensitivity C - reactive protein (hsCRP), increases the risk of ischemic and bleeding events in HBR patients undergoing PCI. Methods: We included patients who underwent PCI at a tertiary care center between 2014 and 2017. Patients were classified as HBR if they met ≥1 major or ≥2 minor criteria according to the Academic Research Consortium (ARC)-HBR consensus. Patients were then stratified into high (≥3 mg/l) and low (&lt;3 mg/ml) baseline hsCRP level; those presenting with myocardial infarction (MI) or hsCRP &gt;10 mg/l were excluded. The main outcomes of interest were major adverse cardiac events (MACE) (composite of all-cause death, MI, and target vessel revascularization) and bleeding events. Results: Out of 7,186 patients included, 3,403 (42.3%) fulfilled the ARC-HBR definition of whom 1,046 (34.4%) had high hsCRP. These patients were frequently female, younger, and had more cardiovascular risk factors (diabetes, kidney disease, and peripheral artery disease) yet similar angiographic features (multivessel disease, syntax score, and lesion length) than those with low hsCRP. Although risk of MACE at 1 year was similar in HBR patients with either high or low hsCRP, mortality risk was significantly higher in the former group ( Figure 1 ). In addition, HBR patients with high hsCRP were more likely to have periprocedural bleeding (OR 1.72, 95% CI [1.14-2.58], p=0.01) but similar risk of 1-year major bleeding as HBR patients with low hsCRP ( Figure 1 ). Conclusion: In conclusion, inflammation is associated with periprocedural bleeding and 1-year mortality in HBR patients undergoing PCI.

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

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

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.

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.

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