Endpoint Of Bleeding Research Articles

Abstract 4124335: Ticagrelor monotherapy the way forward after Percutaneous Coronary Interventions : An updated meta-analysis

Background: With the advent of newer generation drug eluting stents, the chorus for shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary interventions (PCI) is getting louder and louder. Ticagrelor monotherapy after a short course of DAPT has been studied in a few randomized controlled trials with promising results. We conducted a systematic review and meta-analysis comparing the ticagrelor monotherapy with DAPT after short duration DAPT in patients undergoing PCIs. Methods: PubMed, Embase and Cochrane databases were searched for RCTs comparing ticagrelor monotherapy to DAPT after PCI and reported the outcomes of Major Adverse Cardiac Events including death, myocardial infarction or stroke (MACE); Major Adverse Cardiac and Cerebrovascular Events including death, myocardial infarction, stroke, stent thrombosis or target vessel revascularization (MACCE); Major bleeding; Death from any cause; CV death; Stent thrombosis and Target vessel revascularization (TVR). Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Statistical analysis was performed using Review Manager Web (Cochrane Collaboration). Heterogeneity was examined with I 2 test. Results: Out of 3208 database results, 5 RCTs with 32,393 patients were included; 16,188 (50%) received Ticagrelor monotherapy. Studies had mean follow-up ranging from 12 months to 24 months. Baseline characteristics are as per Table 1. Safety endpoints of major bleeding (HR 0.50; 95% CI 0.38-0.66; p < 0.0001; I 2 = 23 %; Figure 1A), was significantly less with ticagrelor monotherapy. Efficacy endpoints of MACE, MACCE, Death from any cause, CV Death, target vessel revascularization (TVR) and stent thrombosis were not significantly different between ticagrelor and DAPT (Figure 1 and 2). Conclusion: Ticagrelor monotherapy reduces major bleeding as compared to continued DAPT for 12 months after PCI. Major ischemic outcomes were similar in both groups. Ticagrelor monotherapy may be the way forward after short duration of DAPT in patients undergoing PCI.

Invasive Versus Conservative Strategy in Older Adults ≥75 Years of Age With Non-ST-segment-Elevation Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Older adults with non-ST-segment-elevation acute coronary syndrome are less likely to undergo an invasive strategy compared with younger patients. Randomized controlled trials traditionally exclude older adults because of their high burden of geriatric conditions. We searched for randomized controlled trials comparing invasive versus medical management or a selective invasive (conservative) strategy for older patients (age≥75 years) with non-ST-segment-elevation acute coronary syndrome. Fixed effects meta-analysis was conducted to estimate the odds ratio (OR) with 95% CI for the composite of death or myocardial infarction (MI) and individual secondary end points of all-cause death, cardiovascular death, MI, revascularization, stroke, and major bleeding. Nine studies with 2429 patients (invasive: 1228 versus control: 1201) with a mean follow-up of 21 months were included. An invasive strategy was associated with a significantly decreased risk of a composite of death and MI (OR, 0.67 [95% CI, 0.54-0.83], P<0.001), MI (OR, 0.56 [95% CI, 0.45-0.70], P<0.001) and subsequent revascularization (OR, 0.27 [95% CI, 0.16-0.48], P<0.001). There was no difference in all-cause death (OR, 0.84 [95% CI, 0.65-1.10], P=0.21), cardiovascular death (OR, 0.85 [95% CI, 0.63-1.15], P=0.30), stroke (OR, 0.74 [95% CI, 0.38-1.47], P=0.39), or major bleeding (OR, 1.24 [95% CI, 0.42-3.66], P=0.70). In older patients ≥75 years old with non-ST-segment-elevation acute coronary syndrome, an invasive strategy reduced the risk of a composite of death and MI, MI, and subsequent revascularization compared with a conservative strategy alone. Older adults with higher burden of geriatric conditions should be included in future trials to improve generalizability to this growing population.

Association of P2Y12 inhibitor pretreatment strategy with short and long term ischemic and bleeding outcomes in NSTE-ACS patients

Abstract Background and Aims Oral P2Y12 inhibitors form the basis of both short and long term antiplatelet therapy in NSTE-ACS patients. While reducing thrombogenic activity and ischemic risk is the basis of routine P2Y12 inhibitor pretreatment in NSTE-ACS patients, timing of treatment became controversial as a result of studies showing routine P2Y12 inhibitor pretreatment is associated with an increased risk of bleeding. Even though routine pretreatment is no longer recommended in the ESC guidelines, the inadequacies in RCTs combining all treatment modalities have been noted. Our study aims to determine the relationship between P2Y12 inhibitor pretreatment strategy and short and long-term ischemic and bleeding events. Methods The study was designed as a single-center, prospective and observational study. 2602 patients, aged between 18 and 85, diagnosed with NSTE-ACS in accordance with ESC guidelines were included in the study. 2189 patients were administered with P2Y12 inhibitor pretreatment while 413 patients weren't. Demographic data, CVD risk factors, ECG, echocardiography and laboratory findings at the time of admission, interventional procedural details, type of antiplatelet and anticoagulant treatment and application time were recorded. Patients were divided into two groups as pretreatment and no-pretreatment according to the time of administration of P2Y12 inhibitor loading dose. In the no-pretreatment group choice of P2Y12 inhibitor was left to operator in the cath lab before proceeding to PCI. Post-procedural in-hospital and long term follow up (1 year) were obtained through hospital and national registry systems and patient survey. Results In the no-pretreatment group 91.3% of patients underwent coronary angiography and PCI was performed in 51.8%. In patients proceeding to PCI, 58.5% were given clopidogrel and 41.5% were given a potent P2Y12 inhibitor. In the pretreatment group, clopidogrel was the drug of choice in 93.8% of patients. In the pretreatment group, the primary composite endpoint (MACE and bleeding events) were more common during in-hospital follow-up and this difference was due to a significant increase in both BARC class I &amp; II and class III, IV &amp; V bleedings (Table 1). In the long-term follow up, statistically significant difference was only seen in BARC class I &amp; II bleedings in the pretreatment group. There were no difference in MACE rates in neither in-hospital or long-term follow up (Table 2). Also in multivariate regression analysis, pretreatment with a P2Y12 inhibitor was found to be an independent predictor of short term primary composite endpoints and long-term all-cause mortality. Conclusion The results of our study investigating the effects of the P2Y12 inhibitor pretreatment strategy on ischemic and bleeding endpoints in NSTE-ACS patients showed that the pretreatment strategy did not lead to an improvement in MACE rates in in-hospital and long-term follow-up but caused on overall increase in bleeding events.Kaplan-Meier Survival Analysis

Short versus conventional DAPT in patients undergoing PCI with ultra-thin DES by renal function: an analysis from the HOST-IDEA trial

Abstract Background Patients with impaired renal function are known to have an elevated risk of both ischemic and bleeding events following percutaneous coronary intervention (PCI). However, there is insufficient data available on the optimal duration of dual antiplatelet therapy (DAPT), especially with the latest generation of drug-eluting stent (DES)s. Objective We investigated to assess the efficacy and safety of abbreviated duration of DAPT in patients undergoing PCI with 3rd generation DESs based on their renal function. Methods In this prespecified subgroup analysis of the HOST-IDEA trial, a total of randomized 1997 patients with available baseline estimated glomerular filtration rate (eGFR) were categorized into three groups: high eGFR (&amp;gt;90 mL/min), intermediate eGFR (60 to 90 mL/min), and low eGFR (&amp;lt;60 mL/min). The primary outcome assessed during the 1-year follow-up period was net adverse clinical events (NACE). Ischemic and bleeding endpoints were also evaluated. Results Compared to intermediate or high eGFR groups, the low eGFR group resulted in significantly worse outcomes (P &amp;lt; 0.001). 3-6 month DAPT was associated with similar risk of NACE across all eGFR groups (High eGFR: HR: 0.91; 95% CI: 0.38-2.20; Intermediate eGFR: HR: 0.76; CI: 0.33-1.73; Low eGFR: HR: 0.99; CI: 0.51-1.92). There was also no significant difference in target lesion failure (HR: 0.95; CI: 0.32-2.83, HR: 0.77; CI: 0.29-2.06, and HR: 1.14; CI: 0.47-2.75) and major bleeding (HR: 0.84; CI: 0.19-3.74, HR: 0.59 CI: 0.14-2.48; and HR 0.83 CI: 0.34-2.05) among all stratified eGFR groups. This effect was also consistent in patients of end stage of renal disease (eGFR &amp;lt;15 mL/min). Conclusions In patients undergoing PCI with third generation DESs, short DAPT was comparable to conventional DAPT regardless of their baseline renal function.

Efficacy and safety of long-term edoxaban treatment for low body weight cancer patients with isolated distal deep vein thrombosis: a post-hoc subgroup analysis of the ONCO DVT study

Abstract Background Low body weight is known to be a bleeding risk in the anticoagulation treatment. ONCO DVT study revealed that 12-month edoxaban treatment for cancer patients with isolated distal deep vein thrombosis (DVT) reduced a composite outcome of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death compared with 3-month edoxaban treatment. However, the efficacy and safety of long-term edoxaban treatment for cancer patients with low body weight is unclear. Purpose In this subgroup analysis, we assessed the efficacy and safety of 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT. Methods We conducted a post-hoc subgroup analysis of the ONCO DVT study in the low body weight patients. ONCO DVT study was a multicenter, open-label, adjudicator-blinded, randomized clinical trial. Cancer patients with isolated distal DVT were assigned to 12-month or 3-month edoxaban treatment. The primary endpoint was a composite outcome of a symptomatic recurrent VTE or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months. We enrolled patients who met low body weight defined in Japanese Version of High Bleeding Risk criteria (&amp;lt;55 kg for men, &amp;lt;50 kg for women) and evaluated the efficacy and safety of 12-month edoxaban treatment using logistic regression models and log-rank test. Results Among 601 patients in the intention-to-treat population of ONCO DVT study, 322 patients (53.6%) met low body weight: 151 patients were in 12-month edoxaban group and 171 patients were in 3-month edoxaban group. The body weight was similar between two group (47.1±5.2 kg in 12-month edoxaban group vs. 46.9±5.4 kg in 3-month edoxaban group; P=0.77). All of them used a lower dose edoxaban (30 mg once daily) following the dose reduction criteria. 12-month edoxaban group had lower rates of the primary endpoint compared with 3-month edoxaban group (2 patients (1.3%) vs. 10 patients (5.8%); Odds ratio 0.22 [95% CI, 0.05–1.00]; Log-rank P=0.036). There was no significant difference in the major secondary endpoint of major bleeding (12 patients (7.9%) in 12-month edoxaban group vs. 16 patients (9.4%) in 3-month edoxaban group; Odds ratio 0.83 [95% CI, 0.38–1.83]; Log-rank P=0.65). All clinically relevant bleeding events occurred in 22 patients (14.6%) in 12-month edoxaban group and in 27 patients (15.8%) in 3-month edoxaban group (Odds ratio 1.40 [0.90–2.19]; Log rank P=0.13), resulting in the comparable risk of bleeding in the 12-month edoxaban group. Conclusions Our study suggests that 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT prevents recurrent VTE or VTE-related death without increasing the risk of bleeding compared to 3-month edoxaban treatment.primary endpointsecondary endpoint

The impact of body mass on cardiovascular outcomes in patients with acute coronary syndrome

Abstract Background Patients with acute coronary syndrome (ACS) and extreme body weights exhibit varying risks of bleeding and thrombotic outcomes. Furthermore, extreme body weights can influence the pharmacodynamic response to potent P2Y12 inhibitors (ticagrelor/prasugrel) and clopidogrel. Purpose This study aims to assess the impact of extreme body weights on cardiovascular outcomes, as well as the comparative efficacy and safety of potent P2Y12 inhibitors versus clopidogrel. Methods Data was extracted from the FORCE-ACS registry, a prospective, multicentre, registry, enrolling patients with ACS. Patients were stratified (in kg/m2) into the categories: underweight (body mass index [BMI] ≤20.0), normal weight (20.1–24.9), overweight (25.0–29.9), class 1 (30.0–34.9) and class 2 obesity (≥35.0). The primary thrombotic endpoint was major adverse cardiac events (MACE), a composite of cardiovascular death, myocardial infarction (MI), or stroke. The primary bleeding endpoint was defined as Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. Cox proportional hazard models and Kaplan-Meier survival curves were used to estimate the risk of clinical events across the BMI categories. Restricted cubic splines were made to assess the continuous association of BMI with the risk of the primary endpoints, stratified for P2Y12-inhibitor therapy (potent vs. clopidogrel) and gender. Results The total included population consisted of 5,864 patients with ACS (mean age 65.2 years, 72.4% men), and were stratified into underweight (N=112 [2%]), normal weight (N=1,627 [28%]), overweight (N=2,697 [46%]), class 1 obesity (N=1,081 [18%]) and class 2 obesity (N=347 [6%]). Compared with normal weight (10.8%), the rate of primary bleeding outcome was higher in underweight (15.2%) patients, but lower in the overweight (8.9%), class 1 obesity (7.9%) and class 2 obesity (6.3%) categories. MACE occurred in 9.8% for the underweight group, 7.9% for normal weight, 7.0% for overweight, 8.0% for class, and 6.1% for class 2 obesity. After adjusting for confounding factors such as age, gender, cardiovascular risk factors, access site, and medical therapy, each unit increase in BMI was associated with a decreased bleeding risk (hazard ratio [HR] 0.97, 95% CI 0.95-0.99, p = 0.02), with no significant association found for MACE. Similar findings are demonstrated in the Kaplan Meier analysis (Figure 1A-1B). Subgroup analysis regarding bleeding risk and BMI did not show a significant interaction for potent P2Y12-inhibitor therapy versus clopidogrel and gender (P-value for interaction: 0.04 and 0.32, respectively)(Figure 2A-2D). Conclusions Our findings indicate a stronger correlation between BMI and bleeding risk compared to thrombotic risk, showing an increased risk for bleeding in patients with a low BMI. These results underscore the importance of careful monitoring and tailored interventions to mitigate bleeding risk in underweight patients.

Thirty days clinical outcomes following stent implantation with aspirin-free prasugrel monotherapy in non-ST segment elevation myocardial infarction. Interim report from ASET-Japan pilot study

Abstract Background Dual antiplatelet therapy with a P2Y12 inhibitor, in addition to aspirin, is the standard therapy after percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) to prevent ischemic cardiovascular events. The Acetyl-Salicylic Elimination Trial (ASET) pilot studies conducted in Japan in patients with NSTE-ACS investigated the safety and feasibility of a low-dose prasugrel monotherapy after PCI. Purpose To ensure the safety of the patients, enrolment in the study was implemented only after confirmation of a successful procedure. The abstract reports our interim analysis, aimed at evaluating preliminary safety and feasibility. Methods The ASET-Japan pilot study was designed to explore the feasibility and safety of a low dose of prasugrel monotherapy (3.75mg/day), without adjunctive aspirin, after optimal PCI using Everolimus eluting stent (EES) in Japanese patients with non-ST-segment elevation acute coronary syndromes. The primary endpoint in the ASET-Japan NSTE-ACS (Phase 2) is a 12-month clinical outcome. The study is currently in the follow-up phase. All the target lesions were treated with a platinum-chromium everolimus-eluting stent. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 12-month. If more than 3 events occurred, trial enrollment would have to be terminated by the data and safety monitoring board. Results One hundred one patients were enrolled after successful index PCI and completed a 30 days follow-up. The mean age was 69.1±12.3 years and 75.2% was male. The mean anatomical SYNTAX score was 7.9±4.7. Unstable angina (UAP) and NSTEMI were seen in 24.8% (25/101) and 75.2% (75/101) patients, respectively. According to the Braunwald classification, 8 percent of the patients were categorised as Class IA UAP, 48% as Class IB, 20% as Class IIB, 4% as Class IIIA and 20% as Class IIIB. In NSTEMI patients, the median (IQR) pre-procedural troponin value (cardiac Troponin T or I) was 2.79 (1.12 – 22.27) times the Upper Limit of Normal. According to the PRECISE DAPT score, 36.6% of patients were categorised as High Bleeding Risk (HBR) with scores above 25. At one month, the primary ischemic endpoints of cardiac death, target-vessel spontaneous MI or definite Stent thrombosis did not occur. Two patients (2.0%) had BARC type 3a bleeding. Conclusion Prasugrel monotherapy in the first 30 days following platinum-chromium everolimus-eluting stent deployment is a feasible and safe strategy in NSTE-ACS patients with simple anatomy and successful PCI.

Real-world implementation of a genotype-guided p2y12-inhibitor de-escalation strategy in acute coronary syndrome patients

Abstract Background CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel, may optimize the balance between ischemic and bleeding risk in ACS patients. Purpose Compare bleeding and ischemic event rates in genotyped patients versus standard care. Methods Since 2015, ACS patients in the FORCE-ACS registry received standard dual antiplatelet therapy (DAPT). Since 2021, immediate genotype-guided P2Y12-inhibitor de-escalation was applied, switching non-carriers of the loss-of-function allele CYP2C19*3 or CYP2C19*2 from ticagrelor or prasugrel to clopidogrel, while loss-of-function carriers, carrying at least one loss-of-function allele, remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction (MI) or stroke and the primary bleeding endpoint, BARC 2, 3, or 5 bleeding, were compared between genotyped those on standard DAPT after one year. Results Among 5,321 enrolled ACS patients, 406 underwent genotyping, compared with 4,915 non-genotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were non-carriers, whereas 34.7% (n=141) were loss-of-function carriers. The primary ischemic endpoint occurred in 5.2% of patients in the genotyped cohort compared to 6.9% in the standard care cohort (adjHR 0.88, 95% CI 0.56–1.38). The rate of the primary bleeding endpoint was lower in the genotyped cohort compared to the standard care cohort (4.7% vs. 9.8%; adjHR 0.50, 95% CI 0.31-0.78). Conclusion These results demonstrate the feasibility of a CYP2C19 genotype-guided P2Y12-inhibitor de-escalation strategy in a real-world ACS population. This strategy reduced bleeding events, while ischemic events were not increased as compared to a standard DAPT regime.Primary ischemic endpointBARC 2, 3 or 5 bleeding

Post-PCI anticoagulation with unfractionated heparin in acute coronary syndrome: insight from the STOPDAPT-3 trial

Abstract Background The guidelines recommend the post-procedural anticoagulation should be discontinued after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) except for the specific indications.(1) However, these guideline recommendations were not well supported by data, and therefore, post-PCI parental anticoagulation has been commonly implemented in patients with ACS in the previous studies.(2-5) Purpose To clarify the preference and clinical situations of post-PCI unfractionated heparin (UFH) in ACS patients and to explore the influence of post-PCI UFH on cardiovascular and bleeding outcomes. Methods STOPDAPT-3 trial is a randomized controlled trial to demonstrate the efficacy and safety of the aspirin-free prasugrel monotherapy strategy compared to the conventional dual antiplatelet therapy after PCI in patients with high-bleeding risk or ACS.(6) Data on periprocedural heparin use and its doses were vigorously collected. The current study population was the ACS patients enrolled in the STOPDAPT-3 without use of mechanical circulatory support devices. The two co-primary endpoints were the bleeding outcome defined as the BARC 3 or 5 criteria and the cardiovascular outcome defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Outcomes were assessed at 30 days from index PCI. Results Among 4088 ACS study patients, 2339 (57.2%) patients received post-PCI UFH. Median dose of UFH was 7.1 (IQR 6.0-8.8) units/kg/hour and the median duration was 25 (IQR 24-48) hours. As many as 57.7% of patients received 10000 units/day of heparin after PCI irrespective of body weight. STEMI patients more frequently received post-PCI UFH compared to NSTE-ACS (72.3% and 38.8%, P&amp;lt;0.001) and the patients with intraprocedural adverse angiographic findings such as thrombus, slow-flow, no-reflow, or final TIMI flow &amp;lt;=2 also more frequently received post-PCI UFH than those without (67.6% and 47.5%, P&amp;lt;0.001). Post-PCI UFH was associated with a significantly increased risk of bleeding endpoint (4.75% and 2.52%, adjusted HR 1.69 [95%CI 1.15-2.46], P=0.007) and a numerically increased risk of cardiovascular endpoint (3.16% and 1.72%, adjusted HR 1.56 [95%CI 0.98-2.46], P=0.06). Even in the patients with intraprocedural adverse angiographic findings, post-PCI UFH did not show a clear benefit for cardiovascular endpoint (3.15% and 1.72%, adjusted HR 1.73 [95%CI 0.88-3.41]. P=0.11). Conclusion(s) Post-PCI anticoagulation with UFH was frequently implemented in ACS patients enrolled in the latest large Japanese clinical trial. Post-PCI UFH use was associated with harm in terms of bleeding without a benefit in reducing cardiovascular events.

Imaging characteristics and clinical outcomes of hemodialysis vs. non-hemodialysis patients undergoing transcatheter aortic valve replacement: a Japanese single-center experience.

In 2021, Japan approved transcatheter aortic valve replacement (TAVR) for end-stage renal disease patients on hemodialysis (ESRD-HD). Yet, clinical/anatomical differences and outcomes between patients with and without ESRD-HD remain underexplored. This single-center study enrolled consecutive patients who underwent TAVR with the SAPIEN 3 between 2021 and 2023. Baseline characteristics and outcomes up to 1year were compared. Inverse probability treatment weighting (IPTW) approach and Cox regression were used. Among 287 eligible patients, 59 had ESRD-HD. Patients with ESRD-HD were predominantly male (59.2% vs. 40.7%; p = 0.01), younger (78.0 [73.5-83.5] vs. 84.0 [79.8-88.0]; < 0.001), with lower body mass index (21.4 [19.6-23.3] vs. 22.9 [20.3-25.3]; p = 0.02], higher surgical risk (Society of Thoracic Surgeons Predicted Risk of Mortality ≧8%: 28 [47.5%] vs. 34 [14.9%]; p < 0.001), and more peripheral artery disease (25.4% vs. 4.8%; p < 0.001). Patients with ESRD-HD had a significantly higher prevalence of severely calcified femoral arteries (12.5% vs. 2.6%; p < 0.001). However, there were no differences in the computed-tomographic (CT) anatomical characteristics of the aortic valve complex (AVC), including the aortic valve calcium score (1995 [1372-3374] vs. 2195 [1380-3172]; p = 0.65) or the presence of moderate or severe left ventricular outflow tract calcification (4.3% vs. 5.2%; p > 0.99). Major vascular complications were rare, and technical (98.3% vs. 98.7%; p > 0.99) and device success (75.9% vs. 82.4%; p = 0.26) rates were high in both. At 1year, there were no significant differences in a composite endpoint of death, stroke, major bleeding, or myocardial infarction (32.4% vs. 33.2%; HR 1.12; 95% CI 0.45-2.80; p = 0.81), nor its components after baseline adjustment.

An aspirin-free strategy for percutaneous coronary intervention in patients with diabetes: a pre-specified subgroup analysis of the STOPDAPT-3 trial.

Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown. We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% versus 5.47%; HR, 0.92; 95%CI, 0.66-1.28 and non-diabetes: 3.99% versus 4.07%; HR, 0.98; 95%CI, 0.69-1.38; P for interaction=0.81) and cardiovascular (diabetes: 5.54% versus 5.15%; HR, 1.08; 95%CI, 0.78-1.49 and non-diabetes: 2.95% versus 2.47%; HR, 1.20; 95%CI, 0.79-1.82; P for interaction=0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes. The effects of an aspirin-free prasugrel monotherapy (3.75mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.

Incidence and clinical impact of inappropriate periprocedural and perioperative management of antiplatelet therapy

Background and aimsThere is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in “real life” in Spain. MethodsA prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. ResultsWe included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. ConclusionsDespite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the “real world” remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.

Randomized Trial of COBRA PzF Stenting to Reduce the Duration of Triple Therapy: The COBRA-REDUCE Trial.

Patients with an indication for oral anticoagulation who undergo percutaneous coronary intervention require a combination of oral anticoagulation and antiplatelet therapy. The use of a coronary stent with a thromboresistant and pro-healing coating may allow an abbreviated duration of dual antiplatelet therapy (DAPT) without an increase in the risk of thromboembolic events. Patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention were randomized to treatment with the COBRA polyzene F (PzF) stent followed by 14 days of DAPT or a Food and Drug Administration-approved new-generation drug-eluting stent followed by 3 or 6 months of DAPT. The bleeding coprimary end point was Bleeding Academic Research Consortium type ≥2 beyond 14 days (or after hospital discharge) until 6 months. The thromboembolic coprimary end point was the composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, or ischemic stroke at 6 months. The trial hypothesis was that the COBRA PzF stent strategy would be superior with respect to bleeding events and noninferior with respect to thromboembolic events. A total of 996 patients underwent randomization. The bleeding end point occurred in 37 of 475 patients (7.8%) in the COBRA PzF group and 47 of 482 patients (9.8%) in the control group (difference, -2.0 [95% CI, -5.6 to 1.6]; P=0.14). The thromboembolic end point occurred in 37 of 492 patients (7.5%) in the COBRA PzF group and 24 of 490 patients (4.9%) in the control group (difference, 2.6%; prespecified noninferiority margin 5%, upper limit of 1-sided 95% CI of the difference, 5.2%; Pnoninferiority=0.07). In patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention, treatment with the COBRA PzF stent plus 14 days of DAPT was not superior with respect to bleeding events and was not noninferior with respect to thromboembolic events at 6 months compared with treatment with standard Food and Drug Administration-approved drug-eluting stent plus 3 to 6 months of DAPT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02594501.

Comparison of clinical outcomes between ticagrelor and clopidogrel in patients with acute coronary syndrome and left ventricle dysfunction undergoing percutaneous coronary intervention: An observational study.

Patients with acute coronary syndrome (ACS) and left ventricular (LV) dysfunction undergoing percutaneous coronary intervention (PCI) need adequate antithrombotic protection. We aim to compare the clinical outcomes between ticagrelor and clopidogrel in these patients. In total, 336 patients with ACS and LV dysfunction who undergoing PCI were included in this retrospective observational study. Of these, 137 received clopidogrel and 199 received ticagrelor. There was a 6-month follow-up period during which clinical outcomes were monitored. The incidence of the composite endpoint (23.1% vs 13.9%, P = .041) and bleeding events (6.5% vs 1.5%, P = .027) in the ticagrelor group were significantly higher compared to the clopidogrel group. Multivariate logistic regression analysis revealed that age (P = .006), hypertension (P = .007), liver insufficiency (P = .022), previous MI (P = .014) and ticagrelor (P = .044) were independent risk factors that affect the efficacy outcome. Age (P = .027) and ticagrelor (P = .016) were the independent risk factors for the safety outcome. Furthermore, in Cox survival regression analysis model, the survival rate of the efficacy endpoint in the clopidogrel group was seemingly higher than in the ticagrelor group (HR = 1.68, 95% CI: 0.97-2.90, P = .065). The survival rate of the bleeding endpoint in the clopidogrel group was higher than in the ticagrelor group (HR = 2.00, 95% CI: 1.17-3.40, P = .011). Compared to clopidogrel, ticagrelor showed increased risk of efficacy outcome and major bleeding events during 6-month follow-up in patients with ACS and LV dysfunction undergoing PCI.

Efficacy and safety of bemiparin as treatment of venous thromboembolic disease in the elderly.

As the elderly population continues to grow worldwide, it becomes crucial to explore safe and effective treatment options to manage venous thromboembolic disease in this vulnerable demographic group. We carried out a retrospective cohort study (January 2017-December2021) to analyse the efficacy and safety of bemiparin as a treatment for venous thromboembolic disease in 223 patients. We compared patients aged ≥65 years (elderly; n = 153) with patients aged less than 65 years (adults; n = 70) for a combined end point of death, recurrent thromboembolism, and major bleeding at 30 days. Elderly (mean age 79 ± 7.7 years) and adult patients (mean age 51.5 ± 11.6 years) received similar bemiparin doses 8470 ± 2362 International units (IU)/d versus 8754 ± 1593 IU/d, during a similar median [Interquartile range] period of 28 [9-118] versus 30 [10-90] days, respectively. At 30-day follow up a total of 24 elderly patients (15.7%), reached at least one of the end points, as compared with six adult patients (8.6%) (absolute difference 7.1%; 95% confidence interval [95%CI], -1.6 to 15.8). Recurrence of venous thromboembolic disease occurred in five elderly patients (3.3%) and in five adult patients (7.1%) (absolute difference -3.9%; 95%CI, -10.5 to 2.8).There were two episodes of major bleeding each in elderly (1.3%) and adult (2.9%) patients (absolute difference -1.6%; 95% CI, -5.8 to 2.7). Bemiparin showed a similar efficacy and safety profile in the treatment of venous thromboembolic disease in elderly and adult patients.

Real-World Implementation of a Genotype-Guided P2Y12 Inhibitor De-Escalation Strategy in Acute Coronary Syndrome Patients.

CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1year. Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were noncarriers, 88.7% (n=235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n=21) of patients in the genotyped cohort compared to 6.9% (n=337) in the standard care cohort (adjusted HR: 0.82; 95%CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95%CI: 0.30-0.76). The implementation of a CYP2C19 genotype-guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.

Aspirin versus Clopidogrel Monotherapy After Percutaneous Coronary Intervention: 1-Year Follow-up of the STOPDAPT-3 Trial.

There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). In the STOPDAPT-3, patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomly assigned to either 1-month DAPT with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke, and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5. Of 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, ACS 74.6%, and HBR 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint (4.5 and 4.5 per 100 person-year, hazard ratio [HR] 1.00 [95% confidence interval (CI) 0.77-1.30], P = .97), and bleeding endpoint (2.0 and 1.9, HR 1.02 [95% CI 0.69-1.52], P = .92). Aspirin monotherapy compared to clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after PCI with DES.

Aspirin-Free Strategy for Percutaneous Coronary Intervention in Patients With Oral Anticoagulation: Prespecified Subgroup Analysis From the STOPDAPT-3 Trial.

The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated. We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46). The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Aspirin-free P2Y12 inhibitor monotherapy immediately after percutaneous coronary intervention: A systematic review

BackgroundA modified antiplatelet therapy approach after percutaneous coronary intervention (PCI), specifically reducing dual antiplatelet therapy (DAPT) duration and transitioning to P2Y12 inhibitor monotherapy, may offer advantages in terms of bleeding risk reduction. However, the impact of initiating aspirin-free P2Y12 inhibitor monotherapy immediately after PCI is not yet fully understood. MethodsWe systematically searched the PubMed and Embase databases until January 2024 for studies that examined the use of P2Y12 inhibitor monotherapy as a treatment approach without initial DAPT following PCI. ResultsFour single-arm pilot prospective studies and 1 randomized controlled trial were included. In acute coronary syndrome patients with P2Y12 monotherapy following aspirin withdrawal immediately after PCI, the occurrence rates of the primary ischemic and bleeding endpoint were 2.91 % (8 out of 275 patients) and 1.09 % (3 out of 275 patients) respectively, whereas both the incidence rates of the primary ischemic and bleeding endpoints were 0.25 % (1 out of 407 patients) in individuals with stable coronary artery disease. In the STOPDAPT-3 trial comparing the effect of aspirin-free prasugrel monotherapy with standard DAPT after PCI, no differences were found in the primary ischemic or bleeding endpoints and most secondary outcomes (death, stroke, and myocardial infarction). However, there was an increased risk of coronary revascularization and stent thrombosis in the no-aspirin group. ConclusionsSingle-arm studies suggest the safety and feasibility of aspirin-free P2Y12 inhibitor monotherapy without initial DAPT after PCI in selected patients with acute coronary syndrome or stable coronary artery disease. However, the safety and efficacy of this aspirin-free approach compared with standard DAPT strategies following PCI still require further investigation.

Coronary artery disease and heart failure: Late-breaking trials presented at American Heart Association scientific session 2023.

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure (HF). The dapagliflozin in patient with acute myocardial infarction (DAPA-MI) trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo, with no difference in cardiovascular outcomes. The MINT trial showed that in patients with acute MI and anemia (Hgb < 10 g/dL), a liberal transfusion goal (Hgb ≥ 10 g/dL) was not superior to a restrictive strategy (Hgb 7-8 g/dL) with respect to 30-day all-cause death and recurrent MI. The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy, percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure. The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist, placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year. The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given ≥ 6 months after cardiac transplantation. Providing patients being treated for HF with reduced ejection fraction (HFrEF) with specific out-of-pocket (OOP) costs for multiple medication options at the time of the clinical encounter may reduce 'contingency planning' and increase the extent to which patients are taking the medications decided upon. The primary outcome, which was cost-informed decision-making, defined as the clinician or patient mentioning costs of HFrEF medication, occurred in 49% of encounters with the checklist only control group compared with 68% of encounters in the OOP cost group.