Risk Of Ischemic Events Research Articles

Ischemic and Bleeding Outcomes in Patients Who Underwent Percutaneous Coronary Intervention With Chronic Kidney Disease or Dialysis (from a Japanese Nationwide Registry)

The relation between chronic kidney disease (CKD) and outcomes in patients receiving percutaneous coronary intervention (PCI) is thought to be bidirectional; these patients are at a higher risk of ischemic and bleeding events. From a Japanese nationwide PCI registry, ischemic (cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke) and bleeding events (fatal or nonfatal major bleeding) 1 year after discharge among patients who had second- or newer-generation drug-eluting stent implantation were analyzed. Patients on oral anticoagulants were excluded. Patients were stratified according to their preprocedural renal function: CKD stages 1 to 2 (estimated glomerular filtration rate [eGFR] ≥60ml/min/1.73m2), 3 (eGFR 30 to 59), or 4 to 5 (eGFR <30), or those receiving dialysis. Overall, 23,349 patients, including 2,798 patients with CKD 3 to 5 (12.0%) and 1,464 patients on dialysis (6.3%), were investigated. One-year ischemic events were observed in 1.5%, 5.2%, 9.7%, and 5.3% in the CKD stages 1-to-2, 3, 4-to-5, and dialysis groups, respectively; patients with CKD stages 3 or 4 to 5 and those receiving dialysis were associated with higher risks of ischemic events after adjustment of covariates than were patients without CKD. Compared with ischemic events, 1-year bleeding events were low, with incidence rates of 1.5%, 2.0%, 3.4%, and 2.3%, respectively. Furthermore, the presence of CKD or dialysis was not associated with a higher risk of bleeding events after adjustment of covariates. In conclusion, in the contemporary nationwide PCI registry, the presence of CKD and dialysis was independently associated with a higher risk of ischemic events but not with bleeding events, and this suggests a need to alter the models of care delivery in these patients.

Stroke and Myocardial Infarction in Patients with Abdominal Aortic Aneurysm and New-Onset Atrial Fibrillation.

We investigated the association between new-onset atrial fibrillation (AF) and risk of stroke and myocardial infarction (MI) in patients with abdominal aortic aneurysmal (AAA) disease. Observational crossover study using Danish nationwide data, including patients with AAA and incident AF between 1997 and 2018. We estimated the 1-year risk of stroke and MI and the within-individual odds ratios (ORs) of ischemic events before and after an AF diagnosis, stratified by year of AF diagnosis (1997-2010 and 2011-2018), and supplemented with analyses on changes in use of antithrombotic therapy. A total of 3,035 AAA patients were included: 1,040 diagnosed during 1997 to 2010, and 1,995 during 2011 to 2018 (22.2% females, median age 78 years; median CHA2DS2-VASc score 4; interquartile range: 3-5). One-year risk of ischemic events after AF was 5.9% (confidence interval [CI] 95%: 4.6-7.5%) and 4.5% (CI 95%: 3.7-5.5%) for stroke and 5.4% (CI 95%: 4.2-6.9%) and 4.0% (CI 95%: 3.2-4.9%) for MI during 1997 to 2010 and 2011 to 2018, respectively. The OR of ischemic stroke before and after incident AF was 2.8 (CI 95%: 1.6-5.2) during 1997 to 2010; and 2.4 (CI 95%: 1.5 to 3.9) during 2011 to 2018, and 3.5 (CI 95%: 1.7-7.5) and 1.5 (CI 95%: 0.9-2.4) for MI. One-year proportion of prescription claims for oral anticoagulants after AF changed from 66.1% in 1997 to 2010 to 82.6% in 2011 to 2018, while antiplatelet prescription claims changed from 80.8 to 60.9%. Cardiovascular prognosis has improved in patients with prevalent AAA disease and new-onset AF in concordance with optimization of antithrombotic therapy over time. A diagnosis of AF conferred residual risk of stroke and MI.

Safety and Efficacy of Tirofiban Bridging Therapy During a Hybrid Carotid Artery Stenting and Off-pump Coronary Artery Bypass Grafting Surgery: A Single-center Study

The optimal perioperative antithrombosis management for carotid artery stenting (CAS) and coronary artery bypass grafting (CABG) hybrid surgeries remains unclear; however, a more aggressive antithrombotic therapy might be required after a hybrid CAS+CABG duo stent-related intimal injury or the use of protamine-neutralizing heparin. This study evaluated the safety and efficacy of tirofiban as a bridging therapy after a hybrid CAS+CABG surgery. Between June 2018 and February 2022, a total of 45 patients undergoing a hybrid CAS+off-pump CABG surgery were divided into either the control group (standard dual antiplatelet therapy postsurgery, n=27) or the tirofiban group (tirofiban bridging+dual antiplatelet therapy, n=18). The 30-day outcome was compared between the 2 groups, and the primary end points included stroke, postoperative myocardial infarction, and death. Two patients (7.41%) from the control group experienced a stroke. There was a trend toward a lower rate of composite end points, including stroke, postoperative myocardial infarction, and death, within the tirofiban group that did not reach statistical significance (0% vs 11.1%; P=0.264). The need for a transfusion was similar between the 2 groups (33.33% vs 29.63%; P=0.793). There were no major bleeding events in the 2 groups. Tirofiban bridging therapy was safe, with a trend toward reducing the risk of ischemic events after a hybrid CAS+off-pump CABG surgery. Tirofiban might be a feasible periprocedural bridging protocol in high-risk patients.

Abstract 3: Cerebral Small Vessel Disease Burden For Bleeding Risk During Antithrombotic Therapy -BAT2-

Background: Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs. Purpose: To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden. Methods: Patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were prospectively enrolled from 52 hospitals across Japan between 2016 and 2019. Multimodal brain MRI was acquired at baseline for all patients under prespecified conditions. All MRI examinations were interpreted by a central diagnostic radiology committee for cerebral microbleeds, lacunes, white matter hyperintensities, and enlarged basal ganglia perivascular spaces, for calculation of a total SVD score (range 0-4). The primary outcome was major bleeding during 2-year follow-up. Secondary outcomes included bleeding in each site and ischemic events. Event risks according to SVD score were estimated with multivariable Cox proportional hazards models. Results: Of the analyzed 5250 patients (1736 women; median age, 73 years; 9933 patient-years follow-up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median of the total SVD score was 2 (IQR 1-3). As SVD score increased, advanced age, hypertension, anemia, and chronic kidney disease were more prevalent (P&lt;0.001 for each). A unit increase of SVD score was associated with a higher risk of major bleeding (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.29-1.85) and intracranial hemorrhage (adjusted HR 1.61, 95% CI 1.28-2.03). With SVD score 4 compared to score 0, extracranial major bleeding (adjusted HR 3.37, 95% CI 1.12-10.15) and gastrointestinal bleeding (adjusted HR 2.54, 95% CI 1.02-6.35) were also significantly increased. A higher SVD score was associated with a mild but significant elevation of ischemic event risk (adjusted HR per unit increase 1.17, 95% CI 1.06-1.29). Conclusions: The total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting a broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy.

Dual Antiplatelet Therapy Does Not Increase Bleeding Risk in Percutaneous Gastrostomy Tube Placement: Network Meta-Analysis.

Gastrostomy tube (G tube) is a commonly performed procedure for nutritional support. Current guidelines recommend discontinuation of dual antiplatelet therapy (DAPT) prior to G tube placement to reduce bleeding risk. We aim to compare bleeding risk in single, dual and no antiplatelet therapy during G tube placement. We searched PubMed, Embase, Cochrane, and Web of Sciences to include comparative studies evaluating single antiplatelet (aspirin, clopidogrel), dual antiplatelet (DAPT, aspirin and clopidogrel), and no antiplatelet therapy. Direct as well as network meta-analyses comparing these arms were performed. Risk Differences (RD) with confidence intervals were calculated. 12 studies with 8471 patients were included. On direct meta-analysis, there was no significant difference noted between DAPT compared to Aspirin (RD 0.001 95% CI - 0.012 to 0.014, p = 0.87), Clopidogrel (RD 0.001 95% CI - 0.009 to 0.010, p = 0.92) or no antiplatelet group (RD 0.007 95% CI - 0.011 to 0.026, p = 0.44). Results were consistent on network meta-analysis and no difference was noted in bleeding rates when comparing DAPT with Aspirin (RD 0.001, 95% CI - 0.007 to 0.01, p = 0.76), Clopidogrel (RD 0.001, 95% CI - 0.01 to 0.011, p = 0.90) and no antiplatelet group (RD 0.002, 95% CI - 0.007 to 0.012, p = 0.62). There is no significant difference in bleeding risk between DAPT, single antiplatelet or no antiplatelet therapy on a population level. On an individual level, risk of ischemic events should be weighed against the risk of bleeding based on patient circumstances and risk profile. Our findings offer to provide additional data to make an informed decision between patients and physicians to make clinical decisions by assessing individual risks and benefits for optimal care of complex patients.

Influence of body weight and body mass index on the chronic pharmacokinetic and pharmacodynamic responses to clinically available doses of ticagrelor in patients with chronic coronary syndromes

Ticagrelor has multiple indications, including for some patients with chronic coronary syndromes (CCS) at high risk of ischaemic events. Body mass can potentially affect pharmacodynamics (PD) and pharmacokinetics (PK). We investigated the influence of body mass (range 53–172 kg, 20.8–46.9 kg/m2) on PD/PK in 221 CCS patients receiving ticagrelor 60 mg or 90 mg twice-daily (BD) during two randomised-controlled trials. Correlations between body weight (BW) or body mass index (BMI) and PD/PK measurements obtained during maintenance treatment at trough (‘pre-dose’) and peak effect (‘post-dose’) were assessed. BW and BMI correlated with P2Y12 reactivity units at pre-dose (e.g. BW:R = 0.26, p = 0.008) but not post-dose timepoints. BW affected ticagrelor active metabolite (TAM) levels (e.g. 60 mg BD, post-dose:R = -0.39, p < 0.0001) and there was evidence of an inverse power law relationship between BW and TAM-to-ticagrelor ratio. PK with ticagrelor 60 mg correlated significantly with BMI. BW and BMI did not affect the chance of high platelet reactivity, which remained very low across the whole cohort. There was no difference in PRU between the two doses of ticagrelor within each weight or BMI group. Body mass has modest effects on the PK/PD response to ticagrelor in patients with CCS but currently-used regimens appear adequate across the range of BW/BMI studied.

Antiphospholipid Autoantibodies and Brain Ischemic Lesions in Infective Endocarditis.

Stroke is a frequent and severe complication of infective endocarditis (IE).[1] [2] Although different factors associated with a high risk of embolic complications are known,[3] no biomarker has been identified yet. Various autoantibodies have been described in the course of IE, including antiphospholipid (aPL) autoantibodies.[4] [5] [6] Their detection at IE diagnosis may be of particular interest considering the risk of ischemic events. We aimed to determine the frequency of anticardiolipin (aCL), anti-β2GPI (aβ2GPI), antiphosphatidylethanolamine (aPE), and antiphosphatidyl/prothrombin (aPS/PT) autoantibodies in patients with IE and their association with brain ischemic events detected by systematic brain magnetic resonance imaging (MRI).

Thoracic aortic aneurysm and atrial fibrillation: clinical associations with the risk of stroke from a global federated health network analysis

BackgroundAn association with aortic aneurysm has been reported among patients with atrial fibrillation (AF). The aims of this study were to investigate the prevalence of thoracic aorta aneurysm (TAA) among patients with AF and to assess whether the co-presence of TAA is associated with a higher risk of adverse clinical outcomes.Methods and resultsUsing TriNetX, a global federated health research network of anonymised electronic medical records, all adult patients with AF, were categorised into two groups based on the presence of AF and TAA or AF alone. Between 1 January 2017 and 1 January 2019, 874,212 people aged ≥ 18 years with AF were identified. Of these 17,806 (2.04%) had a TAA. After propensity score matching (PSM), 17,805 patients were included in each of the two cohorts. During the 3 years of follow-up, 3079 (17.3%) AF patients with TAA and 2772 (15.6%) patients with AF alone, developed an ischemic stroke or transient ischemic attack (TIA). The risk of ischemic stroke/TIA was significantly higher in patients with AF and TAA (HR 1.09, 95% CI 1.04–1.15; log-rank p value < 0.001)The risk of major bleeding was higher in patients with AF and TAA (OR 1.07, 95% CI 1.01–1.14), but not significant in time-dependent analysis (HR 1.04, 95% CI 0.98–1.10; log-rank p value = 0.187),ConclusionThis retrospective analysis reports a clinical concomitance of the two medical conditions, and shows in a PSM analysis an increased risk of ischemic events in patients affected by TAA and AF compared to AF alone.

Real-World Data on the Incidence of Stroke, Myocardial Infarction, and Mortality Among Nonvalvular Atrial Fibrillation Patients in Türkiye: New Oral Anticoagulants-TURKey Study.

Atrial fibrillation (AF) is strongly associated with an increased risk of ischemic events. Anticoagulation focuses on reducing the risk of embolism. Guideline recommended CHA2DS2-VASc scoring system is most widely used; however, different scoring systems do exist. Thus, we sought to assess the impact of anticoagulant treatment and different scoring systems on the development of stroke, myocardial infarction, and all-cause mortality in patients with nonvalvular AF. The present study was designed as a prospective cohort study. The enrollment of the patients was conducted between August 1, 2015, and January 1, 2016. The follow-up period was defined as the time from enrollment to the end of April 1, 2017, which also provided at least 12 months of prospective follow-up for each patient. A total of 1807 patients with AF were enrolled. During the follow-up, 2.7% (48) of patients had stroke, 0.8% (14) had myocardial infarction, and 7.5% (136) died. The anticoagulation and risk factors in AF (ATRIA) score had a better accuracy for the prediction of stroke compared to other scoring systems (0.729, 95% CI, 0.708-0.750, P <.05). Patients under low-dose rivaroxaban treatment had significantly worse survival (logrank P <.001). Age, CHA2DS2-VASc score, R2CHADS2 score, ATRIA score, chronic heart failure, prior stroke, and being under low-dose rivaroxaban treatment were independent predictors of clinical endpoint (P <.001). Low-dose rivaroxaban treatment was independently and strongly associated with the combined clinical endpoint. Furthermore, the ATRIA score proved to be a stronger predictor of stroke in the Turkish population.

Rupture infected pseudoaneurysm on brachiocephalic AV-fistula: emergency and definitive management

Background: Vascular access bleeding is a rare event that can be fatal in hemodialysis patients. It requires emergency and surgical management to reduce the risk of ischemic events in the patient’s forearm and reduce mortality risk. Objective: To describe the clinical presentation, emergency and surgical intervention, and outcome of rupture-infected anastomotic pseudo aneurysm of the brachiocephalic arteriovenous fistula that underwent a definitive surgical procedure. Case Description: A 55-year-old man presented with bleeding on the AV-fistula surgery site, accompanied with pain and swelling on his forearm that occurred 3 hours before admission to the hospital. The Patient had a history of brachiocephalic AV-fistula surgery 3 weeks earlier. On physical examination, It was found that the surgical site wound looked wet and swollen, with lots of necrotic tissue and pus and lost stitches. In Emergency Departments, the patient was administered intravenous normal saline fluids, bleeding inhibitors and pressure bandages to reduce ongoing bleeding. Then the patient had planned for immediate vascular reconstruction surgery. The brachial artery is repaired using great saphenous vein patch plasty. Results: The patient’s postoperative 30-days follow-up went well, and there was no sign of complication, such as pain, infection, paresthesia, bleeding at the surgical site or ischemia in the distal forearm. Conclusion: Vascular access bleeding can be fatal to hemodialysis patients. Optimal treatment for the patient's life and hemodialysis access is a top priority. A good assessment of the condition of AVF and the choice of subsequent therapy greatly affect the patient's prognosis.

761 PRASUGREL OR CLOPIDOGREL IN PATIENTS WITH ACUTE CORONARY SYNDROMES AT DIFFERENT THROMBOTIC RISK: RESULTS FROM THE PROMETHEUS STUDY

Abstract Background Potent P2Y12 inhibitors are recommended in patients with acute coronary syndrome (ACS), although the optimal antithrombotic strategy should be tailored based on patients thrombotic and hemorrhagic risk profile. We evaluated if the benefits associated with prasugrel vs. clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) are similar in patients with different thrombotic risk profiles. Methods PROMETHEUS was a multicenter observational study comparing prasugrel vs. clopidogrel in ACS patients undergoing PCI. Patients were defined at high thrombotic risk if presenting with a clinical and a procedural risk feature. The primary endpoint was major adverse cardiac events (MACE), composite of death, myocardial infarction, stroke, or unplanned revascularization. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated using propensity-stratified analysis and with multivariable Cox regression. Results Among 16,065 patients, 4,293 were defined at high and 11,772 at low-to-moderate thrombotic risk. Patients receiving prasugrel had less comorbidities and risk factors than those treated with clopidogrel, both in the high and low-to-moderate thrombotic risk strata. High thrombotic risk patients had increased rates of ischemic and bleeding events at 90-day and 1-year follow-up. Patients treated with prasugrel had a lower adjusted 1-year risk of MACE (HR 0.86, 95% CI 0.77-0.96), irrespective of their thrombotic risk (pinteraction =0.32). Stratifying the study population by number of risk factors there was a significant interaction (pinteraction =0.026) for a greater reduction in MACE with prasugrel among patients with ≤1 thrombotic risk factor. The risk of clinically significant bleeding was similar in patients treated with prasugrel and clopidogrel. Conclusions Patients with ACS at high thrombotic risk who undergo PCI are at increased risk of adverse events at 1 year. Prasugrel, mainly reserved to patients with less comorbidities, reduced the risk of ischemic events both in patients at high and low-to-moderate thrombotic risk as compared with clopidogrel.

746 DAL COMPASS AI DATI DI REAL LIFE: UNO STUDIO CASO-CONTROLLO

Abstract Background The COMPASS trial showed that rivaroxaban plus aspirin was associated with fewer adverse cardiovascular events, but more major bleeding events, as compared with aspirin alone in patients with chronic vascular disease. The clinical benefit was particularly favorable in high-risk subgroups, who are frequently undertreated because of the fear of severe bleeding events. Purpose Our aim is to evaluate objective effects of anticoagulation strategies with rivaroxaban among patients with stable cardiovascular disease. Methods We considered a population of patients with stable cardiovascular disease (coronary and/or peripheral artery disease) which has had dual antiplatelet therapy (DAPT) for 1 year. Between them we selected 65 patients (52 males and 13 females, mean age 59±7 years) with high risk of ischemic events and low bleeding risk. We used DAPT Score and HAS BLED Score to enroll patients. We stopped them DAPT and starting a dual therapy combining rivaroxaban 2,5 mg twice daily plus aspirin 100 mg. We excluded patients with high bleeding risk and heart failure with less than 35% ejection fraction. At baseline they underwent blood tests, transthoracic echocardiography, six minutes walking test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ) Score, evaluation of carotid– femoral pulse wave velocity (cf-PWV) and ankle brachial index (ABI). We established 3, 6 and 12 months follow-up. Results At 3 months follow-up we evaluated 41 patients (the study is going on) repeating those exams and comparing them with the baseline ones. We observed that 35% of population had reduction of cf-PWV values and in 40% of population ABI increased. 15% of patients had also improvement of more than 100 meters in 6MWT. Particularly, reduction of cf-PWV and improvement of ABI values suggest that rivaroxaban 2,5 mg twice daily may have effects on vascular protection and arterial stiffness through different mechanisms such as improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties and platelet-dependent thrombin generation. Nevertheless none of the patients experienced subjective clinical improvement and the KCCQ Score was unmodified. This element indicates that patients at 3 months follow-up have imperceptible changes that can be documented only by diagnostic imaging evaluation and not by anamnestic data. Finally, an important evidence was that none of the patients at 3 months follow-up reported major bleeding events. Conclusion Preliminary data suggest that the addiction of rivaroxaban 2,5 mg to aspirin exerts vascular protection and its effects can be primarly documented by evaluation of cf-PWV and ABI. The 6MWT seems to play a minor role at 3 months assessment. The KCCQ may not be useful to fill in at 3 months follow-up because patients seem not to perceive subjective clinical improvement in this phase. If confirmed on a large cohort these results may give rivaroxaban a higher relevance not only for the power but also for the immediacy of its effects. Anyway, we are continuing our check to give our data more statistical significance and to test any role of the other parameters at 6 and 12 months follow-up.

No Antithrombotic Therapy After Transcatheter Aortic Valve Replacement: Insight From the OCEAN-TAVI Registry

BackgroundSeveral trials demonstrated that aspirin monotherapy compared with aspirin plus clopidogrel is associated with a lower incidence of bleeding without an increased risk of ischemic events in patients after transcatheter aortic valve replacement (TAVR); however, there remains a paucity of data to prove the necessity of even aspirin monotherapy. ObjectivesThis study aimed to compare clinical outcomes and valve performance of the 3 different antithrombotic strategies post-TAVR from the OCEAN-TAVI (Optimized transCathEter vAlvular iNtervention) registry. MethodsPatients who received anticoagulation or had procedural complications were excluded. The remaining patients were classified into 3 groups according to the antithrombotic regimen at discharge: 1) nonantithrombotic therapy (None); 2) single-antiplatelet therapy (SAPT); and 3) dual-antiplatelet therapy (DAPT). The primary outcome was the incidence of net adverse clinical events (NACEs) (ie, cardiovascular death, stroke, myocardial infarction, and life-threatening or major bleeding). ResultsOverall, 3,575 TAVR patients were included (None, 293; SAPT, 1,354; DAPT, 1,928). The median follow-up period was 841 days (IQR: 597-1,340 days). The incidence of NACEs did not differ between the groups (None vs SAPT: adjusted HR [aHR]: 1.18; P = 0.45; None vs DAPT: aHR: 1.09; P = 0.67). There was a lower incidence of all bleeding in patients with no antithrombotics (None vs SAPT: aHR: 0.63; P = 0.12; None vs DAPT: aHR: 0.51; P = 0.04). The valve performance was similar among the groups. Leaflet thrombosis was detected in 8.5% of the nonantithrombotic group. ConclusionsCompared with SAPT/DAPT, the nonantithrombotic strategy was not associated with an increased risk of NACEs and potentially reduced the risk of bleeding events. The nonantithrombotic strategy may be an acceptable alternative to SAPT/DAPT in selected patients with TAVR.

Prior Myocardial Infarction and Treatment Effect of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndromes - A Post-hoc Analysis of the ISAR-REACT 5 Trial.

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1-year all-cause death, MI, or stroke; the secondary safety end point was the composite of 1-year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38-2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71-1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03-2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99-1.65) in patients without prior MI (Pint=0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56-2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82-1.55) in patients without prior MI (Pint=0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

DAPT Regimens for Elderly and Patients with Respiratory Conditions a Scoping Review

Background: Although ticagrelor is more potent than clopidogrel, it is associated with higher risk of bleeding and dyspnea. Since elderly patients are at higher risk of bleeding there is a concern of whether they should be prescribed clopidogrel instead of ticagrelor and a shorter duration of DAPT or even a monotherapy antiplatelet. Additionally, guidelines recommend being cautious when prescribing ticagrelor to COPD and asthmatic patients, yet, it is unclear whether patients with respiratory conditions are at higher risk of dyspnea from ticagrelor. This scooping review is conducted to assess the safety and efficacy of ticagrelor versus clopidogrel in elderly ≥75 years and patients with respiratory conditions. Also, to investigate the most suitable antiplatelet duration for elderly patients ≥75 years. Method: EMBASE, MEDLINE, and Cochran library were systemically searched. Studies were included if they were published in English; included adult patients diagnosed with ACS; are ≥75 years old or diagnosed with respiratory disease (asthma, COPD); treated with DAPT including clopidogrel or ticagrelor or monotherapy antiplatelet; reported quantitative data regarding bleeding or dyspnea. Studies were excluded if they were published prior to 2006. Outcome of interest were cardiovascular events, bleeding, and dyspnea. Results: 13 articles met the inclusion criteria and were included: 5 RCTs, 1 non-RCT, and 7 subgroup analyses. Two studies compared the safety and efficacy of ticagrelor versus clopidogrel in COPD patients (one of the studies included asthmatic patients), 3 studies compared safety and efficacy of ticagrelor versus clopidogrel in elderly, and 8 studies compared the duration of DAPT in elderly. Conclusions: Available data suggests that COPD and asthmatic patients are not at higher risk of dyspnea from ticagrelor and might benefit more from ticagrelor since they are at higher risk of ischemic events, yet, it is associated with higher discontinuation rate. Additionally, there was no difference between clopidogrel and ticagrelor in elderly patients in regard to cardiovascular endpoint while clopidogrel might lower the risk of bleeding. Shorter duration of DAPT might also minimize the risk of bleeding in elderly. However, data regarding DAPT in elderly and respiratory disease patients is limited, and evidence regarding the most appropriate regimen remains inconclusive.

ANMCO Position paper: Evidence and practical indications for the use of low-dose rivaroxaban in stable coronary artery disease and peripheral artery disease

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

Early-start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage and high risk of ischemic events (E-start): Protocol for a multi-centered, prospective, open-label, blinded endpoint randomized controlled trial.

For severe spontaneous intracerebral hemorrhage (sSICH) patients with high risk of ischemic events, the incidence of postoperative major cardiovascular/cerebrovascular and peripheral vascular events (MACCPE) is notable. Although antiplatelet therapy is a potential way to benefit these patients, the severe hemorrhagic complications, e.g., intracranial re-hemorrhage, is a barrier for early starting antiplatelet therapy. This randomized controlled trial aims to identify the benefit and safety of early starting antiplatelet therapy after operation for sSICH patients with high risk of ischemic events. This study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial. We will enroll 250 sSICH patients with a high risk of ischemic events (including cerebral infarcts, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep venous thrombosis). The participants will be randomized in a 1:1 manner to early-start group (start antiplatelet therapy at 3 days after operation) and normal-start group (start antiplatelet therapy at 30 days after operation). The early-start group will receive aspirin 100 mg daily. The control group will not receive antithrombotic therapy until 30 days after operation. The efficacy endpoint is the incidence of MACCPE, and the safety endpoint is the incidence of intracranial re-hemorrhage. The Early-Start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage trial (E-start) is the first randomized trial about early start antiplatelet therapy for operated sSICH patients with a high risk of ischemic events. This study will provide a new strategy and evidence for postoperative management in the future. ClinicalTrials.gov, identifier NCT04820972; Available at: https://clinicaltrials.gov/ct2/show/NCT04820972?term=NCT04820972&draw=2&rank=1.Chinese Clinical Trial Registry, identifier ChiCTR2100044560; Available at: http://www.chictr.org.cn/showproj.aspx?proj=123277.

New opportunities of antithrombotic therapy in patients with type 2 diabetes mellitus and stable coronary heart disease for reducing the cardiovascular risk and cardiovascular complications: THEMIS, THEMIS-PCI trials

Patients with diabetes mellitus (DM) and coronary heart disease belong to a group with a very high risk of developing cardiovascular disease. In patients with coronary atherosclerosis, DM increases the risk of ischemic events by 2-4 times. Apparently, increased antithrombotic therapy has an advantage in patients with DM who have had myocardial infarction. However, until recently it was not clear there is such an advantage in patients with DM and stable coronary artery disease without prior myocardial infarction. The addition of ticagrelol to monotherapy of acetylsalicylic acid reduces the risk of major cardiovascular events in patients with type 2 DM and stable coronary artery disease undergoing percutaneous coronary intervention, if patients have a high risk of ischemic events.

Escalation and De-Escalation of Antiplatelet Therapy after Acute Coronary Syndrome or PCI: Available Evidence and Implications for Practice.

Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient's risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI.

Bleeding after percutaneous coronary intervention and selection of candidates for long-term dual antithrombotic treatment

Abstract Background The European Society of Cardiology recommends addition of a second antithrombotic drug (a P2Y12 inhibitor or rivaroxaban 2.5 mg twice daily) on top of aspirin in selected patients with chronic coronary syndrome (CCS) at high residual risk of ischemic events. However, this treatment increases bleeding risk, and identifying subsets of patients with the most favorable trade-off between ischemic and bleeding risk thus is essential. We hypothesized that patients undergoing percutaneous coronary intervention (PCI) who tolerate subsequent dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) without any bleeding complications selected themselves as candidates for prolonged dual antithrombotic therapy. Methods and results We included 30,531 patients with CCS treated with dual antiplatelet therapy after first-time PCI with a drug-eluting stent in Western Denmark (3.5 million inhabitants) from 1999 to 2018. Of these, 1,220 (4%) were hospitalized for bleeding within one year after PCI (bleeders) and 29,311 (96%) were not (non-bleeders). Patients were followed for maximum nine years (median follow-up 5.4 years). Bleeders had an increased nine-year risk of death (adjusted hazard ratio [aHR] 1.54, 95% CI 1.37–1.73) and hospitalization for bleeding (aHR 2.53, 95% CI 2.20–2.90). These associations were particularly strong for women. Looking at types of bleeding, the strongest predictors of death were gastrointestinal bleeding, cerebral bleeding, and anemia due to bleeding. Risks of myocardial infarction and ischemic stroke did not differ between bleeders and non-bleeders (Table). We then stratified non-bleeders according to their thromboembolic risk using the CHADS-P2A2RC score – a validated clinical risk prediction model developed to estimate thromboembolic risk in patients without atrial fibrillation. Non-bleeders with a high estimated thromboembolic risk (CHADS-P2A2RC score ≥4) had higher nine-year risks of myocardial infarction (hazard ratio [HR] 1.88, 95% CI 1.78–2.07), ischemic stroke (HR 3.02, 95% CI 2.66–3.43), hospitalization for bleeding (HR 1.98, 95% CI 1.81–2.16) and, in particular, death (HR 4.48, 95% CI 4.21–4.77) than non-bleeders with a low-to-moderate predicted risk (CHADS-P2A2RC score &amp;lt;4). Conclusions Patients with CCS experiencing a bleeding event during the first year after first-time PCI had a substantially higher long-term risk of death and recurrent bleeding, but not a higher risk of ischemic events. Therefore, bleeding events during the first year after PCI may guide the preclusion of selected patients from long-term dual antithrombotic therapy. Among non-bleeders, the risk of ischemic events rose proportionately more than the risk of bleeding when comparing high-risk with low-risk patients. This is an important finding for clinicians, for whom accurate identification of patients at highest risk of ischemic events is an essential step in treatment allocation. Funding Acknowledgement Type of funding sources: None.