Risk Of Ischemic Events Research Articles

Individualized antiplatelet therapy for non-cardiogenic ischemic stroke

ObjectiveThis research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. MethodsAmong a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. ResultsThe individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. ConclusionIndividualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.

The Association of CHADS-P2A2RC Risk Score With Clinical Outcomes in Patients Taking P2Y12 Inhibitor Monotherapy After 3 Months of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention.

Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs. prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADS-P2A2RC, after percutaneous coronary intervention (PCI). This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358-6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868-3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). The CHADS-P2A2RC risk score is valuable in discriminating high-ischemic-risk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT. ClinicalTrials.gov Identifier: NCT02079194.

Ticagrelor vs clopidogrel when coadministered with bivalirudin in patients with acute coronary syndrome undergoing percutaneous coronary intervention

BackgroundThe optimal perioperative antithrombotic strategy for patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI) remains controversial. ObjectivesTo determine the safety and effectiveness of bivalirudin plus ticagrelor vs bivalirudin plus clopidogrel in patients with ACS undergoing PCI in the real world. MethodsBetween March 2016 and March 2019, 7234 patients with ACS who had undergone PCI, received bivalirudin periprocedurally, and were prescribed ticagrelor or clopidogrel were enrolled in a single-center, all-comer, modern, retrospective cohort study. Incidence rates of 12-month ischemia (cardiac death, myocardial infarction, or stroke), all-cause death, Bleeding Academic Research Consortium (BARC) type 2,3,5 bleeding, and BARC type 3,5 bleeding were compared between different groups. ResultsIn total, 4960 patients received bivalirudin plus clopidogrel and 2274 patients received bivalirudin plus ticagrelor. Compared with bivalirudin plus clopidogrel, bivalirudin plus ticagrelor was associated with lower ischemic events (1.74% vs 2.84%; relative risk, 0.61; 95% CI, 0.41-0.91; P = .02) and stroke (0.05% vs 1.01%, P < .001) within 12 months after PCI without excessive risk of bleeding (BARC type 2,3,5 bleeding: 4.49% vs 3.76%, P = .22; BARC type 3,5 bleeding: 2.84% vs 2.02%, P = .08). The beneficial effects of bivalirudin plus ticagrelor were consistent among subgroups. ConclusionAs an initial treatment strategy, bivalirudin plus ticagrelor could reduce the 12-month risk of ischemic events compared with bivalirudin plus clopidogrel significantly without increasing the bleeding risk in ACS patients undergoing PCI.

Prolonged dual antiplatelet therapy in invasively treated acute coronary syndrome patients with different lipoprotein(a) concentrations.

Lipoprotein(a) [Lp(a)] was positively associated with recurrent ischemic events in patients with acute coronary syndrome (ACS). This study was performed to investigate the effect of Lp(a) levels on outcomes of dual antiplatelet therapy (DAPT) > 1 year versus DAPT ≤ 1 year after percutaneous coronary intervention (PCI) in this population. A total of 4,357 ACS patients who were event-free at 1 year after PCI were selected from the Fuwai PCI Registry, and patients were stratified into four groups according to DAPT duration (≤ 1 year vs. > 1 year) and Lp(a) levels (≤ 30 mg/dL vs. > 30 mg/dL). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of cardiac death, myocardial infarction or stroke. After 2.4-year follow-up, the incidence of MACCE (HRadjusted 0.284, 95% CI 0.115-0.700; HRIPTW 0.351, 95% CI 0.164-0.751) were significantly reduced in DAPT > 1 year group than that in DAPT ≤ 1 year group in individuals with elevated Lp(a) levels. However, in individuals with normal Lp(a) levels, no statistically difference was found between these two groups in terms of MACCE, although the risks of all-cause death and definite/probable stent thrombosis were lower in DAPT > 1 year group. Notably, the risk of clinically relevant bleeding did not statistically differ between these two groups in individuals with different Lp(a) levels. This study firstly demonstrated that extended DAPT (> 1 year) was statistically associated with lower risk of ischemic events in ACS patients with elevated Lp(a) levels after PCI, whereas this association was not found in individuals with normal Lp(a) levels.

The effects of CYP2C19 genotype polymorphism and clopidogrel resistance on ischemic event occurrence in patients with peripheral arterial disease undergoing revascularization: A prospective cohort study

IntroductionPeripheral arterial disease (PAD) affects approximately 236 million people worldwide. Therefore, this study aimed to investigate the relationship between CYP2C19 genotype polymorphisms and clopidogrel resistance (CR) following revascularization in patients with PAD. Materials and methodsIn total, 345 patients who underwent PAD revascularization were monitored for five years and risk factors for ischemic events were identified. Platelet reactivity and CYP2C19 genotypes were measured, and patients were classified as normal, intermediate, or poor metabolizers based on their genotypes. The study endpoint was defined as an ischemic event, that encompassed major adverse cardiovascular or limb events, or all-cause death. ResultsIn this study, ischemic events following PAD revascularization were associated with patient age, prior minor amputation, the Rutherford category before revascularization, indications for revascularization, index ankle-branchial index before revascularization, CYP2C19 phenotypes, and CR. Intermediate and poor metabolism, the Rutherford category before revascularization, and CR were independent risk factors for ischemic events in patients after PAD revascularization. Similarly, intermediate and poor metabolism, the Rutherford category before revascularization, and CR were independent risk factors for ischemic events in patients with PAD after revascularization within five years. Intermediate and poor metabolizers had a higher platelet reactivity and risk of CR than normal metabolizers. However, poor metabolizers had a higher platelet reactivity and risk of CR than intermediate metabolizers. Furthermore, the hazard ratio for ischemic events increased with platelet reactivity. This effect was more prevalent in intermediate and poor metabolizers than in normal metabolizers. ConclusionsIschemic events in patients after PAD revascularization were affected by independent risk factors. Decreased clopidogrel metabolism increased the platelet reactivity and CR in patients after PAD revascularization. Furthermore, high platelet reactivity was associated with an increased risk of ischemic events in patients with intermediate and poor metabolism.

Frequency and Prognostic Value of Acute Periprocedural Myocardial Injury in Elective Percutaneous Coronary Interventions

Background. Periprocedural myocardial injury (PMI) is an acute complication of percutaneous coronary interventions (PCI) in patients with stable coronary artery disease. Its frequency and relationship with the prognosis of the disease are especially important in elective interventions due to the low risk of ischemic events in this cohort of patients. However, according to the literature, there are significant differences in the criteria for PMI and type 4a myocardial infarction (MI), and, accordingly, their frequency and their prognostic value. Aim. To study the frequency and magnitude of PMI during elective PCI in terms of the level of periprocedural increase in cardiospecific biomarkers, as well as to determine the relationship of PMI with long-term adverse events in patients with chronic coronary artery disease. Materials and methods. A single-center open retrospective cohort study was conducted, which included 435 patients (367/84.4 % men, mean age 58.3±8.6 years) from the elective PCI registry. PMI was diagnosed with an increase in the level of creatine phosphokinase MB fraction (CK-MB) or or cardiac troponin I (cTn I) &gt;1×99 percentile URL (Upper Reference Limit), while the level of increase in biomarkers &gt;1, 2, 3, 4 or &gt;5×99 percentile URL was recorded. An increase in biomarkers &gt;5x99 URL percentile was assessed as a large PMI, and in the presence of clinical and imaging evidence of new loss of viable myocardium, as periprocedural MI type 4a. Depending on the level of periprocedural increase in biomarkers, the relative risk (RR) of developing long-term (within 5 years after index PCI) adverse cardiovascular events, death, as well as clinically significant bleeding and newly diagnosed malignant oncological diseases was calculated. In addition, the correlation between PMI and the above endpoints was summarized using Kaplan-Meier analysis. Results. The frequency of periprocedural PMI diagnosed by increased biomarkers &gt;1×99 percentile URL was 40.2 %, &gt;2×99 percentile URL — 9.7 %, &gt;3×99 percentile URL — 6.7 %, &gt;4×99 percentile URL — 4.8 %, &gt;5×99 percentile URL — 3.5 %, type 4a MI — in 2 patients (0.46 %). An association of “major” PMI (&gt;5x99 percentile URL) with cardiovascular complications within 3 years after elective PCI, including fatal ones, was revealed: for acute myocardial infarction (AMI), RR — 6.516, confidence interval (CI) [2.375-17.881]; for death from cardiovascular causes RR — 6.538, CI [1.695-25.227]. An association of “moderate” PMI (&gt;3, but &lt;5 ×99 URL percentile) with acute ischemic events within 3 years after elective PCI was shown: for AMI, RR was 4.073, CI [1.598 — 10.378]. An association of “minor” AKI (&gt;1, but &lt;5 ×99 URL percentile) with acute ischemic events within 3 years after elective PCI was shown: for AMI, RR was 4.073, CI [1.598 — 10.378]. An association of “minor” AKI (&gt;1, but &lt;3 ×99 URL percentile) with newly diagnosed malignant oncological diseases within 5 years after index PCI was revealed: RR 2.319; CI [1.248- 4.310]. An association of late thrombotic events, such as stent thrombosis (index and re-interventions), stent occlusion (index and non-index) as a reason for re-intervention within 5 years after index PCI, was found with most PMI subgroups. Kaplan-Meier analysis of the dependence of clinically significant bleeding within 5 years after index PCI on the development of “moderate” PMI (p=0.003), as well as the association of non-cardiovascular death within 5 years after index PCI with “minor” PMI (p= 0.007). Conclusion. Registration of periprocedural increase in cardiac biomarkers should be carried out during planned PCI not only for the purpose of diagnosing and predicting acute and late ischemic events, but also for assessing the risk of developing stent occlusion, clinically significant bleeding and prognostically important comorbidities in the long-term (5-year) period in order to identification of groups of patients requiring active monitoring, additional examination and selection of an optimal treatment regimen at the outpatient stage of rehabilitation.

Outcomes after TAVI in patients with atrial fibrillation and a history of recent PCI: Results from the ENVISAGE-TAVI AF trial.

Patients with atrial fibrillation (AF) and a recent (≤ 90days) percutaneous coronary intervention (PCI) undergoing transcatheter aortic valve implantation (TAVI) are at high bleeding risk due to the addition of oral antiplatelet (OAP) agents on top of oral anticoagulants. Data on outcomes of these patients are needed to optimize antithrombotic treatment. This analysis compared annualized clinical event rates in patients with and without a recent PCI enrolled in ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban and vitamin K antagonists in AF patients after TAVI. The primary efficacy and safety outcomes were net adverse clinical events (NACE) and major bleeding. Overall, 132 (94.3%) patients with a recent PCI (n = 140) received OAP after TAVI, compared with 692 (55.9%) patients without a recent PCI (n = 1237). Among patients with a recent PCI on OAP agents, use of dual antiplatelet therapy decreased to 5.5%, and use of single antiplatelet therapy (SAPT) increased to 78.0% over 3months post-randomization. Conversely, use of SAPT predominated at all time points in patients without a recent PCI history. There were no significant differences in the incidence of NACE or other outcomes assessed, except for major bleeding events, which were more frequent in patients with vs without a recent PCI history (hazard ratio [95% confidence interval]: 2.17 [1.27, 3.73]; P = 0.005). Patients with AF undergoing TAVI with a recent PCI have a similar risk of ischemic events and mortality, but an increased risk of major bleeding compared with patients without a recent PCI.

Predictive value of ApoB/ApoA-I for recurrence within 1 year after first incident stroke.

ApoB/ApoA-I ratio is a reliable indicator of cholesterol balance, particularly in the prediction of ischemic events risk. The aim of this study was to investigate the prognostic value of ApoB/ApoA-I for stroke recurrence within 1 year after the first incident. We retrospectively included patients who were first diagnosed with acute (<7 days after onset) ischemic stroke. Blood samples were collected on admission, and serum ApoB and ApoA-I concentrations were measured. We analyzed the relationship between ApoB/ApoA-I ratio and ischemic stroke recurrence within 1 year. A total of 722 patients with acute ischemic stroke were included, of whom 102 experienced stroke recurrence within 1 year, with a recurrence rate of 14.1%. Serum ApoB/ApoA-I concentrations on admission were higher in patients with stroke recurrence at 1 year compared with those with a good prognosis (P < 0.001). The Kaplan-Meier survival curve revealed a significant difference in cumulative stroke recurrence rates across ApoB/ApoA-I tertiles (log-rank P-value < 0.001). A positive correlation between the ApoB/ApoA-I ratio and the risk of stroke recurrence within 1 year was demonstrated using Cox regression analysis, which remained significant after adjusting for traditional risk factors [hazard ratio (HR) 4.007, 95% confidence interval (CI) 1.661-9.666]. This relationship was particularly strong in patients with LAA stroke (HR 4.955, 95% CI 1.591-15.434). Subgroup analysis further revealed that a high ApoB/ApoA-I ratio was strongly associated with stroke recurrence regardless of whether patients had high or low LDL-C levels. ApoB/ApoA-I ratio, measured during the acute phase of the first stroke, was positively correlated with the risk of stroke recurrence within 1 year.

Assessing the efficacy of VerifyNow platelet-function testing in predicting postoperative thromboembolic complications of neuroendovascular surgery: A systematic review and meta-analysis (part 1).

Despite the heavily debated use of routine platelet-function testing, the VerifyNow Platelet Reactivity Unit (PRU) assay has been increasingly adopted as standard of care for assessing risk of postoperative thromboembolic complications of neuroendovascular surgery. We conducted a systematic review and meta-analysis to examine the relationship between platelet response and risk of ischemic events from neuroendovascular surgery, assess the efficacy of point-of-care platelet-function testing in predicting thromboembolic outcomes, and assess whether a clinically useful threshold for platelet response can be defined in order to standardize guidelines. PubMed, Embase, and Scopus were searched. Following deduplication, articles were first screened for relevance by title and abstract, followed by full text. Of 735 resultant articles, 22 studies consisting of 3266 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 45.8% were treated with flow diversion, 16.4% with stent-assisted coil embolization, 15.8% with intracranial stenting, 12.0% with simple coil embolization, 3.4% with balloon-assisted coil embolization, 3.6% with extracranial stenting, and 3.0% with an alternate method. 54.5% (12/22) of studies determined platelet hyporesponse to be an independent predictor of postoperative thromboembolic complications, with 27.3% (6/22) of studies reporting a similar, but non-statistically significant trend. 18.2% (4/22) of studies found no relationship between platelet response and postoperative thromboembolic complications. The estimated clinical threshold for PRU to prevent thromboembolic complications varied greatly across studies (Range: > 144-295 PRU). Meta-analysis found platelet hyporesponse to have a 2.23-fold increased risk of thromboembolic complications compared to normoresponders (RR = 2.23, P = 0.03). While PRU demonstrates a significant predictive value for postoperative thromboembolic complications of neuroendovascular surgery, the target therapeutic threshold for minimizing ischemic events remains unclear. Further studies, such as large multicenter cohorts of the existing data, are needed to standardize guidelines.

A rare anatomical variation of the circle of Willis in a patient with an ischemic stroke

Purpose &#x0D; The cerebral arterial circuit provides collateral circulation to the brain and protects the brain from ischemia, by sustaining tissue perfusion in case of reduced or impaired blood flow through its branches. Although many random anatomical variations in the circle of Willis (CoW) are of minor importance, some increase the risk of ischemic events, aneurysm, and atherosclerosis, and play an important role in endovascular and surgical treatment planning. &#x0D; Case presentation &#x0D; We report a rare arterial variation of the CoW diagnosed by computed tomography angiography in a patient with ischemic stroke. We found aplasia of the A1 segment of the left anterior cerebral artery and ipsilateral hypoplasia of the P1 segment of the left posterior cerebral artery. &#x0D; Conclusion &#x0D; For neurosurgeons, neurologists, and neuroradiologists, detailed knowledge of the numerous anatomical variations in the arterial supply to the brain is crucial to make a correct diagnosis and choose the appropriate treatment. The type of CoW variation influences stroke severity and outcome, with an incomplete CoW related to more severe conditions (higher National Institutes of Health Stroke Scale scores, more severe neurological deficits, and worse neurological outcomes) and poor prognosis.

Differential Impact of Clinical Factors for Predicting High Platelet Reactivity on Clinical Outcomes in Acute Myocardial Infarction Patients Treated With Clopidogrel and Prasugrel.

Several scoring systems, including the ABCD-GENE and HHD-GENE scores incorporating clinical and genetic factors, have been developed to identify patients likely to have high platelet reactivity on P2Y12 inhibitors, leading to increased risks of ischemic events. However, genetic testing is not widely available in daily practice. We aimed to evaluate the differential impact of clinical factors in the scores on ischemic outcomes in patients treated with clopidogrel and prasugrel. This bi-center registry included 789 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention and treated with either clopidogrel or prasugrel at discharge. The relations of the number of clinical factors included in the ABCD-GENE (age ≥ 75 years, body mass index ＞30 kg/m2, chronic kidney disease, and diabetes) and HHD-GENE (hypertension, hemodialysis, and diabetes) scores to the primary endpoint of major cardiovascular events after discharge, a composite of death, recurrent MI, and ischemic stroke, were evaluated. The number of clinical factors in the ABCD-GENE score was not predictive of ischemic outcomes after discharge in patients treated with clopidogrel and/or prasugrel, while the increase in the number of clinical factors of the HHD-GENE score was associated with an increased risk of the primary endpoint in a stepwise manner in patients on a P2Y12 inhibitor. Clinical factors listed in the HHD-GENE score may help stratify ischemic risks in patients with acute MI treated with clopidogrel and prasugrel, whereas risk stratification without genetic testing in patients treated with clopidogrel may be challenging.

Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial

BackgroundIn the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. ObjectivesThe authors analyzed separately the outcomes of INV patients treated with PCI or CABG. MethodsPatients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. ResultsAmong INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). ConclusionsIn ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs.

Intensity of dual antiplatelet therapy based on thrombotic and bleeding risks after coronary stenting

Abstract Background/Introduction High thrombotic risk (HTR) features are associated with higher ischemic rate, which may be mitigated by potent antiplatelet therapy. However, concomitant high bleeding risk (HBR) may be present, making it unclear whether the intensity of antiplatelet therapy should be prioritized. Purpose This study investigated the prognostic implications of HTR and HBR strata according to intensity of antiplatelet therapy (indicated by platelet reactivity) after coronary stenting. Methods HTR was defined as having at least one of the three risk factors: 1) index presentation with acute coronary syndrome; 2) complex coronary artery disease and stenting; and 3) guideline-directed clinical ischemic risk factors. HBR was determined according to presence of Academic Research Consortium (ARC)-HBR criteria. In addition, high platelet reactivity (HPR) was decided depending on the level of platelet reactivity (&amp;gt; 208 P2Y12 reaction unit measured by VerifyNow assay). Results Among 4,550 patients, HTR features were observed in 3,973 patients (87.3%) and 1,451 (31.9%) met the ARC-HBR criteria. HPR phenotype (n=2563, 56.3%) significantly increased the risk of 4-year ischemic events (adjusted hazard ratio [HRadj]: 1.40; 95% confidence interval [CI]: 1.15-1.70; P=0.001). Among patients who met the ARC-HBR criteria, HPR was not associated with the rate of ischemic events, regardless of HTR features. In cases of non-HBR patients, HPR phenotype increased ischemic events only in patients with HTR feature(s), which risk proportionally increased according to the number of HTR features (HRadj: 0.67, 1.47 and 1.58; 95% CI: 0.22-2.08, 0.94-2.29 and 1.09-2.28 in 0 [9.2%], 1 [31.2%] and ≥2 [27.7%] HTR features). In HBR patients, the risk of major bleeding was not increased by the level of antiplatelet effect. Conclusion HPR phenotype was significantly associated with the risk of ischemic events after coronary stenting, which proportionally increased according to the number of HTR features only if the ARC-HBR criteria were not present. These observations suggested that when concordant, bleeding risk, more than ischemic risk, should inform decision-making on the intensity of antiplatelet therapy.KM curve and HR forest plot for MACCEKM curve and HR forest plot for NACE

Risks and benefits of antiplatelet therapy in patients with abdominal aortic aneurysm without symptomatic atherosclerotic disease: a nationwide cohort study

Abstract Background Patients with abdominal aortic aneurysm (AAA) suffer a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapies to mitigate this risk. However, in patients with AAA and no symptomatic atherosclerosis, the benefit of antiplatelet is sparsely investigated. Purpose To assess the effectiveness of antiplatelets vs no antiplatelets on the risk of ischemic events (composite of myocardial infarction and ischemic stroke) and bleeding in individuals with AAA who had no concomitant atherosclerotic vascular disease. Methods We designed a target trial to compare outcomes among treatment initiators and non-initiators and emulated the trial contingent on patient eligibility at time of inclusion, utilizing Danish nationwide observational data from January 2010 through August 2021. Confounding was handled by means of inverse probability treatment weighting based on the propensity score. The emulated sequential trial results for all possible trial months were pooled by means of pooled logistic regression models to estimate the intention-to-treat average treatment effects, and the 5-year associated treatment differences were expressed as hazard ratio (HR) with 95% confidence intervals (CI) and estimated event-free survival. Results A total of 6,344 patients provided 131,047 trial participants: 3,363 of these were new initiators of antiplatelet therapy, while 127,684 were non-initiators. During a median follow-up of 24 months, 173 and 369 ischemic events occurred among initiators and non-initiators, respectively. The corresponding HR of 0.91 (CI 95% 0.73 to 1.17) and an estimated absolute event-free survival difference of -0.6% (Figure 1). For bleeding, the HR was 1.26 (CI 0.97 to 1.58) and the event-free survival difference was 1.0%. Conclusion This target trial emulation, using nationwide observational data on all patients with AAA and no record of symptomatic atherosclerotic disease, did not find evidence of antiplatelets to lower the risk of ischemic events, but also no evidence of substantial higher bleeding risk. The observed differences between the treatment groups were minimal, suggesting limited clinically relevance of this treatment.ischemia- and bleeding free survival

Lipoprotein(a) and the risk of major adverse limb events in patients with stable atherosclerotic vascular disease

Abstract Background/Introduction Patients with atherosclerotic vascular disease are at heightened risk of ischemic events, including adverse limb events. The pathobiology of adverse limb events ranges from events that are predominantly thrombotic such as acute limb ischemia (ALI) to those that are due primarily to progressive atherosclerosis such as worsening functional imitation requiring elective peripheral revascularization and development of critical limb ischemia (CLI). Evolving data suggest that lipoprotein(a) [Lp(a)] may be associated with the risk of adverse limb events; however, which type of events are related to Lp(a) has not been well described. Purpose To evaluate the association between Lp(a) and specific limb outcomes in patients with stable atherosclerotic vascular disease. Methods Data from two randomized clinical trials including patients with stable atherosclerotic vascular disease were combined: TRA2P-TIMI 50 and FOURIER. We measured Lp(a) in baseline samples in the TIMI Clinical Trials Laboratory. Major adverse cardiovascular events (CV death, myocardial infarction (MI), or stroke) were the primary or key secondary outcomes of the trials. Peripheral revascularization procedures occurring during follow up were investigator reported. Adverse limb events, including CLI and ALI, were categorized through the review of safety data by two blinded vascular specialists. MALE was defined as the composite of peripheral revascularization, CLI, or ALI. The association of Lp(a) as a continuous variable and MALE was assessed and adjusted for randomized therapy in each trial, age, sex, race, region, prior MI, prior stroke, peripheral artery disease, hypertension, diabetes mellitus, smoking status, and statin use. Results A total of 28,892 patients were included in the combined analysis population. The median Lp(a) was 36 nmol/L (IQR 12 – 159). A total of 1336 MALE events occurred during follow-up, including 1307 peripheral revascularizations (1237 elective, 173 urgent), 259 CLI events, and 148 ALI events. Lp(a) was associated with an increased risk of MALE (Adj HR 1.07 per SD, 95% CI 1.02 – 1.13, p=0.007, Figure Panel A) with the risk of a similar magnitude for that of MACE (Adj HR 1.05 per SD, 95% CI 1.01 – 1.10, p=0.020). The association of Lp(a) and MALE was driven by peripheral revascularizations including elective revascularization (Adj. HR 1.07, 95% CI 1.02 – 1.13, p=0.010) with a consistent trend for CLI; however, a relationship with ALI was unclear (Figure Panel B). Conclusion In patients with stable atherosclerotic vascular disease, Lp(a) is associated with MALE with the relationship driven by peripheral revascularization and a consistent trend for CLI. Any relationship with ALI, a primarily thrombotic event, is less clear. Overall, these data support the relationship of Lp(a) and progression of lower extremity atherosclerosis.Figure Panel AFigure Panel B

Is pre-diabetes a predictor of events in patients with atrial fibrillation?

Abstract Introduction Diabetes mellitus (DM) not only increases the probability of presenting atrial fibrillation (AF), but it is also a predictor of ischemic stroke included in scales such as CHA2DS2VASc. However, there is limited information on the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or hemorrhagic events in patients with pre-diabetes and AF. Objectives This study aimed to investigate whether the presence of pre-diabetes in patients with AF increases the risk of ischemic events, hemorrhagic events, myocardial infarction or death. Methods We used data from the CardioCHUVI-AF registry, which included 18,285 patients with AF from a Galician health area between January 2014 and December 2019. Patients with valvular AF (n=376), with loss of follow-up (n=97), without information on baseline characteristics (n=48) and without data on HbA1c (12,473) were excluded. The final cohort consisted of 5,291 patients, 2,993 were non-diabetics (56.6%) and 2,298 with known diabetes (43.4%). This final cohort was classified according to HbA1c in diabetics if HbA1c is more than 6.5% (n= 1,546; 29.2%), pre-diabetics when HbA1c is between 5.7 and 6.4% (n =2,233; 42.2%) and non-diabetics if HbA1c was less than 5.7% (n = 1,512; 28.6%). Competing hazards regression analysis for non-fatal events (with death as the competing event) and conventional Cox regression for mortality were performed. Results 2,993 non-diabetic patients with AF and HbA1c data were followed for 4.1 ± 1.6 years. The mean age was 73.0 ± 9.9 years, 47.4% were women, the mean CHA2DS2VASc score was 2.9 ± 1.4 points, the mean HASBLED score was 2.5 ± 1.2 points, and 2,407 (80.4%) patients were under treatment with oral anticoagulants. In the Kaplan Meier curves, no was observed a higher rate of events in pre-diabetes patients in comparison with patients with normal glycemia. In the multivariate analysis, after adjusting for the CHA2DS2VASc and HASBLED scales, as well as for anticoagulant therapy, it was observed that pre-diabetes was not associated with an increased risk of mortality ( HR= 0.80; 95% CI, 0.60-1.08), ischemic stroke (HR= 0.99; 95% CI, 0.71-1.38), major hemorrhage (HR= 0.78; 95% CI, 0.60-1.02) or myocardial infarction (HR= 1.08; 95% CI, 0.65-1.79), compared with patients with normal glycemia. Conclusions In our registry, non-diabetic patients with atrial fibrillation do not have a higher risk of events when their glycated hemoglobin is in the pre-diabetes range.

Meta-analysis of 3-month vs 12-month dual anti-platelet therapy after percutaneous coronary intervention

Abstract Background The optimal duration of dual antiplatelet therapy (DAPT) in the era of second generation drug-eluting stents is a matter of debate as increasing evidence suggests that shorter periods of DAPT are feasible and reduce bleeding events. However, the non-inferiority design of the published trials regarding ischemic events still raises doubt on its effectiveness. Methods We performed a meta-analysis to evaluate short-term (≤ 3 months) vs long-term (≥ 12 months) DAPT after percutaneous coronary intervention (PCI). PubMed, Embase and Cochrane Central were searched from inception to February 2023 to identify randomized controlled trials that compared outcomes of patients between these two regimens. Primary outcome of interest included a composite of ischemic events (cardiovascular death, myocardial infarction, re-revascularization and stroke) and secondary outcome was major bleeding as assessed by Bleeding Academic Research Consortium (BARC) classification ≥ 3 after 1 year of follow up. Event rates were extracted and Mantel-Haenszel fixed-effects model was used to perform the meta-analysis. Results We identified a total of 5 trials with 18.682 randomized patients. The use of short-term DAPT was not associated with increased risk of ischemic events (0.90 [0.75-1.08], p=0.250; Figure 1) and was associated with reduced risk of major bleeding (0.74 [0.65-0.84], p&amp;lt;0.001; Figure 2). Conclusion The present meta-analysis provides an updated data on the use of DAPT duration. Short-term DAPT appears to be equivalent to long-term DAPT regarding ischemic risk and a superior strategy in optimizing bleeding risk reduction.Forest plot of ischemic outcomesForest plot of bleeding outcomes

Glut4 expression in pro-atherogenic monocytes is associated with estrogen induced ROS formation

Abstract Background Glucose transporter (GLUT) 4 was shown to be expressed on monocytes with dynamic alterations. Moreover, increased formation of monocyte related reactive oxygen species (ROS) is an important marker for atherosclerosis and estrogen is known to increase ROS. However, the impact of estrogen on human monocytes have not been investigated. This is of great importance as a high number of aging women receive hormone replacement therapy (HRT) due to meno-pause symptoms. This was shown to be associated with high risk for ischemic events. In this study, we investigated the impact of estrogen on human monocytes about membrane expression of GLUT4 and ROS formation. Methods In this pilot study, we investigated human leukocytes from 88 healthy volunteers (54 female and 34 male) and 114 patients (56 female and 58 male) treated in the department of Cardiology, Pneumology and Vascular medicine, University Hospital Düsseldorf. Buffy coat was extracted out of whole blood by centrifugation and analysed by flow-cytometry. Amount of CD14+ and CD16+ monocytes was measured in % of all leukocytes in all participants. ROS and GLUT4 expression were assessed for monocyte type in dependence from increasing estrogen concentrations in a sub cohort by in-vitro incubation representing physiological peak and HRT concentrations (0, 500 and 2000 pM). Results Mean age of healthy volunteers was 31,2 years. Mean age of patients was 75,9 years. In patients, 51% were male, 58% had arterial hypertension, 33% diabetes mellitus type II, 16% were smokers and 19% were obese. Antiatherogenic monocytes (CD16+) were stable in males but decreased with age in females (female: r=-0.3130 p=0.0010; male: r=-0.1011 p=0.3946). In contrast, pro-atherogenic monocytes (CD14+) increased with age in females (female: r=0.4013 p=&amp;lt;0.0001; male: r=0.09135 p=0.4389). Increasing estrogen concentrations induced ROS formation in all monocytes in a dose dependent manner (0 – 947±124, 500 - 1312±258, 2000 - 1248±629 geometric mean, p=0.0327 [one-way ANOVA]). Separation in CD14+ and CD16+ monocytes revealed that this effect was only driven by increase in CD14+ monoctyes (0 - 1021±325, 500- 1160±239, 2000 – 513 geometric mean, p=0.0179), whereby CD16+ monocytes did not show relevant increase. GLUT4 membrane expression was inversely related to increasing estrogen levels with decrease in CD14+ (0 - 578±81, 500- 498±55, 2000- 507±41 geometric mean, p=0.0131) and numerical reduction in CD16+ monocytes by high estrogen levels (0- 592±77, 500 - 544±80, 2000- 537±72 geometric mean, p=0.0784) Conclusion In this study, we could show that high estrogen levels induce decrease of GLUT4 membrane expression in human monocytes. This might be associated with increased ROS formation in pro-atherogenic CD14+ monocytes which are already increased with age in women. This might reflect a relevant mechanism for the increased rate of ischemic events by HRT.

Hemostasis Biomarkers and Long-Term Risk of Recurrent Cardiovascular Events and Bleeding Complications in Young Patients with an Ischemic Stroke

Background: Patients with ischemic stroke at a young age (18-50 years) have a persistent increased risk of recurrent ischemic cardiovascular events, despite antithrombotic treatment. Additionally, antithrombotic agents result in a higher risk of bleeding complications. Balancing hemostasis to prevent thrombotic events and minimizing the risk of hemorrhagic events is challenging. Previous research observed a hypercoagulable state and a significant degree of inflammation years after an acute ischemic stroke in young adults. It is known that an increased clotting tendency is a risk factor for a first ischemic stroke, especially in young adults. However, the risk profile of a recurrent event in these individuals can be different. To this end, our study aims to investigate the role of plasma pro- and anticoagulation biomarkers, platelet activation markers and thrombin generation parameters in the risk of recurrent ischemic arterial events and bleeding complications after a first ischemic stroke or transient ischemic attack (TIA) at a young age. Method: Patients from a single-center cohort study (the FUTURE cohort) with a first-ever TIA or ischemic stroke event between 1980 and 2010 were included. Blood was collected in 2010 and patients were followed on recurrent ischemic events or bleeding complications between 2010 and 2023. The following coagulation parameters were measured: blood cell count, Von Willebrand factor, active Von Willebrand factor, factor VIII, prothrombin, fragment 1.2, d-dimer, fibrinogen, fibrin degradation products, antithrombin, alpha-2-macroglobulin, serum CXCL-4 and CXCL-7. In addition, thrombin generation (TG) was determined using 1pM and 5pM tissue factor, and thrombomodulin in platelet-poor plasma to assess the functional capacity of plasma to form thrombin. The primary outcome was a composite of recurrent ischemic stroke, TIA, acute coronary syndrome or peripheral artery disease. The secondary outcome was the occurrence of a bleeding complication using the Bleeding Academic Research Consortium (BARC) criteria. We applied Cox proportional hazard models to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results : Among 378 patients (median age 42.1 years, 56% women), 74 experienced a recurrent ischemic event during a mean follow-up of 6.5 years. An increased platelet and leukocyte count, along with elevated levels of fragment 1.2, fibrinogen and D-dimer were associated with a higher risk of ischemic events (table 1). Patients with low plasma antithrombin activity had a higher risk of recurrent ischemic events, especially in women (HR 0.67 [0.47-0.96]). After adjustment for age, sex and traditional risk factors, the association between leukocytes numbers, fragment 1.2 and fibrinogen levels and antithrombin activity and the risk of recurrent ischemic events remained: HR 1.14 [1.05-1.25], 1.07 [1.01-1.14], 0.80 [0.65-0.98], and 1.09 [1.00-1.17], respectively. In patients without vitamin K antagonist treatment, the association between antithrombin activity (HR 0.78 [0.62-0.98]) and leukocytes numbers (HR 1.15 [1.05-1.25]) with recurrent ischemic events were stronger. Thrombin generation parameters were not related to recurrence. Bleeding complications were observed in 16% of patients, mainly among women and predominantly attributable to gynecological bleedings. Hemoglobin, platelets, CXCL-4 and -7, prothrombin, fragment 1.2 and alpha-2-macroglobulin were associated with a bleeding complication (table 2). The association for platelets (HR 0.93 [0.89-0.97]), CXCL-4 (HR 0.90 [0.82-0.99]) and alpha-2-macroglobulin (HR 1.15 [1.03-1.29]) remained after adjustment. Conclusion: Lower antithrombin activity and, higher fragment 1.2, fibrinogen levels, and leukocytes counts were linked to an increased risk of recurrent ischemic events. Bleeding was associated with platelets, CXCL4, and alpha-2-macroglobulin. Overall, especially platelets appear to be significantly involved in the risk of both recurrent arterial thrombosis and bleeding, whereas the observed association with risk of recurrent ischemic events implies a more dominant role of the coagulation system.

Role of Cardiac Risk Scores in Clinical Use to Predict Outcomes of Acute Ischemic Stroke.

Acute coronary syndromes and ischemic stroke have similar risk factors. Risk scores help to identify disease severity in both diseases. We aimed to evaluate if HEART (History, ECG, Age, Risk factors, and Troponin) score could predict re-hospitalization, recurrent cardiac/cerebrovascular events risk, and mortality within 1-year follow-up in patients presenting with acute ischemic stroke. Patients hospitalized with a diagnosis of acute ischemic stroke in our tertiary center between 2019 and 2021 were included in this retrospective study. CHA2DS2-VASc and HEART scores on admission were calculated. In-hospital, 1-month, and 1-year mortalities, as well as re-hospitalization due to recurrent ischemic (cardiac/cerebral), were defined as major adverse cardiac and cerebrovascular events (MACCE), and occurrence of MACCE was accepted as the primary endpoint of the study. Comparative statistical and regression analyses were obtained. A total of 297 patients were included. The mortality rate for 30 days was 7.4% and 1 year was 20.5%. HEART and CHA2DS2-VASc scores were found independent risk factors associated with the occurrence of MACCE. Patients who experienced MACCE had higher HEART and CHA2DS2-VASc scores. Meanwhile, HEART score had better prognostic accuracy than CHA2DS2-VASc score when a cutoff value of 3.5 was set, which is associated with 84.7% sensitivity and 75.2% specificity in the prediction of MACCE. HEART score is effective in determining re-hospitalization and recurrent cerebral ischemic event risk as well as mortality within 30 days and 1 year in patients presenting with acute ischemic stroke. Thus, concomitant use of HEART and CHA2DS2-VASc scores may provide better characterization of worse prognosis in ischemic stroke patients with high sensitivity and specificity.