After Acute Coronary Syndrome Research Articles

Extremely Low Activity of Serum Alanine Aminotransferase Is Associated with Long-Term Overall-Cause Mortality in the Elderly Patients Undergoing Percutaneous Coronary Intervention after Acute Coronary Syndrome

Background and Objectives: Recent studies revealed that the extremely low activity of serum alanine aminotransferase (ALT) is associated with frailty and contributes to increased mortality after acute physical stress. We aimed to investigate whether the extremely low activity of serum ALT (<10 U/L) at the time of diagnosis can be used to predict overall-cause mortality in elderly patients that underwent percutaneous coronary intervention (PCI) after acute coronary syndrome (ACS) diagnosis. Materials and Methods: A retrospective medical record review was performed on 1597 patients diagnosed with ACS who underwent PCI at a single university hospital from February 2014 to March 2020. The associations between the extremely low activity of serum ALT and mortality were assessed using a stepwise Cox regression (forward: conditional). Results: A total of 210 elderly patients were analyzed in this study. The number of deaths was 64 (30.5%), the mean survival time was 25.0 ± 18.9 months, and the mean age was 76.9 ± 7.6 years. The mean door-to-PCI time was 74.0 ± 20.9 min. The results of stepwise Cox regression analysis showed that the extremely low activity of serum ALT (adjusted hazard ratio: 5.157, 95% confidence interval: 3.001-8.862, p < 0.001) was the independent risk factor for long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. Conclusions: The extremely low activity of serum ALT at ACS diagnosis is a significant risk factor for increased long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. It is noteworthy that a simple laboratory test at the time of diagnosis was found to be a significant risk factor for mortality.

Addressing current challenges in optimization of lipid management following an ACS event: Outcomes of the ACS EuroPath III initiative.

Low-density lipoprotein cholesterol (LDL-C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However, LDL-C management for post-ACS patients remains challenging in clinical practice. The ACS EuroPath III project was designed to optimize LDL-C management in post-ACS patients by promoting guideline implementation and translating existing evidence into effective actions. Three surveys targeting cardiologists (n = 555), general practitioners (GPs; n = 445), and patients (n = 662) were conducted in Europe, with the aim of capturing information on patient characteristics and treatment during acute phase, discharge and follow-up. GPs' and patients' opinions on key treatment aspects were also collected. Based on survey results, international experts and clinicians identified areas of improvement and generated prototype solutions. Participants voted to select the most feasible and replicable proposals for co-development and implementation. Five key areas of improvement were identified: (1) inappropriate treatment prescribed at discharge; (2) lack of lipid guidance in the discharge letter; (3) inadequate lipid-lowering therapy (LLT) optimization; (4) gaps in guideline knowledge and lack of referral practices for GPs; (5) patients' concerns about lipid management. Proposed solutions for these focus areas included development of a treatment algorithm for the acute phase, a standardized GP discharge letter, an assessment tool for LLT efficacy at follow-up, an education plan for GPs/patients and a patient engagement discharge kit. The standardized GP discharge letter and treatment algorithm have been selected as the highest priority solutions for development. These initiatives have the potential to improve adherence to guidelines and patient management after ACS.

Adherence to Visits to Medical Institutions and Quality of Therapy after Acute Coronary Syndrome (according to the LIS Registry 3)

Aim. The aim of the research is to evaluate the relationship between patients' adherence to visiting polyclinics after acute coronary syndrome (ACS) and the quality of the therapy they receive.Material and methods. The study was conducted on the basis of the LIS registers (LIS and LIS-3) (Lyubertsy study of mortality) in the Lyubertsy district of the Moscow region. To clarify the vital status of all patients discharged in the first 9 months of 2014 and 2018. from Lyubertsy district hospital 2, contact was established no earlier than 1 year after discharge, and in case of death, its cause was clarified. In the course of a telephone survey, information was obtained on the therapy taken, adherence to visits to medical institutions, a record of cases of cardiovascular events and invasive treatment, hospitalizations due to worsening of the course of the underlying disease for the period after discharge from the hospital was carried out. The search for patients who did not answer the phone call was carried out by studying the archives of polyclinics, using the Megaclinic statistical database, and the data of the individual rehabilitation program for the disabled. In the course of a telephone survey, the response was 60.5%, the search for the remaining patients through statistical databases, the archive of polyclinics made it possible to increase the total response to 87.2%.Results. In the LIS-3 registry, out of 104 patients discharged in 2014, the status was determined in 90 (86.5%) patients, out of 223 patients in 2018 – in 195 (87.4%) patients. During the survey, it was found that 172 patients are observed after discharge from the hospital, 53 patients are not observed at all in the medical facility after discharge. 11 (4.9%) people did not take any groups of medications at the time of the survey. In the group of patients who are highly committed to attending a health facility, the best quality of taking essential medications after discharge from the hospital was noted according to the survey: statins (88.2%, p&lt;0.001), beta-blockers (86.4%, p&lt;0.001) and antiplatelets (90.9%, p=0.001). In both groups, committed and not committed to attending a medical facility, there is a negative dynamics in the quality of taking medications after discharge from the hospital, however, in the group of patients committed to attending a medical facility, it was noted that the odds of taking antiplatelet agents after discharge was 3.4 times higher (OR 3.449, p=0.002), beta-blockers – 4 times (OR 4.103, p&lt;0.001), statins – 4.5 times (OR 4.450, p&lt;0.001), in relation to the group of patients who are not observed in the medical facility after discharge from the hospital.Conclusion. 1-6 years after discharge from the hospital after the reference event, the quality of therapy deteriorated significantly in both groups, mostly in non-adherent patients. Significant differences in the quality of medication intake (antiplatelet agents, statins, β-blockers) were noted in the group of adherents to visiting health care facilities in comparison with those who were not committed to visiting health facilities. It is obvious that high adherence to visits to healthcare facilities after discharge from the hospital is associated with better quality of medication intake. Despite improvements in the quality of adherence to clinical recommendations, the percentage of patients who independently refuse to take drug therapy (4.9%), regardless of visits to healthcare facilities after discharge from the hospital, remains.

Participation and Prognostic Impact of Cardiac Rehabilitation After Acute Coronary Syndrome: Big-Data Study of the Korean National Health Insurance Service.

To investigate the actual rate and quality of cardiac rehabilitation (CR) participation in South Korea and its short-term impact on clinical outcomes after acute coronary syndrome (ACS). Data, including confirmed ACS diagnosis, socio-demographics, comorbidities, clinical outcomes, and CR claim codes, were collected from the Korean National Health Insurance Service claims database and compared between the CR and non-CR groups. Overall, 102,544 patients were included in the study, of which only 5.8% attended CR. Regarding testing, 83.6% of CR patients performed the cardiopulmonary exercise test, but follow-up testing was infrequently performed; in addition, 53.1% of them participated in an electrocardiogram monitoring exercise, but over half participated in only one session. After 1:1 propensity score matching, post-ACS cardiovascular events were significantly lower in the CR group than in the non-CR group. The cumulative 3-year hazard ratio for all-cause death was 0.612 (95% confidence interval [CI], 0.495-0.756), recurrent ACS was 0.92 (95% CI, 0.853-0.993), CR readmission was 0.817 (95% CI, 0.768-0.868), and major adverse cardiovascular events (MACE) was 0.827 (95% CI, 0.781-0.874) in the CR group. CR was associated with a significant dose-response effect on MACE, with a reduction in incidence from 0.854 to 0.711. The actual rate of CR participation in South Korea remains low, and participation quality was not outstanding despite National Health Insurance coverage. Nevertheless, the impact of CR on cardiovascular outcomes after ACS was significantly superior. Efforts to increase CR participation should be increased by establishing new CR facilities and strategies to resolve associated barriers.

Local-Regional In-Country Differences of Ischaemic Heart Disease – Forgotten or Overlooked

Objective: The number of cardiac interventions has increased massively and improved the outcome after cardiac events. The efforts during the last decades have proven effective with a falling incidence of new cardiovascular diseases. In a relatively uniform country with free tax supported medical treatment and a fully developed ambulance and helicopter service, percutaneous cardiac intervention (PCI) after acute coronary syndrome (ACS) or overall revascularization must be a good indicator of ischaemic heart disease (IHD) and geographical differences must reflect the area frequency of IHD. Thus, so far there has not been much focus on local in country differences, which could reveal new focus for treatments. Material and Methods: The mandatory Western Denmark Heart Registry (WDHR) was used to identify all adult cardiac procedure performed in 3 Danish regions from 2000-2020. The registry included 282,883 new patients entries of which 232,592 was grouped as IHD. Results: Steady increase in number of investigations was observed over 15 years with stabilization of the absolute number of interventions after 2005 with subsequent decrease in treatment fraction. Data demonstrated a comparable regional activity, but significant differences in the incidence of IHD between individual municipalities. Conclusion: The screening, investigation and intervention initiative during the last two decades has proven effective which is demonstrated by the falling incidence of new cardiovascular diseases. However, for further and faster achievements, rapidly growing use of prevention and treatment resources should be allocated to focussed areas by taking in-country differences in consideration.

Value of expert opinion in recommending early intensive lipid lowering in patients with ACS

Opinion is the medium between knowledge and ignorance Plato (427–347 BC) A working group, with representatives from the European Association of Preventive Cardiology and the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy, state in a position paper that a ‘strike early and strong’ approach is needed in patients after acute coronary syndrome (ACS).1 Although this approach seems reasonable, there are no randomized clinical trials (RCTs) demonstrating that the approach improves clinical outcomes. The authors use six lines of reasoning to support their recommendations. First, lower LDL-C is better. Second, getting the LDL-C to goals is critical. Third, recurrent ischaemic events occur early and before the time that step-wise increase of lipid-lowering therapies is achieved. Fourth, currently, patients are not discharged on optimal lipid-lowering therapy, and there is a lack of therapy changes on follow up when LDL-C goals are not achieved. Fifth, early and strong lipid-lowering therapy decreases plaque size. Sixth, this approach is likely to be safe.

Age and Marital Status Predict Mild Cognitive Impairment During Acute Coronary Syndrome Admission: An Observational Study of Acute Coronary Syndrome Inpatients.

Mild cognitive impairment (MCI) has been reported after acute coronary syndrome (ACS), but it is uncertain who is at risk, particularly during inpatient admission. In this study, we aimed to explore the prevalence and cognitive domains affected in MCI during ACS admission and determine factors that identify patients most at risk of MCI. Inpatients with ACS were consecutively recruited from 2 tertiary hospital cardiac wards and screened with the Montreal Cognitive Assessment and the Hopkins Verbal Learning Test. Screening included health literacy (Newest Vital Sign), depressive symptoms (Patient Health Questionnaire-9), and physical activity (Physical Activity Scale for the Elderly). Factors associated with MCI were determined using logistic regression. Participants (n = 81) had a mean (SD) age of 63.5 (10.9) years, and 82.7% were male. In total, MCI was identified in 52.5%, 42.5% with 1 screen and 10% with both. Individually, the Montreal Cognitive Assessment identified MCI in 48.1%, and the Hopkins Verbal Learning Test identified MCI in 13.8%. In Montreal Cognitive Assessment screening, the cognitive domains in which participants most frequently did not achieve the maximum points available were delayed recall (81.5%), visuospatial executive function (48.1%), and attention (30.9%). Accounting for education, depression, physical activity, and ACS diagnosis, the likelihood of an MCI positive screen increased by 11% per year of age (odds ratio, 1.11; 95% confidence interval, 1.04-1.18) and by 3.6 times for those who are unmarried/unpartnered (odds ratio, 3.61; 95% confidence interval, 1.09-11.89). An estimated half of patients with ACS screen positive for MCI during admission, with single and older patients most at risk. Multiple areas of thinking were affected with potential impact on capacity for learning heart disease management.

145 PREDICTION OF NEW ONSET ATRIAL FIBRILLATION IN PATIENTS WITH ACUTE CORONARY SYNDROME UNDERGOING PERCUTANEOUS CORONARY INTERVENTION USING THE C2HEST AND MC2HEST SCORES A REPORT FROM THE MULTICENTER REALE-ACS REGISTRY

Abstract Aims New onset atrial fibrillation (NOAF) is associated with worse clinical outcomes after acute coronary syndrome (ACS). Identification of patients at risk of NOAF remains challenging, and various clinical scores of varying complexities have been proposed to predict incident AF. We tested the value of the simple C2HEST score for predicting NOAF in patients with ACS. Methods We studied patients from the prospective ongoing multicenter REALE-ACS registry of patients with ACS. NOAF was the primary endpoint of the study. The C2HEST score was calculated as coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age ≥75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). We also tested the mC2HEST score. Results We enrolled 555 patients (mean age 65.6±13.3 years; 22.9% women), of which 45 (8.1%) developed NOAF. Patients with NOAF were older (p&amp;lt;0.001) and had more prevalent hypertension (p=0.012), COPD (p&amp;lt;0.001) and hyperthyroidism (p=0.018). Patients with NOAF were more frequently admitted with STEMI (p&amp;lt;0.001), cardiogenic shock (p=0.008), Killip class ≥2 (p&amp;lt;0.001) and had higher mean GRACE score (p&amp;lt;0.001). Patients with NOAF had a higher C2HEST score compared with those without (4.2±1.7 vs 3.0±1.5, p&amp;lt;0.001). A C2HEST score &amp;gt;3 was associated with NOAF occurrence (odds ratio 4.33, 95% confidence interval 2.19-8.59, p&amp;lt;0.001). ROC curve analysis showed good accuracy of the C2HEST score (AUC 0.71, 95%CI 0.67-0.74) and mC2HEST score in predicting NOAF (AUC 0.69, 95%CI 065-0.73). Conclusion The simple C2HEST score may be a useful tool to identify patients at higher risk of developing NOAF after presentation with ACS.

1067 TELEMEDICINE FOR LIPID LEVELS FOLLOW UP AFTER ACUTE CORONARY SYNDROME

Abstract Background The implementation of guidelines on LDL cholesterol levels after acute coronary syndrome (ACS) is very poor according to registries and surveys. Telemedicine could improve adherence to guidelines and facilitate clinical follow-up of patients with ACS, even with the limitations of Covid-19 pandemic. Aim of the study To evaluate the efficacy of telemedicine follow-up in improving adherence to LDL guidelines and improving rates of prescription of PCSK9-inhibitors. Design and Methods 650 consecutive patients discharged with diagnosis of ACS or Chronic CS were enrolled in the study and followed after 2 and 4 months. LDL levels and lipid lowering drug prescription were recorded. Data from 300 patients with ACS patients and &amp;lt;80 years were analyzed and LDL values of telemedicine followed-up patients (telephone/smartphone app/pc teleconsultation) were compared with controls. Results Baseline mean LDL levels were 120 mg/dl, 55% of patients were naive of lipid lowering therapy. At second follow-up mean LDL levels were 55 mg/dl (p&amp;lt;0.05 vs baseline) and rates of prescription of statins, ezetimibe and PCSK9-inhibitors were 98%, 79%, and 18% respectively. Rates of subjects with LDL levels below recommended threshold were 4% at baseline, 39% at first follow-up, 53% at second follow-up (p&amp;lt;0.05). Patients followed up with telemedicine showed lower LDL levels at second follow-up (55vs72 mg/dl, p=0.08) and higher rates of subjects below recommended LDL levels (63%vs30%, p=0.05). Conclusions Telemedicine follow-up may improve the implementation of guideline recommended LDL levels after ACS.

Comparative Effectiveness of Ticagrelor, Prasugrel, and Clopidogrel for Secondary Prophylaxis in Acute Coronary Syndrome: A Propensity Score-Matched Cohort Study.

Comparative effectiveness evaluation of newer P2Y12 inhibitors (prasugrel and ticagrelor) compared with clopidogrel after acute coronary syndrome (ACS) is limited in real-world US populations. The objective of this study was to evaluate cardiovascular events based on ticagrelor, prasugrel, and clopidogrel use in a real-world patient setting. This retrospective cohort study used the IBM MarketScan database (January 1, 2013, to December 31, 2018) to create three propensity score-matched pairs: ticagrelor vs. clopidogrel (N= 21,719), prasugrel vs. clopidogrel (N= 11,513), and prasugrel vs. ticagrelor (N= 11,065). The primary outcome was a composite of myocardial ischemia, unstable angina, stroke, and heart failure hospitalization. These groups were compared in a time-to-event analysis for the primary outcome at 30, 90, and 180 days following P2Y12 inhibitors initiation after percutaneous coronary intervention. Compared with clopidogrel, ticagrelor use suggested a 10% reduction in the primary outcome at 90 days (hazard ratio (HR): 0.90, 95% confidence interval (CI): 0.82-0.99). There were no differences for all other matched pairs or follow-up combinations. In the subgroup analysis of females, the results suggested a risk reduction of 27% for prasugrel at 30 days (HR: 0.73, 95% CI: 0.53-1.00) and 17% for ticagrelor at 90 days (HR: 0.83, 95% CI: 0.70-0.98) when compared with clopidogrel. Among patients treated with bare-metal stents, the results suggested that prasugrel vs. ticagrelor was associated with a 55% and 33% reduced risk for the primary outcome at 30 days and 180 days, respectively. With limited evidence in the United States comparing these drugs, this study helps inform clinicians when choosing P2Y12 inhibitors after ACS.

Toward Personalized DAPT: Is There an Inter-Manufacturer Difference in Generic Clopidogrel Response?

To compare rates of clopidogrel response among patients receiving medication produced by 2 different manufacturers after acute coronary syndrome (ACS) and/or percutaneous coronary intervention. This quality-improvement project included 515 adult patients receiving clopidogrel for ACS or ischemic heart disease and referred for coronary angiography/ percutaneous coronary intervention. The project was divided into 2 phases: (1) retrospective collection of baseline data (April 2019-October 2020); and (2) two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time (November 2020-May 2021). The primary outcome was clopidogrel response measured by platelet function testing, defined as adenosine diphosphate (ADP) response <40% on light transmission aggregometry. Of 515 total patients included in both phases (mean age, 64.5 ± 11.4 years; 351 men [68.2%]; 450 with ACS [87.4%]), 52% were found to be clopidogrel responders based on results of platelet function testing. Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared with the Manufacturer 2 group (34.8% vs 55.1%, respectively; P=.03). After adjustment for age, sex, body mass index, aspirin response, therapeutic hypothermia, left heart catheterization indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (odds ratio 0.96; 95% confidence interval, 0.95-0.97; P<.001) and manufacturer (odds ratio, 2.45; 95% confidence interval, 1.18-5.22; P=.02) were associated with clopidogrel response. In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability.

Kardiologische Rehabilitation

A scientific guideline has been developed to update and harmonize exercise based cardiac rehabilitation (CR) in German speaking countries of Europe. It addresses all aspects of CR including indications, contents and delivery. Four meta-analyses were performed to evaluate the prognostic effect of CR after acute coronary syndrome (ACS), after coronary bypass grafting (CABG), in patients with systolic heart failure (HFrEF), and to define the effect of psychological interventions during CR. Other indications for CR were based on a predefined semi-structured literature search and recommendations were established by a formal consenting process. CR is associated with a significant reduction in all-cause mortality in patients after ACS and CABG, whereas HFrEF-patients benefit in terms of exercise capacity and health-related quality of life. Patients with other cardiovascular diseases such as heart valve surgery or intervention, adults with congenital heart disease and peripheral arterial disease also benefit from CR-participation, but the scientific evidence is less clear. There is increasing evidence that the beneficial effect of CR strongly depends on "treatment intensity" including medical supervision, modulation of cardiovascular risk factors, information and education, and a minimum of individually adapted exercise volume. Additional psychologic interventions (PI) should be performed on the basis of individual needs. There was a trend towards reduction of depressive symptoms for "distress management" and "lifestyle changes" for PI. Patient education is able to increase patients` knowledge and motivation as well as behavior changes regarding physical activity, dietary habits and smoking cessation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. This guideline reinforces the substantial benefit of CR in specific cardiac indications, and it points out the minimal therapeutic needs in CR-delivery.

Long-term dual antiplatelet therapy and nuisance bleeding: impact on quality of life.

Long term dual antiplatelet therapy (LTDAPT), with ticagrelor 60 mg and low-dose aspirin, is indicated after acute coronary syndrome (ACS) for the secondary prevention of atherothrombotic events in high-risk patients with a history of ACS of at least 1 year. LTDAPT had a good tolerability and safety profile, but the risk of TIMI major bleeding was increased. However, even non-significant bleeding may be important because it has an effect on the quality of life and therefore may lead to treatment discontinuation. We, therefore, evaluated patients' experiences with LTDAPT and the impact of nuisance bleeding on quality of life and treatment adherence. We retrospectively reviewed 225 patients in follow-up after ACS with at least one high-risk condition, treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The outpatient follow-up program after hospitalization provides a visit on day 30 after discharge, then after 3 months, continuing with six-monthly checks. We assessed the presence and intensity of bleeding, as well as health-related quality of life (HRQoL), at each visit. The TIMI score was used to determine the severity of the bleeding. Any overt bleeding event that did not meet the major and minor criteria was labeled "minimal" and could be framed as "nuisance bleeding." The HRQoL was assessed by the EuroQol-5 and Dimension (EQ-5D) visual analog scale (VAS) score. Minimal bleedings were present in 49 patients (21%), but only in one case (by decision of the patient) there was a cause for discontinuation of therapy. However, 39 (79%) subjects had asked for opinions on stopping the therapy during the telephone consultation. Factors influencing LTDAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from the hospital. All adverse events, judged to be "not serious" in trials, may have an effect on the quality of life and therefore may lead to treatment discontinuation. The authors underline the importance of careful outpatient follow-up and ongoing counselling, to check out compliance and possible adverse effect of LTDAPT.

Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

BackgroundPleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status.MethodsBiochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension.ResultsClinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM.ConclusionsOur preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.

Abstract 12866: Risk Factors For Major Adverse Cardiovascular Events Post-Acute Coronary Syndrome Hospitalization in Patients With Myeloproliferative Neoplasms

Introduction: Myeloproliferative neoplasms (MPNs) are clonal stem cell neoplasms associated with increased thrombotic risk. However, long-term outcomes after acute coronary syndrome (ACS) and identification of MPN-specific risk factors have not been characterized. Methods: Single-center, retrospective cohort of patients with MPN admitted for ACS from 2000 to 2020 (n = 41). Primary outcomes were major adverse cardiac events (MACE) and bleeding. MACE was composite of cardiovascular (CV) death, myocardial infarction, ischemic stroke, and heart failure (HF) hospitalization. Patients with and without MACE and bleeding were compared to identify risk factors; univariable and multivariable Cox proportional hazards and competing-risk regression models were used. Results: Patient characteristics described in Table 1. After a median follow-up of 80 months, 28 patients had MACE and 14 experienced bleeding. Patients with MACE had shorter median time to index ACS event (35 mos vs 76) and higher rates of JAK2 mutation (82% vs 54%), history of HF (46% vs 15%), and median white blood cell count (WBC, 13 vs 8) at index event compared with patients without MACE. Patients with bleeding had higher rates of JAK2 mutation (93% vs 63%) and WBC (17 vs 10), and lower hydroxyurea use (50% vs 85%) compared with patients without bleeding. Cox and competing-risk regression results in Table 2. Conclusions: Patients with MPN and ACS are at high risk of MACE and bleeding. JAK2 mutation and elevated WBC count (≥ 20 K/μL) at time of index ACS were associated with MACE and bleeding. ACS event occurring within 12 months of MPN diagnosis was associated with MACE. Larger studies are needed to confirm our results.

Abstract 10470: Projected Lifetime Benefits of Alirocumab in Patients After Acute Coronary Syndrome

Introduction: In the ODYSSEY OUTCOMES trial, alirocumab improved cardiovascular outcomes and reduced death after acute coronary syndrome (ACS). Median follow-up was 2.8 yrs (range 2-5). The effects of alirocumab on long-term survival are unknown. Objective: To calculate projected life span and potential survival gains with alirocumab vs placebo after ACS using validated nonparametric age-based methods. Methods: In ODYSSEY OUTCOMES (NCT01663402), 18,924 patients with recent ACS and elevated atherogenic lipoproteins despite high-intensity or maximum-tolerated statin therapy were randomized to alirocumab or placebo. All-cause death was a secondary trial outcome. Age-based estimates of projected survival and event-free (all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke) survival were calculated. In each treatment arm at every year of age, lifespan was estimated from area under the survival curve, to a maximum of 85 yrs. Differences in areas under the survival curves provide an estimate of the benefit of alirocumab on survival. Results: Mean (SD) baseline age was 58.5 (9.3) yrs. Mean survival benefits with alirocumab vs placebo ranged from 0.03 to 1.62 yrs, decreasing with age and becoming neutral at age 80-85 yrs. For example, at age 40, estimated survival was another 37.5 yrs with alirocumab and 35.9 yrs with placebo (difference 1.62 yrs [95% CI, 0.30-2.94]; P =0.016). At age 60, it was 20.5 vs 19.6 yrs (difference 0.88 [95% CI, 0.16-1.61]; P =0.017); at age 75 it was 8.8 vs 8.3 (difference 0.57 [0.09-1.05]; P =0.019); and at age 80, it was 4.5 vs 4.5 years (difference 0.03 [-0.28 to 0.35]; P =0.83). Mean event-free survival benefit similarly ranged from 1.85 to 0.0 yrs. Conclusions: Modeling suggests that long-term treatment with alirocumab may result in a meaningful increase in survival among patients less than 80 yrs of age. This analysis may facilitate shared decision-making with patients. Funding: Sanofi, Regeneron Pharmaceuticals

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry

BackgroundPrevious studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. Methods and resultsCORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39–0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5–2.39 and HR 1.85,95%CI 1.6–2.14, respectively). ConclusionsIncidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.

Long-term mortality after acute coronary syndromes among patients with normal, mildly reduced, or reduced ejection fraction.

Left ventricular ejection fraction (LVEF)≤40% is a well-established risk factor for mortality after acute coronary syndromes (ACS). However, the long-term prognostic impact of mildly reduced ejection fraction (EF) (LVEF 41-49%) after ACS remains less clear. This was a retrospective study enrolling patients admitted with ACS included in a single-centre databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF≥50%), mildly reduced (LVEF 41-49%), and reduced (LVEF≤40%). The endpoint of interest was all-cause death after hospital discharge. A multivariable Cox model was used to adjust for confounders. A total of 3200 patients were included (1952 with normal EF, 375 with mildly reduced EF, and 873 with reduced EF). The estimated cumulative incidence rates of mortality at 10years for patients with normal, mildly reduced, and reduced EF were 24.8%, 33.5%, and 41.3%, respectively. After adjustments, the presence of reduced EF was associated with higher mortality compared with normal EF [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.36-1.96; P<0.001], as was mildly reduced EF compared with normal EF (adjusted HR 1.33; 95% CI 1.05-1.68; P=0.019). The presence of reduced EF was not associated with a statistically significantly higher mortality compared with mildly reduced EF (adjusted HR 1.23; 95% CI 0.96-1.57; P=0.095). In patients with ACS, mildly reduced EF measured in the acute phase was associated with higher long-term mortality compared with patients with normal EF. These data emphasize the importance of anti-remodelling therapies for ACS patients who have LVEF in the mildly reduced range.

Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome

Studies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population. To evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS). This is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022. The outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses. Of 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change. Among stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population. ClinicalTrials.gov Identifier: NCT00202878.

Independent association of PCSK9 with platelet reactivity in subjects without statin or antiplatelet agents.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could predict cardiovascular event in patients with well-controlled LDL-C levels, suggesting an LDL-independent mechanism of PCSK9 on the cardiovascular system. Accumulating evidence suggests PCSK9 might be associated with increased platelet reactivity. This study aimed to assess the relationship between PCSK9 levels and platelet reactivity in subjects not taking statins or antiplatelet agents. A cross-sectional study was conducted to investigate the independent contribution of PCSK9 to platelet activity by controlling for the potential confounding factors. The study population included 89 subjects from a health examination centre who underwent routine annual health check-ups or had an examination before a selective operation. Subjects taking statins or antiplatelet agents were excluded. Adenosine diphosphate (ADP)-induced platelet aggregation was determined by PL-11 platelet analyzer using impedance aggregometry and plasma PCSK9 levels were determined using an ELISA. Serum Lipid profile was assessed by measuring the concentration of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), with low-density lipoprotein cholesterol (LDL-C) being directly measured using enzymatic techniques. The association between PCSK9 and platelet reactivity was investigated. The study subjects were composed of 53 males and 36 females with an average age of 55 (±11) years old. The univariate correlation analysis showed significant correlation between ADP-induced maximal aggregation rate (MAR) and PCSK9 (r = 0.55, p < 0.001) as well as TC (r = 0.23, p = 0.028), LDL-C (r = 0.27, p < 0.001), and PLT (r = 0.31, p = 0.005). Being male (41.2% vs. 46.6, p = 0.04) and smoking (37.4 vs. 46.2%, p = 0.016) were associated with lower ADP-induced MAR than being female and non-smoking. However, there is no correlation between PCSK9 and AA-induced platelet maximal aggregation rate (r = 0.17, p = 0.12). Multiple regression analysis suggested that PCSK9 contributed independently to ADP-induced maximal aggregation rate (β = 0.08, p = 0.004) after controlling for the effect of TC, LDL-C, PLT, being male, and smoking. PCSK9 is positively associated with platelet reactivity, which may partly account for the beneficial effect of PCSK9 inhibition in reducing the risk of major adverse cardiovascular events after acute coronary syndrome (ACS).