Composite Of Major Adverse Cardiovascular Events Research Articles

The triglyceride-glucose index might be a better indicator for predicting poor cardiovascular outcomes in chronic coronary syndrome

Abstract Background Abnormal glucose, and lipid metabolism all play major roles in the process of atherogenesis and are thus substantial risk factors for the development of coronary artery disease. Purpose We sought to investigate whether the triglyceride-glucose index (TyG) and the Atherogenic Index of Plasma (AIP), surrogates for atherosclerosis, are linked to major adverse cardiovascular events (MACE) in patients with Chronic Coronary Syndrome (CCS). Methods and Results Seven hundred ten-five consecutive patients with intermediate risk for CCS who presented to the outpatient clinic between June 2020 and August 2022 were included retrospectively. MACE included non-fatal myocardial infarction, heart failure, cerebrovascular events, non-cardiac mortality, and cardiac mortality. The composite of MACE was determined to be the primary outcome at follow-up after discharge. Secondary outcomes were defined as each individual parameter of MACE. For the primary outcome's time-to-event analysis, the Kaplan-Meier plots, and Cox proportional hazard models were done.The overall population’s median age was 55 years, with males accounting for 58%. The median follow-up time was 17 months. On multivariate cox regression analysis, age, hypertension, Coronary Artery Disease-Reporting and Data System score, and TyG index were found to be independent predictors of the primary outcome. The primary outcome rate was higher in individuals with high TyG than in those with low TyG (18.7% vs 3.8%, p<0.001). Likewise, patients with high TyG had statistically higher rates of cerebrovascular events, heart failure, non-fatal MI, non-cardiac mortality, and cardiac mortality than the latter. Conclusion We found that the TyG might predict poor cardiovascular outcomes in CCS patients.Table 1Figure 1

Relationship of clinical complexity domains to management and outcomes of european and asian patients with atrial fibrillation: a comparison of two regional prospective observational AF registries

Abstract Background Clinical complexity domains, defined as multimorbidity, frailty and polypharmacy, have been associated with worse clinical outcomes in atrial fibrillation (AF) patients. Differences between European and Asian patients in the prevalence of these clinical complexity domains, the differential prescription of oral anticoagulant (OAC) and risks of clinical outcomes remain unclear. Purpose To examine the epidemiology and impact of clinical complexity domains in a large prospective cohort of European and Asian AF patients on OAC prescriptions and the risk of clinical outcomes. Methods We studied AF patients derived from two large prospective observational AF registries, conducted in Europe and Asia, on the basis of the same electronic case report form. Multimorbidity and polypharmacy were defined according to the number of comorbidities and drugs at baseline, while frailty was defined according to a 40-items frailty index (FI). Prescription of OAC was assessed at baseline. The primary clinical outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Logistic and Cox regression analyses were used to determine associations with domains, and interaction analyses were performed to investigate differences between European and Asian patients. Results European patients had a higher burden of all three clinical complexity domains (Multimorbidity: 79.5% European vs 70.2% Asian, p<0.001; Frailty: 21.3% European vs 7.8% Asian, p<0.001; Polypharmacy: 53.9% European vs 36.7% Asian, p<0.001). At baseline, Asian patients with multimorbidity, frailty and polypharmacy were less likely prescribed with OAC than European ones, with the largest difference seen in frail patients (83.0% European vs 76.2% Asian, p=0.003). After adjustments, being frail was associated with lower OAC prescription (OR 0.45, 95% CI 0.39-0.52), while Asian patients were less likely prescribed OAC than Europeans (OR 0.34, 95% CI 0.25-0.45 vs. OR 0.47, 95% CI 0.40-0.55, Pint=0.037). Adjusted Cox regression found that in the overall population, clinical complexity domains were associated with a higher risk of composite outcome, all-cause death, and MACEs [Figure 1]. On subgroup analysis, frail Asian patients had a higher risk of composite outcome (Pint= 0.003) compared with Europeans [Figure 1]. Similarly, a higher risk of all-cause death was found among Asians [Figure 1] for all the three clinical complexity domains [Figure 1]. Conclusions Clinical complexity domains have different epidemiological characteristics amongst European and Asian AF patients, being more prevalent in Europeans. These domains differently affect European and Asian patients in terms of OAC use. The presence of clinical complexity domains increases the risk of several clinical outcomes, with Asian patients being burdened with a much higher risk compared to Europeans.Figure 1

Carotid plaque score for stroke and cardiovascular risk prediction in a middle-aged cohort from the general population: the akershus cardiac examination 1950 study

Abstract Background Assessment of carotid atherosclerosis with ultrasound may have an unfilled potential in predicting stroke and cardiovascular events. Purpose We aimed to explore the predictive value of the carotid plaque score compared to the Systematic COronary Risk Evaluation (SCORE) 2 risk prediction algorithm, on incident stroke and major adverse cardiovascular events (MACE), and establish a prognostic cut-off for the carotid plaque score. Methods In the prospective Akershus Cardiac Eexamination (ACE) 1950 cohort study, carotid plaque score was calculated with ultrasound at inclusion in 2012-2015. The largest plaque diameter in each extra cranial segment of the carotid artery both sides was measured and scored from 0-3 points. The sum of each segment provided the carotid plaque score. Incident stroke and composite endpoint MACE (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) was assessed by linkage to national registries throughout 2020. Results Carotid plaque score was available in 3650 (98.5%) of the participants, with mean age at inclusion was 63.9±0.64 years. Only 462 (12.7%) were free of plaque and the median carotid plaque score was 2 (IQR 1-4). By the end of 2020, 42 (1.2%) subjects had experienced a stroke and 145 (4.0%) a MACE. Carotid plaque score was a predictor of incident stroke (HR 1.25, 95%CI 1.15-1.36) and MACE (OR 1.21, 95%CI 1.14-1.27) after adjustment for SCORE2, and outperformed SCORE2 in predicting stroke (p=0.001). The best cut-off value for carotid plaque score determined by receiver operator characteristics area under the curve was ≥4 with a positive predictive value 2.5% and negative predictive value 99.3%. Conclusion Carotid plaque score is a strong predictor of incident stroke and MACE and outperforms SCORE2 for risk prediction in a middle-aged cohort recruited from the general population. A cut-off score of ≥4 seems to be suitable to identify high-risk subjects.Graphical AbstractCarotid plaque score distribution

Association of pulse pressure with risk of major adverse cardiovascular events among cardiovascular outcome trial participants

Abstract Background Hypertension is a well-established risk factor for the development for cardiovascular (CV) disease and accumulating evidence also implicates elevated pulse pressure (PP), a surrogate marker for arterial stiffness, as an independent risk factor for major adverse cardiovascular events (MACE). Purpose The study aimed to assess the association of PP with MACE among participants in multiple CV outcome clinical trials. It also aimed to determine if the presence of various CV comorbidities impacts the association between PP and MACE. Methods Adult patients between the ages of 19-98 years (n = 65,382, mean age 63) enrolled in five large CV outcome trials (ACCELERATE, STRENGTH, PRECISION, ALECARDIO, and LIGHT) with independently adjudicated clinical end points were identified. Baseline demographics, medical history, blood pressures, and CV medications were collected. Univariate and multivariate analyses were generated and analyzed for temporal trends, risk, and adjusted survival. Results Participants had a mean baseline blood pressure of 128 /76 mm Hg and a mean PP of 52 mm Hg. Forty-five percent were women, 31% had coronary artery disease, 51% had type 2 diabetes mellitus, 84% had hypertension, 25% had history of myocardial infarction (MI), and 35% had a history of an acute coronary syndrome. The composite MACE end point included CV death, myocardial infarction, or stroke and occurred in 3712 participants (5.7%).The composite end point of all cause death, myocardial infarction, and stroke occurred in 4513 participants (6.9%). For every 10 mm Hg increase in PP there was an increased risk of MACE (unadjusted hazard ratio (HR) 1.20, 95% CI 1.17 to 1.23). Similarly, a PP > 60 mmHg demonstrated an unadjusted HR of 1.53 (95% CI 1.43 to 1.64) compared with PP < 60 mm Hg. Although increased PP was a risk factor in both men and women, every 10 mm Hg increase in PP was associated with higher risk of MACE in women (adjusted HR 1.17, 95%CI 1.17, 1.12 to 1.22) compared with men (adjusted HR 1.09, 95% CI, 1.05 to 1.12). Table 1 displays the adjusted HR for patients grouped by race, history of prior CV disease, or the presence of CV risk factors (diabetes and chronic kidney disease.) While most subgroups demonstrated an increased risk of MACE with increasing PP, PP was not associated with MACE among individuals with a history of stroke (HR 1.00, 95% CI 0.92 to 1.08). Kaplan-Meier survival curves comparing PP greater than or less than 60 mm Hg are seen in Figure 1. Conclusions Among CV outcome clinical trial participants, with independently adjudicated end points, baseline PP is associated with an increased risk for future MACE. The association stands for most participant subgroups except for participants with a prior history of stroke.Table 1Figure 1

Incidence of major cardiovascular outcomes in patients with chronic kidney disease by severity: a United States population-based study using electronic medical records

Abstract Background and Aims Data on the incidence of cardiovascular (CV) events by stage of chronic kidney disease (CKD) and the effect of previous CV history on future events in CKD patients (pts) is limited. We aimed to analyze a large US electronic medical record (EMR) database and evaluate incidence of new major adverse CV events (MACE) per CKD stage over a 5-year follow-up. Methods A retrospective cohort study was conducted using IBM® Explorys EMR data (>53 million patients) from Jan 2010 to Dec 2019. Two cohorts of CKD patients were created: Cohort 1 based on diagnostic codes (n = 810,987 pts), and Cohort 2 on KDIGO screening/staging criteria (n = 953,396). Sub-cohorts were created for each CKD stage (1-5). CKD classification was not mutually exclusive (individual pts could contribute to multiple main and sub-cohorts). Pts in Cohort 1 were required to have an ICD 9/10 code for a specific CKD stage while pts in Cohort 2 required two consecutives abnormal eGFR, uACR/uPCR results within 3-18 months to determine KDIGO CKD stage. Pts were required to have at least 12-months lookback period. Index date was the date of diagnosis or second abnormal test. We followed up each patient individually until the occurrence of a composite of MACE including death, coronary artery disease (CAD) events, any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. Results Most patients in Cohort 1 (DxC) and 2 (KDIGO) were Caucasian and had stage 3 CKD at baseline. Mean age was 70y and 71y in Cohort 1 and 2 respectively, with 49% and 40% males. The prevalence of pre-existing CV diseases increased with CKD stage. The proportion of pts from Cohort 2 receiving a diagnosis of CKD at least once during their study period increased from 34% in stage 1 to 86% and 83% in stage 4 and 5, respectively. The 5-year incidence of the composite of MACE increased with stage in both cohorts: 40.3% to 66.0% in Cohort 1 and 25.1% to 65.8% in Cohort 2. These incidences were higher in pts with a CV history (Table 1). DxC pts tended to have a higher incidence of MACE, especially in the early stages. Death was the most frequent event at 5y in both cohorts across all stages (27.8% and 19.7% respectively at stage 3). It occurred in half of pts with a prior history of CV disease in both Cohorts in stages 4-5 CKD. Stroke was the most frequent event in the early stages (21.6% and 19.5% respectively at stage 3) and CAD events the most frequent in the late stages (27.6% and 29.5% respectively at stage 5). Conclusion CKD pts have a high risk of MACE at 5 years, with incidence 2-3 times higher in patients with pre-existing CV disease. There are differences in MACE incidences between CKD definitions, that were higher in coded diagnoses vs. lab results, especially in stages 1-3, warranting further investigation. Aggressive treatment of CV disease and risk factors should be considered for all CKD pts due to high 5-year MACE rates, regardless of CKD stage.Table 1.

Abstract 16620: Long-Term Prognostic Factors for Cardiovascular Events in Patients With Chest Pain Without Diabetes Mellitus and Significant Coronary Stenosis

Background: Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD and DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. Methods: A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiovascular events (MACE) were defined as the composite of total death, myocardial infarction (MI), and revascularization. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of MACE, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Results: Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a recurrent chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia, ICS, the use of aspirin and nitrates were associated with long-term MACCE. Conclusions: Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with anti-anginal medications.

Abstract 16244: Oncologic Disease and In-Stent Restenosis: A Nationwide Analysis

Introduction: Recent studies have shown that Ischemic Heart Disease (IHD) is leading cause of cardiovascular mortality in cancer patients. There is little information about In-Stent Restenosis (ISR), one complication of IHD treatment. ISR has been associated with the presence of underlying risk factors but there is no clear association between cancer and ISR. Methods: A retrospective cohort study was made selecting a sample of adult patients using the National Inpatient Sample (NIS) database from January 2017 to December 2019. Patients with cancer were identified and stratified by 5 main sites: lung, breast, gastrointestinal, prostate, and hematological tissue. Main outcome was odds of ISR in the oncologic population. Secondary outcomes were Major Adverse Cardiovascular Events (MACE) and mortality in patients with ISR, stratified by presence or absence of cancer. Univariate and multivariate analysis were done, adjusting for possible confounders. Results: A total of 90,900,000 adults were identified, of which 4,888,734 had cancer. From the adult population, 197350 patients with ISR were identified. Primary analysis revealed that cancer is not associated with increased odds of ISR but rather decreased, adjusted for other comorbidities, with an OR=0.181(IC95%=0.167-0.198, p=0.001). Paradoxically, secondary analysis of the ISR subpopulation showed statistically significant differences between cancer and non-cancer patients in the rate of composite MACE, and other cardiovascular outcomes such as Heart Failure, Atrial Fibrillation, and other arrhythmias (Table 1). Conclusions: The present study shows that cancer is associated with decreased odds for ISR, but in with patients with ISR cancer was associated with higher prevalence of composite MACE, mainly due to arrhythmias and heart failure. Further studies are needed to explain the dynamic relationship between cancer and endothelial dysfunction.

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases

Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

Effect of Lipid-Lowering Drugs on Renal and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Dyslipidemia: ARetrospective Cohort Study.

The effects of lipid-lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end-stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non-LLD users; the final follow-up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub-distribution hazard regression models adjusted for multivariables, including time-varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65-0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62-0.93) than did non-LLD users. After adjusting for time-varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65-0.93) and MACEs (aHR, 0.77, 95% CI, 0.60-0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non-LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects.

Elevated triglyceride levels are associated with increased risk for major adverse cardiovascular events in statin-naïve rheumatoid arthritis patients: A nationwide cohort study

ObjectivesTo investigate the association between the four components of the lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) at baseline and composite major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events. MethodsThis nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. ResultsDuring follow-up (median 4.70 years), the incidence of MACE per 1000 person-years was 7.27. Among the four lipid components, only higher baseline TG levels were significantly associated with increased risk for composite MACE in RA subjects. The risk for composite MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.35 [95% confidence interval (CI), 1.03–1.78]) and highest quartiles (adjusted HR, 1.74 [95%CI, 1.33–2.28]) of baseline TG level versus the lowest quartile. ConclusionsIn statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population.

Updates in Small Interfering RNA for the Treatment of Dyslipidemias.

Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the well-known association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use of RNA-based therapies can help the treatment of difficult to target lipid disorders. The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10, and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.

Acute kidney injury in hospitalized adults with chronic kidney disease: comparing cROCK, KDIGO, and combined criteria.

Acute-on-chronic kidney disease (ACKD) increases the risk of progression of chronic kidney disease (CKD). This study aimed to evaluate the ability of a novel criteria of reference change value of the serum creatinine optimized criteria for acute kidney injury in CKD (cROCK) to detect ACKD patients. This was a retrospective observational study with a 3-year follow-up. All included patients with CKD stage 3 were evaluated using cROCK, Kidney Disease Improving Global Outcomes (KDIGO), and their combined criteria. The renal composite endpoints, major adverse cardiovascular events (MACEs), and all-cause mortality were recorded as clinical outcomes. A total of 812 patients was enrolled. The cROCK criteria detected more ACKD events than did the KDIGO (68.0% vs. 59.5%, p < 0.001). Compared to KDIGO (-) & cROCK (-) group, ACKD patients diagnosed by cROCK had significantly higher hazard ratio [HR] for renal composite endpoints (HR, 3.591; p < 0.001), MACEs (HR, 1.748; p < 0.001), and all-cause mortality (HR, 2.985; p < 0.001). The patients in KDIGO (+) & cROCK (+) group had the lowest survival probability when considering renal composite endpoints, MACEs, and all-cause mortality (all p < 0.001). Furthermore, cROCK resulted in the largest area under the receiver operating characteristic curve (AUC) for predicting renal composite endpoints, and the combined criteria led to the largest AUC for predicting MACEs and allcause mortality. Compared to the KDIGO, the cROCK detected more ACKD events. Combining both cROCK and KDIGO criteria might improve the predictive ability for long-term outcomes in ACKD patients.

Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiovascular Risk Management in Patients With Type 2 Diabetes Mellitus: A Systematic Review.

People with type 2 diabetes mellitus have a greater risk of developing cardiovascular problems. Since cardiovascular diseases are a major cause of mortality all over the world, we need to findmore efficient measures to control this risk in the diabetes population in addition to conventional glycemic control. In this systematic review, we aim to explore the latest findings on the cardiovascular effects of glucagon-like peptide-1 (GLP-1) agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists in patients with type 2 diabetes mellitus. We conducted a comprehensive literature search using PubMed and Google Scholar as the main sources for data collection. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations for conducting this review. The outcomes of interest included mortality due to cardiovascular causes, non-fatal myocardial infarction, stroke, effects on cardiovascular risk factors, heart failure, and development of arrhythmias. After thorough literature screening and quality analysis, 14 articles were finally included for qualitative synthesis.GLP-1 receptor agonists appeared to be effective in reducing the risk ofcardiovascular mortality, myocardial infarction, and stroke. They were found to reduce the risk of composite major adverse cardiovascular event (MACE) outcomes by 12-14% when compared to placebo. Their role in preventing heart failure and arrhythmias is uncertain, and further trials are needed to confirm the same. The cardiovascular outcomes of GLP-1/GIP dual agonists are currently under investigation.Studies completed to date show that they do not increase the risk of cardiovascular disease when compared to placebo.

Utility of residual SYNTAX score to predict clinical outcome after acute myocardial infarction

Abstract Aims Acute myocardial infarction (AMI) represents a huge health burden and a growing economical challenge, particularly with recurrent major adverse cardiovascular events (MACE). Large attention is critically mandated to identify population at higher risk for recurrent MACE to maximize secondary preventive measures. This study aimed to evaluate the utility of residual SYNTAX Score (RSS) after percutaneous coronary intervention (PCI) to the culprit vessel(s) in patients with AMI (STEMI or NSTEMI) to predict 6-months clinical outcomes. Methods and results A total of 492 eligible AMI patients were recruited through a period of 12 months. The RSS was systematically calculated after the PCI procedures. Median RSS was 4 (minimum 0–maximum 47.5). RSS showed excellent association to mid-term clinical outcomes. At cut-off value of RSS 3 had robust prediction for subsequent heart failure (HF), recurrent AMI, unplanned revascularization and the composite of MACE (P < 0.001). A significantly higher RSS was found in those who developed heart failure through the 6-months follow up period compared to those who did not (10 vs. 3, P < 0.001). Similar significant difference was found for recurrent ACS (11.5 vs. 3, P < 0.001), unplanned revascularization (15 vs. 3, P < 0.001) and occurrence of MACE (12 vs. 3, P < 0.001). Conclusions RSS is a sensitive predictor for 6-months adverse clinical outcomes after AMI. Calculating RSS at the end of PCI can guide intensification of secondary preventive measures. Ability of RSS- tailored management to impact clinical outcomes in high-risk patients is to be evaluated.Improvement, with subsequent amelioration of LV diastolic function. The Dapa group had a significantly greater improvement in LVEF at four months and six months compared to the Empa group. While the Empa group showed a significant improvement in HbA1C at six months compared to the Dapa group. Additional Content An author video to accompany this abstract is available on https://academic.oup.com/eurheartjsupp. Please click on the arrow next to ‘More Content’ and then click on ‘Author videos’.

Hydroxychloroquine use is associated with reduced mortality risk in older adults with rheumatoid arthritis.

There is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE). In a retrospective cohort of Medicare beneficiaries aged ≥ 65years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users. The study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78). HCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.

A marginal structural model to estimate the effect of antidepressant medication treatment on major cardiovascular events among people with post-traumatic stress disorder.

Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model. We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose-response relationship. People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18-1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08-1.44) and TCAs (HR 1.33, 95% CI 1.13-1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE. In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose-response fashion.

Outcomes Following Radiofrequency Renal Denervation According to Antihypertensive Medications: Subgroup Analysis of the Global SYMPLICITY Registry DEFINE.

The Global SYMPLICITY Registry DEFINE (Denervation Findings in Real World) investigates radiofrequency renal denervation (RDN) in a broad range of patients with hypertension. We evaluated whether the number or type of antihypertensive medications were associated with increased long-term blood pressure (BP) reductions and cardiovascular outcomes following radiofrequency RDN. Patients underwent radiofrequency RDN and were categorized by baseline number (0-3 and ≥4) and different combinations of medication classes. BP changes were compared between groups through 36 months. Individual and composite major adverse cardiovascular events were analyzed. Of 2746 evaluable patients, 18% were prescribed 0 to 3 and 82% prescribed ≥4 classes. At 36 months, office systolic BP significantly decreased (P<0.0001) by -19.0±28.3 and -16.2±28.6 mm Hg in the 0 to 3 and ≥4 class groups, respectively. Twenty-four-hour mean systolic BP significantly decreased (P<0.0001) by -10.7±19.7 and -8.9±20.5 mm Hg, respectively. BP reduction was similar between the medication subgroups. Antihypertensive medication classes decreased from 4.6±1.4 to 4.3±1.5 (P<0.0001). Most decreased (31%) or had no changes (47%) to the number of medications, while 22% increased. The number of baseline antihypertensive medication classes was inversely related to the change in prescribed classes at 36 months (P<0.001). Cardiovascular event rates were generally low. More patients in the ≥4 compared with 0 to 3 medication classes had myocardial infarction at 36 months (2.8% versus 0.3%; P=0.009). Radiofrequency RDN reduced BP safely through 36 months, independent of the number and type of baseline antihypertensive medication classes. More patients decreased than increased their number of medications. Radiofrequency RDN is a safe and effective adjunctive therapy regardless of antihypertensive medication regimen. URL: https://www. gov; Unique identifier: NCT01534299.

Time-dependent changes in P2Y12 reaction unit values for predicting the different types of cardiovascular events in patients with ischemic heart disease.

Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.

#3676 EVALUATION OF HAEMOGLOBIN RESPONSE IN PATIENTS WITH CKD-RELATED ANAEMIA NOT ON DIALYSIS RECEIVING DAPRODUSTAT OR CONTROL IN ASCEND-ND

Abstract Background and Aims Daprodustat (Dapro) is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor being investigated in anaemia of chronic kidney disease (CKD). ASCEND-ND1 achieved non-inferiority (NI) for Dapro vs darbepoetin alfa (Darbe) in both coprimary endpoints, mean change in haemoglobin (Hb) levels from baseline to the evaluation period (EP; Week [Wk] 28–Wk 52) and first occurrence of a composite major adverse cardiovascular event, in patients (pts) with anaemia of CKD not on dialysis. Here, we present key Hb efficacy data and evaluate differences in Hb response within ASCEND-ND subgroups. Method Pts with Stages 3–5 CKD (not on erythropoiesis stimulating agents [ESAs]: Hb 8–10g/dL; on ESAs: Hb 8–11g/dL) were randomised 1:1 to Dapro or Darbe. Statistical analysis methods for the coprimary endpoint have been published.1 Secondary endpoints evaluated during the EP included: 1) the percentage of Hb responders (pts with mean evaluable Hb within the analysis range [10–11.5g/dL]); 2) the percentage of time Hb was within the analysis range; 3) analysis of Hb change from baseline to Wk 52. Secondary endpoints were analysed as follows: 1) Cochran-Mantel-Haenszel test adjusted for ESA use and region; 2) Rosendaal method (evaluable Hb values) and Hodges-Lehmann and stratified Mann-Whitney estimates of treatment effect, analysed with a van Elteren's test stratified by ESA use and region; 3) mixed model repeated measures analysis (on-/off-treatment, observed Hb values from Wks 28–52) with factors for ESA use, region, baseline Hb (by time), treatment by time interactions. Secondary and subgroup analyses were not multiplicity adjusted. Results Of 3872 pts in ASCEND-ND (Dapro n = 1937; Darbe n = 1935), mean baseline Hb levels were similar for both treatment arms and mean change in the EP Hb level for Dapro and Darbe met the prespecified NI margin of ‒0.75 g/dL (difference = 0.08g/dL; 95% confidence interval [CI] = 0.03, 0.13).1 Subgroup analyses were consistent with coprimary analyses (Table), with little or no heterogeneity between most groups: 7/22 subgroups (ethnicity, high-level race, region, ESA use at randomisation, prior ESA dose group, history of stroke, and hospitalisation 6 months prior to screening) had interaction p values &amp;lt;0.1; however, all subgroups met the NI criterion with between-group differences that were not clinically meaningful. Proportions of pts within the Hb analysis range were higher for Dapro than Darbe in the EP overall and regardless of baseline ESA use and similar for region (Table). The median (interquartile range) percentage of time Hb was in the analysis range during the EP was 70.5% (45.3%–93.2%) for Dapro vs 63.2% (33.7%–88.9%) for Darbe. Dapro was associated with a nominally NI (margin of ‒15%) and significant increase in percentage time in analysis range during the EP (estimate of median difference [95% CI] = 4.57% [2.04%, 7.11%]; one-sided p&amp;lt;0.0001). The estimate (95% CI) for the probability that Dapro had a greater percentage of time Hb within the analysis range than Darbe was 0.55 (0.53, 0.57); the lower boundary of the 95% CI exceeded 0.50, representing equal probability between the two treatment arms. Results by region were similar for Dapro vs Darbe (treatment effect): Asia Pacific = 0.56; Eastern Europe/South Africa = 0.51; Western Europe/Canada/Australia/New Zealand/Israel, 0.58; Latin America, 0.58; USA, 0.55). In mixed-model repeated measures analysis, g/dL Hb change (standard error) at Wk 52 was 0.76 (0.029) with Dapro and 0.73 (0.029) with Darbe (difference [95% CI] = 0.03 [−0.05, 0.11]). Hb efficacy was similar regardless of ESA use (Figure). Conclusion Dapro was effective and NI to Darbe for maintaining Hb in non-dialysis pts with anaemia of CKD, and results of subgroup analyses were consistent with the coprimary analyses. Additionally, Dapro raised and maintained Hb within the analysis range regardless of baseline ESA use or region. These preliminary analyses indicated a nominal NI showcasing greater Hb time in range with Dapro vs Darbe; further analyses will be presented to fully characterise this interaction.

#3704 EU REGION-SPECIFIC CARDIOVASCULAR EVENT DATA FOR DAPRODUSTAT IN ASCEND-D AND ASCEND-ND

Abstract Background and Aims Daprodustat (GSK1278863) is a hypoxia-inducible factor prolyl hydroxylase inhibitor under investigation for the treatment of anaemia of chronic kidney disease. Phase 3 studies in dialysis (ASCEND-D) and non-dialysis (ASCEND-ND) patients demonstrated the non-inferiority of daprodustat vs recombinant human erythropoietin (rhEPO) control (in ASCEND-D) or darbepoetin alfa (ASCEND-ND) control in terms of the mean change in haemoglobin levels between Weeks 28 and 52 versus baseline and the first occurrence of a composite major adverse cardiovascular (CV) event (MACE) [1, 2]. Post-hoc analyses were conducted to evaluate prespecified CV endpoints for patients enrolled in these studies from participating countries in Europe (EU patients) versus elsewhere (non-EU patients). Method Post-hoc time to the first adjudicated MACE (death from any cause, non-fatal myocardial infarction or non-fatal stroke), time to the first adjudicated MACE or thromboembolic event (TEE; deep vein thrombosis, pulmonary embolism or vascular access thrombosis), and time to the first adjudicated MACE or hospitalisation for heart failure (HHF) were analysed for EU (enrolled from Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden and the UK; not all countries participated in both studies) and non-EU (all other participating countries) patients. Hazard ratios (HRs) and associated 95% confidence intervals were calculated to evaluate the likelihood of CV events with daprodustat versus alternative therapy in both studies. HRs for EU and non-EU patients were compared for each endpoint in each study and p-values were calculated to assess the statistical significance of observed differences. Significance was defined at the 10% level (interaction p-value &amp;lt;0.1). Results ASCEND-D included 415 EU patients and 1072 non-EU patients randomised to daprodustat, and 440 EU and 1037 non-EU patients randomised to rhEPO. ASCEND-ND included 410 EU patients and 1527 non-EU patients randomised to daprodustat, and 407 EU and 1528 non-EU patients randomised to darbepoetin alfa. No significant heterogeneity was observed between EU and non-EU patients in terms of the prespecified CV endpoints (p≥0.1979). In ASCEND-D and ASCEND-ND, the results for MACE, MACE+TEE and MACE+HHF for the EU subgroup were consistent with the non-EU subgroup (Table), as well as with the co-primary analysis [1, 2]. Efficacy and additional safety data for EU versus non-EU patients are being explored and will be included in the subsequent presentation. Conclusion Non-inferiority in terms of the first occurrence of MACE was demonstrated for daprodustat versus rhEPO in ASCEND-D and versus darbepoetin alfa in ASCEND-ND.1,2 Results for EU and non-EU patients in the current analysis were consistent with the global outcomes from both studies.