Ischemic Cardiovascular Events Research Articles

Long-term clinical outcomes of drug-coated balloon angioplasty for de novo coronary lesions in patients with diabetes mellitus.

We investigated whether drug-coated balloon (DCB) treatment is effective for all de novo cases of coronary artery disease (CAD) in patients with diabetes mellitus. Furthermore, we also investigated the relationship between the degree of diabetes mellitus and clinical outcomes after DCB treatment. In this study, we included 516 consecutive patients with de novo CAD who were treated with DCB. The patients were divided into the diabetic and non-diabetic groups. Patients with diabetes mellitus were further classified into non-insulin-treated diabetes mellitus (NITDM) and insulin-treated diabetes mellitus (ITDM). The primary endpoints were major adverse cardiovascular ischemic events (MACE) and clinically driven target lesion revascularization (CD-TLR). Within a mean clinical follow-up period of 2.5years, the incidence of MACE among patients with diabetes mellitus (22.1%) was almost twice that of non-diabetic patients (11.9%) with a relative risk of 1.86 (95% CI 1.24-2.79, p = 0.002). The 3-year CD-TLR occurred in 28 patients with diabetes mellitus (10.6%) and 13 non-diabetic patients (5.1%, p = 0.02). ITDM patients had a significantly higher rate of MACE compared with non-diabetic patients with a relative risk of 2.86 (95% CI 1.76-4.63, p = 0.0002). ITDM remained an independent predictor of 3-year MACE with an odd ratio of 1.96 (95% CI 1.00-3.83, p = 0.05). In patients undergoing DCB, the presence of DM was associated with a higher risk of MACE and CD-TLR. Particularly in DCB, treatment was still inadequately effective for ITDM patients.

Association Between Coronary Calcium Detection on Chest Computed Tomography and Ischemic Cardiovascular Events and Mortality in Asymptomatic Chronic Obstructive Pulmonary Disease Patients. Systematic Review of the Literature

IntroductionLiterature suggests that there is a close relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular (CV) disease. The aim of this study was to assess whether the presence of coronary calcium (CC) on chest computed tomography (CT) in asymptomatic COPD patients is associated with an increased risk of CV events and mortality. Material and methodsA systematic review of the literature was performed following PRISMA recommendations. Studies published in the last 20 years in four databases (PubMed, Web of Science, Embase and MEDLINE) were included. ResultsThree hundred fifty articles were identified, eight of them met the selection criteria. The included studies, conducted between 2013 and 2024, were predominantly multicentre cohort studies. The meta-analysis showed that the presence of CC on chest CT of COPD patients is an independent predictor of CV events (hazard ratio 1.44, 95% CI 1.22–1.70) and associated with an increased mortality during the follow-up period (hazard ratio 1.57, 95% CI 1.35–1.83). ConclusionsOur analysis suggests that the identification of CC on chest CT scans of COPD patients may be useful in the early detection and treatment of CV disease in asymptomatic patients. Prospective, multicentre studies confirming our findings are needed to explore the potential impact of early detection and treatment of CV risk in COPD patients.

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis

ObjectivesChronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease...

Routine Functional Testing or Standard Care in High-Risk Patients after Percutaneous Coronary Intervention.

This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.

Abstract 2007: Ischemic And Non-ischemic Cardiovascular Events Differentially Regulate Cross Disease Communication With Cancer

Cancer and cardiovascular disease (CVD) are the top two leading causes of death worldwide, exhibiting cross-disease communication that increases morbidity. Cancer patients are at significantly increased risk for CVD and recent studies by our lab and others indicate that CVDs like myocardial infarction (MI) or heart failure can in turn accelerate tumor growth. We previously showed this occurs through changes in the innate immune system or via tumor-promoting factors secreted from the damaged myocardium, which together have established the nascent field of Reverse CardioOncology. We hypothesized that ischemic and non-ischemic CVD injuries have distinctly different mechanisms underlying mammary tumor growth. To mimic these events, we modeled non-cardiac hind limb ischemic injury by femoral artery ligation (FAL) and non-ischemic cardiac injury by cardiac cryoinjury (CCI). To test our hypothesis, we introduced primary E0771 mouse mammary cancer cells into the mammary fat pad three days prior to FAL or CCI. Measurements of tumor over time showed significant increases in tumor growth after both FAL and CCI when compared to sham surgeries. However, only the ischemic injury, FAL, induced similar changes in immune cells to what we observed after MI (induced by left anterior descending coronary artery [LAD] ligation). This included significant increases in myeloid populations and decreased lymphocytes within the circulation. Additionally, flow cytometry of immune cells within tumors of mice exposed to FAL showed significantly increased myeloid cells and macrophages, as well as increased immunosuppressive T-regulatory cells. In contrast, while CCI showed significantly increased tumor burden and circulating leukocytes, there were no differences in the above-mentioned subsets of immune cells within the circulation or within the tumor. These data suggest that ischemic injury, via FAL or LAD, induces an immunosuppressive environment within the tumor that accelerates cancer growth that is distinct from the non-ischemic cardiac injury induced by CCI. Taken together, our data suggest that the immune reprogramming after ischemic CVDs is a risk factor for tumor growth and these data help to elucidate the mechanisms that underlie cancer risk in CVD patients.

Clinical Impact of the Use of Warfarin in Patients with Atrial Fibrillation Undergoing Maintenance Hemodialysis.

Background: We evaluated the impact of warfarin use on the clinical outcomes of patients with atrial fibrillation who were undergoing hemodialysis (HD). Methods: A retrospective analysis was conducted utilizing data from patients undergoing maintenance HD who participated in HD quality assessment programs. Patients who were assigned the diagnostic code for atrial fibrillation (n = 4829) were included and divided into two groups based on the use of warfarin: No group (no warfarin prescriptions (n = 4009)), and Warfarin group (warfarin prescriptions (n = 820)). Results: Cox regression analyses revealed that the hazard ratio for all-cause mortality in the Warfarin group was 1.15 (p = 0.005) in univariate analysis and 1.11 (p = 0.047) in multivariable analysis compared to that of the No group. Hemorrhagic stroke was significantly associated with warfarin use, but no significant association between the use of warfarin and ischemic stroke or cardiovascular events was observed. The subgroup results demonstrated similar trends. Conclusions: Warfarin use is associated with a higher risk of all-cause mortality and hemorrhagic stroke, and has a neutral effect on ischemic stroke and cardiovascular events in patients with atrial fibrillation who are undergoing HD, compared to those who are not using warfarin.

Safety of the PCSK9 inhibitor alirocumab: insights from 47296 patient-years of observation.

The ODYSSEY OUTCOMES trial, comprising over 47000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Review and targeted lipidomic biomarkers in atherosclerosis

Ischemic cardiovascular events (ischemic stroke, myocardial infarction) are the most common complications of cardiovascular diseases. One of the leading mechanisms of these complications is atherosclerosis. Lipids play an important role in plaque development. Recently, the lipidome has been of greatest interest, since it may have a prognostic value in atherosclerosis development. With an increase in the circulation of proatherogenic lipidomic biomarkers, the risk of atheroscle­rosis destabilization and ischemic complications increases.The conducted studies made it possible to create additional risk stratification scales, for example, Cardiovascular Event Risk Test (CERT) 1 and 2. They make it possible to estimate the residual risk in patients taking statins. The lipidome examination in extracranial artery atherosclerosis can identify those plaques that have signs of instability, and therefore are dangerous for ischemic stroke development.The review describes the features of plasma lipidome in various cardiovascular diseases associated with atherosclerosis.

Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study

ObjectivesCompare the risk of extended major adverse cardiovascular (CV) event (MACE) composite outcomes and component events in patients with rheumatoid arthritis (RA) treated with tofacitinib versus tumour necrosis factor inhibitors...

The Net Clinical Outcome of Dual-Pathway Inhibition in Clinical Practice: The "Xarelto plus Acetylsalicylic Acid: Treatment Patterns and Outcomes in Patients with Atherosclerosis" Registry.

Background: In the COMPASS trial, the combination of acetylsalicylic acid (ASA) plus 2.5 mg rivaroxaban twice daily (dual-pathway inhibition, DPI) has been shown to be superior to ASA monotherapy for the reduction in ischemic major adverse cardiovascular events (MACEs, i.e., cardiovascular death, stroke, or myocardial infarction). Methods: The international XATOA registry (Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis) is a prospective post-approval registry that investigates the cardiovascular outcomes of patients taking ASA plus 2.5 mg rivaroxaban. The aim of this pre-specified analysis was to determine the net clinical outcome (NCO), i.e., a combination of MACEs and bleeding events, of DPI in patients from daily clinical practice. Results: Among the 5615 patients, the presence of multiple risk factors resulted in an increase in the total risk of experiencing an NCO event, e.g., from 1.27% (one risk factor) to 2.18% (two risk factors) and 4.07% (three or more risk factors), respectively, with ischemic MACE representing the primary driver of bleeding complications. Conclusions: In the real-world XATOA registry, the annual rate of NCO events was low and numerically similar to those seen in the treatment group in the randomized COMPASS trial.

Thrombotic Complications, Disease Progression, and Survivals in BCR::ABL1-Negative Myeloproliferative Neoplasms: A 12-Year Retrospective Study at a Single Center in Thailand

Objective: To assess the incidence of thrombotic events among patients with BCR::ABL1-negative myeloproliferative neoplasm (MPN) within a single center in Thailand. Materials and Methods: Conducted as a retrospective cohort study between 2008 and 2019, the present research focused on patients diagnosed with BCR::ABL1-negative MPN. Diagnoses were reviewed and reclassified based on the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2017). Data collected encompassed demographic details, comorbidities, investigation results, treatments, and outcomes. The primary focus was on thrombosis rates in arterial and venous sites. Secondary outcomes included the incidence of major bleeding, thrombosisfree survival (TFS), and overall survival (OS). Results: One hundred seventy-five patients participated in the present study and comprised of 46 patients (26.3%) with polycythemia vera (PV), 123 (70.3%) patients with essential thrombocythemia (ET), and six patients (3.4%) with primary myelofibrosis (PMF). Most patients were over 60 years old. The rate of overall thrombosis rate was 28.0%, with 43.5% in PV and 23.6% in ET. Common sites of thrombotic events included the cerebral artery at 16.6%, coronary artery at 6.3%, peripheral artery at 4.0% and venous thromboembolism at 3.4%. The overall bleeding event rate was 13.7%, with 70.8% classified as major bleeding. The all-cause mortality rate within the present cohort was 30.9%. TFS and OS stood 72.0% and 69.1%, respectively. Conclusion: Thrombosis emerged as a significant complication in patients with BCR::ABL1-negative MPN, affecting 28.0% of individuals in the present cohort. Arterial thromboses, particularly ischemic stroke and cardiovascular events, were the predominant occurrences. Keywords: Myeloproliferative neoplasm; Polycythemia vera; Essential thrombocythemia; Thrombosis; Bleeding

Abstract WP151: Prevailing Income-Based Disparities in Acute Ischemic Stroke and Cardiovascular Events in Young Hospitalized Adults With Cannabis Use Disorder: Insights From a Population-Based Analysis

Introduction: Cannabis use and low socioeconomic status are recognized as distinct risk factors for stroke and cardiovascular pathologies. This observational study aims to investigate the association between income status in acute ischemic stroke (AIS) and cardiovascular events among young, hospitalized adults with dependent cannabis use or cannabis use disorder (CUD). Methods: We analyzed young adult hospitalizations (18-44 years) with known CUD from the 2020 National Inpatient Sample. Propensity score-matched analysis (1:1) was used to compare comorbidities, including AIS and cardiovascular events, between the high-income quartile (HIQ) and low-income quartile (LIQ) within the CUD cohort. Results: Out of the young adult admissions, a total of 286,855 individuals were identified as dependent cannabis users. After propensity matching, we divided the CUD cohort into 63,355 patients with HIQ (41.1% female) and LIQ (41.4% female). While both cohorts exhibited comparable ages and racial distribution (>65% white), the individuals from LIQ cohort were predominantly from South (45.7% vs. 27.9%), visiting rural hospitals (13.9% vs. 1.3%), with Medicaid (56.3% vs. 41.1%) as the predominant payer. Additionally, LIQ cohort had a higher prevalence of drug abuse (65.5% vs. 58.4%), tobacco use (24.9% vs. 22.6%), HTN (17% vs. 14.7%), chronic pulmonary disease (13.2% vs. 12.7%), DM (8% vs. 6.6%), and obesity (10.9% vs. 10.0%). Additionally, in-hospital outcomes like AIS (0.5% vs. 0.3%) and MACCE (2% vs. 0.8%) were higher in the LIQ cohort. After adjusting for confounding factors, the risk of AIS in the HIQ cohort was 37% lower than in the LIQ cohort (OR: 0.63 [95% CI: 0.42-0.96]). (all-p<0.05). Conclusion: Higher prevalence of CVD risk factors in the LIQ-CUD group and lower odds of AIS-related admissions in the HIQ-CUD group warrant targeted interventions and policy measures to understand and address behavioral risk of cannabis use by economic status and disparities in MACCE.

Abstract WP229: Comparing the Real-World Effects of Once-Weekly Semaglutide and Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcomes, Health Care Resource Utilization, and Medical Costs in Individuals With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

When compared with placebo, glucagon-like peptide-1 receptor agonists such as once-weekly semaglutide (semaglutide OW T2D) improve cardiovascular outcomes in people with type 2 diabetes (T2D), whereas dipeptidyl peptidase-4 inhibitors (DPP-4is) do not. However, no head-to-head trials of these 2 incretin-based drug classes have been conducted. This retrospective cohort study used 2018-2022 data from the Optum ® Clinformatics ® Data Mart to compare on-treatment time with incidence of ischemic stroke, myocardial infarction (MI), and 2-point major adverse cardiovascular events (MACE; composite of ischemic stroke and MI); health care resource utilization; and medical costs in new adult users of semaglutide OW T2D and DPP-4is with T2D and atherosclerotic cardiovascular disease (ASCVD). Patients were followed until drug discontinuation, enrollment end, or an event. Baseline characteristics ( Table ) were balanced using inverse probability of treatment weighting. On average, patients were aged 70 years, with 5.6- and 4.3-year history of T2D and ASCVD, respectively. Survival analyses were conducted to compare risks during exposure. Users of semaglutide OW T2D (weighted n=14,461) had 46%, 36%, and 40% lower relative risk of ischemic stroke, MI, and 2-point MACE, respectively, compared with users of DPP-4is (weighted n=38,630; all P ≤0.001; Figure ). Users of semaglutide OW T2D also had decreased ASCVD-related and all-cause hospitalizations, outpatient visits, hospitalization costs, and total medical costs (all P <0.05). This study suggests that semaglutide OW T2D reduces the risk of stroke and MI while reducing medical costs relative to DPP-4is in adults with T2D and ASCVD.

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis.

Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited. To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism). We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials. We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI. Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale. We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation. Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.

Biochemical profiles and risk of cardiovascular events in patients withType 2 Diabetes: implications for choice of novel antihyperglycemic therapy

Abstract Background Guidelines on type 2 diabetes (T2D) recommend targeting patients at greater risk of heart failure with sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and patients at greater risk of cardiovascular ischemic events with glucagon-like peptide-1 receptor agonists (GLP1-RA) or SGLT2-i. It is currently unclear whether distinct biochemical profiles are more or less associated with the occurrence of heart failure or a cardiovascular ischemic event. Purpose To investigate the risk of the first occurring event of either heart failure or a cardiovascular ischemic event associated with different biochemical profiles in newly diagnosed T2D patients without cardiovascular disease. Methods From Danish nationwide registers, we identified all patients newly diagnosed with T2D who were free of cardiovascular disease (heart failure, ischemic heart disease, peripheral artery disease, and previous stroke), from 2013-2021. Patients <40 years, and patients without a registered blood test within three months prior to the T2D diagnosis, were excluded. The absolute 5-year risk of the first occurring event of either heart failure or a cardiovascular ischemic event, was calculated for patients with different levels of three biochemical markers that are known to be associated with cardiovascular disease: 1) HbA1c 2) low-density lipoprotein (LDL); and 3) estimated glomerular filtration rate (eGFR) calculated from serum creatinine. Results Of the 81,095 patients included in the study, 53% were male and the median age was 60 years [interquartile range 52-69]. For all pre-defined biochemical profiles—HbA1c below or above 8%, LDL below or above 4 mmol/L, and eGFR below or above 60ml/min/1.73m2—the absolute 5-year risk of a cardiovascular ischemic event was greater than the risk of heart failure (risk ratio ranging from 2.3–4.2), as the first occurring event following the diagnosis of T2D. The highest risk of heart failure was observed in those with moderately to severely reduced eGFR (<60 ml/min/1.73m2). Conclusions Among patients newly diagnosed with T2D and free of cardiovascular disease, different biochemical profiles of HbA1c, LDL, and eGFR, were all associated with a higher risk of an ischemic cardiovascular event as the first occurring event following T2D diagnosis, as opposed to heart failure.Flowchart of patient selectionCumulative incidence of CIE Vs. HF

Two of a kind: mass and molar immunoassay-based lipoprotein (a) concentrations are similarly prognostic for MACE risk and predictive of alirocumab benefit in ODYSSEY OUTCOMES

Abstract Background Lipoprotein (a) (Lp(a)) is a risk factor for incident and recurrent ischemic cardiovascular (CV) events and may modify the benefit of PCSK9 inhibitors (PCSK9i). While Lp(a) concentration can be measured in either mass or molar units, to date there has been no direct, large-scale comparison of the relationships of mass vs. molar Lp(a) with CV risk and response to treatment. Purpose Using samples from ODYSSEY OUTCOMES where 18,924 patients with recent acute coronary syndrome were randomized 1:1 to the PCSK9i alirocumab (ALI) or placebo (PBO), baseline mass vs. molar Lp(a) were compared in terms of prognosis for first major adverse CV event (MACE, consisting of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) in the placebo group and associations with ALI risk reduction. Methods Lp(a) mass and molar tests were the Siemens N latex immunonephelometric test and the Roche TinaQuant immunoturbidimetric assay, respectively. Both tests use polyclonal anti-apo(a) antibodies but are designed to be relatively apo(a)-size independent within allowable measurement uncertainty. Absolute risk of MACE at 4 years in the PBO group and treatment risk ratios (RR) by continuous Lp(a) concentrations were estimated by natural cubic splines from Poisson regression models with log follow-up time as an offset and adjustment for baseline LDL-C. For comparative modeling purposes Lp(a) values were transformed into percentiles; due to ties at the lower limits of quantification, minimum percentiles were 8th and 6th for mass and molar, respectively. All analyses were intention-to-treat. Results Baseline mass and molar Lp(a) concentrations, available in 11943 patients, were correlated (r=0.94). ALI MACE reduction in evaluable patients (1324 events; RR [95% CI] = 0.83 [0.74, 0.92]) was similar to the total population (1955 events; RR [95% CI] = 0.85 [0.78, 0.93]). Relationships with risk of MACE in the PBO group were nearly identical for mass (spline p=0.0001) and molar (spline p=0.0002) concentrations (Figure 1). Of note, the confidence boundaries around the splines were nearly superimposable, indicating similar precision of the estimated Lp(a)-associated risk with both measurement techniques. Risk reductions with ALI were similarly related to mass (spline p<0.0001) and molar (spline p<0.0001) concentrations (Figure 2). Conclusion Baseline mass and molar Lp(a) concentrations were similarly prognostic for MACE risk in the PBO group after adjustment for LDL-C. Mass and molar Lp(a) also similarly modified the ALI treatment effect on MACE, with trends towards less treatment benefit at lower concentrations. These results suggest that, at the treatment group level, the prognostic and predictive value of immunoassay-based Lp(a) tests for ischemic CV events in patients with recent acute coronary syndrome is not meaningfully different for the mass or molar concentration essays that were evaluated.Figure 1Figure 2

Haptoglobin 1 gene polymorphism protects against postoperative cardiovascular events

Abstract Background Haptoglobin (Hp) is a plasma glycoprotein with antioxidant properties that plays a role in maintaining the integrity of the bloodstream and in clearing plasma lipids. The human haptoglobin gene is polymorphic, with two prevalent alleles (Hp1 and Hp2) resulting in three distinct phenotypes. The Hp subtypes have been linked to the risk of symptomatic carotid stenosis and major ischemic cardiovascular events, with some studies suggesting a protective role of the Hp1 allele. However, observed discrepancies in the relationship between Hp genotype and cardiovascular events suggest the presence of additional underlying mechanisms or differences among Hp1 allele subtypes. This study aims to examine the role of Hp1 alleles (Hp1F and Hp1S) in atherosclerosis and determine their association with cardiovascular events in our cohort of carotid endarterectomy patients. Methods The study included a total of 691 patients who underwent a carotid endarterectomy. All patients underwent genotyping for Haptoglobin. A total of 668 carotid plaques were collected, and 45 of these plaques were randomly selected for histopathological analysis and underwent staining for lipids using (Oil Red O), hemorrhage (glycophorin A), macrophages (CD68 [cluster of differentiation 68]), smooth muscle cells (alpha-actin) and collagen (Movat pentachrome). Participants were subsequently followed-up for postoperative cardiovascular events using data from clinical registers. The median follow-up for cardiovascular events was 48 months. All included patients gave written informed consent. The study was approved by the local ethical review board and followed the declaration of Helsinki. Results There were no significant differences in the baseline clinical characteristics between Hp1S carriers (36.6%) and non-carriers (63.4%). Postoperative cardiovascular and mortality events were found to be significantly associated with Hp1S subtype, with carriers exhibiting a decreased risk (HR=0.372, 95%CI 0.180-0.769, p=0.008). The histological examination of the plaques revealed that Hp1S carriers had a significantly greater percentage of plaque area stained positive alpha-actin (p=0.033). However, there were no significant differences observed in other histological markers. Conclusions Hp1S was associated with lower risk of postoperative cardiovascular events in our cohort of carotid endarterectomy patients. Patients with this genotype had plaques with more smooth muscle cells, so possibly more stable. This suggests that Hp1 subtypes could be of interest in risk stratification of this patient population, deserving further studies.

Antithrombotic and Statin Prescription After Intracerebral Hemorrhage in the Get With The Guidelines-Stroke Registry.

Survivors of intracerebral hemorrhage (ICH) face an increased risk of ischemic cardiovascular events. Current ICH guidelines do not provide definitive recommendations regarding the use of antithrombotic and statin therapies. We, therefore, sought to study practice patterns and factors associated with the use of such medications after ICH. This was a cross-sectional study of patients with ICH in the Get With The Guidelines-Stroke registry, between 2011 and 2021. Patients transferred to another hospital, those who died during hospitalization, and those with missing information on discharge medications were excluded. The study exposure was the proportion of patients who were prescribed antithrombotic or statin medications. We first ascertained the proportion of patients prescribed antithrombotic and lipid-lowering medications at discharge overall and across strata defined by pre-ICH use and history of previous ischemic vascular disease or atrial fibrillation. We then studied factors associated with the discharge prescription of these medications after ICH, using multiple logistic regressions. In the final cohort, 50 416 (10.4%) of 486 586 patients with ICH were prescribed antiplatelet medications, 173 322 (35.1%) of 493 491 patients with ICH were prescribed statins, and 27 085 (5.4%) of 486 585 patients with ICH were prescribed anticoagulation therapy at discharge. The proportion of patients with antiplatelet therapy was 16.6% with pre-ICH use and 15.6% in those with previous ischemic vascular disease. Statins were prescribed to 41.1% and 43.7% of patients on previous lipid-lowering therapy and ischemic vascular disease, respectively. Anticoagulation therapy was restarted in 11.1% of patients. In logistic regression analysis, factors associated with higher use of antithrombotic or statin therapies after ICH were younger age, male sex, pre-ICH medication use, previous ischemic vascular disease, atrial fibrillation, lower admission National Institutes of Health Stroke Scale, longer length of stay, and favorable discharge outcome. Few patients with ICH are prescribed antithrombotic or statin therapies at hospital discharge. Given the emerging association between ICH and future major cardiovascular events, trials examining the net benefit of antiplatelet and lipid-lowering therapy after ICH are warranted.

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis

Abstract Background Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging and the optimal antithrombotic therapy remains uncertain. The potential of NOACs to prevent ischaemic cardiovascular events is promising but evidence remains limited. Purpose To assess the efficacy and safety of NOACs in addition to background antiplatelet therapy for secondary prevention post-AMI in people without an indication for anticoagulation. Methods We performed a systematic literature search in September 2022, assessed each included RCT, extracted study data and conducted a network meta-analyses (NMA) using the R package 'netmeta'. Results We included six RCTs, with 33,039 participants. Moderate to high-certainty-evidence suggests rivaroxaban reduces all-cause mortality (RR 0.82, 95% CI 0.69 to 0.98) and probably reduces cardiovascular death (RR 0.83, 95% CI 0.69 to 1.01). Low-certainty-evidence suggests dabigatran may reduce all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06). There is probably little or no difference in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35) and cardiovascular death (RR 0.99, 95% CI 0.77 to 1.27) between apixaban and placebo. There is uncertainty about the rate of cardiovascular death with dabigatran compared with placebo, as the point estimate might suggest benefit (RR 0.72, 95% CI 0.34 to 1.52). Moderate to high-certainty-evidence suggests that NOACs (specifically apixaban and rivaroxaban) probably increase major bleeding compared with placebo (apixaban vs placebo: RR 2.41, 95% CI 1.44 to 4.06, rivaroxaban vs placebo: RR 3.31, 95% CI 1.12 to 9.77). The evidence is uncertain about the risk of major bleeding with dabigatran (dabigatran vs placebo: RR 1.74, 95% CI 0.22 to 14.12). The results from the NMA were inconclusive between the different NOACs in all individual doses for all primary outcomes. However, low-certainty-evidence suggests that apixaban (combined dose) might not be as effective as rivaroxaban or dabigatran in preventing all-cause mortality after AMI in people without an indication for anticoagulation. Conclusions Moderate to high-certainty-evidence suggests rivaroxaban reduces all-cause mortality and probably reduces cardiovascular death after AMI. Low-certainty evidence suggests dabigatran may reduce all-cause mortality. Moderate-certainty evidence suggests no meaningful difference in the rate of all-cause mortality and cardiovascular death between apixaban and placebo. Moreover, no meaningful benefit in efficacy outcomes was detected for specific therapy doses for any of the NOACs following AMI in people without an indication for anticoagulation. Moderate to high-certainty evidence suggests that NOACs probably increase major bleeding compared with placebo. Our network meta-analysis did not show superiority of one NOAC over another for any primary outcome. Head-to-head trials, comparing NOACs against each other, are required to provide more certain evidence.

Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage.

This focused update about antiplatelet agents to reduce the high risk of major adverse cardiovascular events after stroke due to spontaneous (nontraumatic) intracerebral hemorrhage (ICH) complements earlier updates about blood pressure-lowering, lipid-lowering, and oral anticoagulation or left atrial appendage occlusion for atrial fibrillation after ICH. When used for secondary prevention in people without ICH, antiplatelet agents reduce the risk of major adverse cardiovascular event (rate ratio, 0.81 [95% CI, 0.75-0.87]) and might increase the risk of ICH (rate ratio, 1.67 [95% CI, 0.97-2.90]). Before 2019, guidance for clinical decisions about antiplatelet agent use after ICH has focused on estimating patients' predicted absolute risks and severities of ischemic and hemorrhagic major adverse cardiovascular event and applying the known effects of these drugs in people without ICH to estimate whether individual ICH survivors in clinical practice might be helped or harmed by antiplatelet agents. In 2019, the main results of the RESTART (Restart or Stop Antithrombotics Randomized Trial) randomized controlled trial including 537 survivors of ICH associated with antithrombotic drug use showed, counterintuitively, that antiplatelet agents might not increase the risk of recurrent ICH compared to antiplatelet agent avoidance over 2 years of follow-up (12/268 [4%] versus 23/268 [9%]; adjusted hazard ratio, 0.51 [95% CI, 0.25-1.03]; P=0.060). Guidelines in the United States, Canada, China, and the United Kingdom and Ireland have classified the level of evidence as B and indicated that antiplatelet agents may be considered/reasonable after ICH associated with antithrombotic agent use. Three subsequent clinical trials have recruited another 174 participants with ICH, but they will not be sufficient to determine the effects of antiplatelet therapy on all major adverse cardiovascular events reliably when pooled with RESTART. Therefore, ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage) aims to recruit 4148 ICH survivors to determine the effects of antiplatelet agents after ICH definitively overall and in subgroups.