Reduction In Clinical Events Research Articles

Cost-Effectiveness of Radiofrequency Renal Denervation for Uncontrolled Hypertension in Japan.

Radiofrequency renal denervation (RF RDN) is a novel therapy for uncontrolled hypertension. In the recent sham-controlled SPYRAL HTN-ON MED study, office-based systolic blood pressure (oSBP) and nighttime BP were reduced significantly. This study examined the cost-effectiveness of RF RDN in the context of the Japanese healthcare system based on this latest clinical evidence. Clinical events, costs, and quality-adjusted life-years (QALYs) were projected using a decision-analytic Markov model adjusted to Japanese incidence data. Risk reduction in clinical events from changes in oSBP was calculated based on a published meta-regression of 47 trials of intentional hypertension treatment. Demographics and results from the SPYRAL HTN-ON MED trial (oSBP effect size -4.9mmHg vs. sham) were utilized in the base case analysis. Additional scenarios were explored including the potential added benefit of improved night-time control. Costs were sourced from claims data and published literature. The incremental cost-effectiveness ratio (ICER) was evaluated against a cost-effectiveness threshold of ¥5000000 per QALY gained. RF RDN was projected to reduce clinical events (10-year relative risks: 0.80 for stroke, 0.88 for myocardial infarction, and 0.75 for heart failure). Over lifetime, RF RDN added 0.36 QALYs at the incremental cost of ¥923723, resulting in an ICER of ¥2565236 per QALY gained. Under the assumption of added night-time benefit, the ICER decreased to ¥2155895 per QALY. Cost-effectiveness findings were robust across all tested scenarios. The findings of this model-based analysis suggest that RF RDN can provide meaningful clinical event reductions and is a cost-effective treatment option in the Japanese healthcare system.

The relative importance of ischaemia and scar in the genesis of ventricular arrhythmia in ischaemic cardiomyopathy

Abstract Background Ventricular arrhythmias are a leading cause of death in patients with ischaemic cardiomyopathy (ICM). Ischaemia and scar are thought to contribute to arrhythmogenesis; as scar is considered fixed, strategies to reduce ischaemia such as revascularisation are undertaken to attempt to reduce risk, despite limited evidence behind this practice. Purpose The study rationale was to understand the relative contributions of ischaemia and scar on the genesis of arrhythmia in an ICM population, by undertaking a detailed assessment of arrhythmic substrate in a highly characterised population and secondly by validating these findings in a large cohort. Methods We assessed the relationship between scar, ischaemic burden and impact of ischaemia modulation via revascularisation on the arrhythmic substrate (study 1) and major arrhythmic events (study 2). S1: Patients were eligible for enrolment if they had an LVEF≤40%, extensive coronary disease (BCIS Jeopardy Score (JS) ≥6) and were due to undergo CABG or PCI. Arrhythmic substrate was characterised by the LV activation recovery interval (ARI) dispersion recorded by electrocardiographic imaging (ECGi). Scar and ischaemic burden were assessed via stress perfusion cardiac magnetic resonance (pCMR) imaging, calculated as a percentage of total LV myocardial volume. ECGi and pCMR were repeated 3 months post revasc. S2: Arrhythmia data were collected from device interrogation reports and blinded core lab analyses performed of CMR scans and angiograms of patients enrolled in the REVIVED-BCIS2 trial. Extent of revasc (quantified by change in JS/baseline JS) was used to estimate change in ischaemic burden. The primary outcome was death or aborted sudden death. Results S1: 30 patients were recruited; age 67±10 years, 87% male, BMI 28±5. Baseline LV ARI dispersion at rest was correlated with scar burden (r=0.37, p=0.04) but not ischaemic burden (r=0.25,p=0.21). Changes in metrics are shown(Table 1). Ischaemic burden reduced after revascularisation. Delta ischaemic burden was correlated with delta LV ARI dispersion (r=0.51, p=0.007 unadjusted). S2: Data was collected on 479 patients from REVIVED-BCI2 who underwent CMR; age 69±9 yrs, 88% male, BMI 28±6, LVEF 26±8%. 237 were randomised to PCI and 242 to OMT; no difference in rates of all-cause death, CV death, aborted sudden death, appropriate device therapy or arrhythmia was identified between the groups. Scar burden was associated with death or aborted sudden death, extent of revascularisation was not(Figure 1). Conclusion In our studies, the volume of scar was strongly related to both the arrhythmic substrate and occurrence of arrhythmic events. Whilst ischaemia reduction affected the arrhythmic substrate, this did not translate to a reduction in clinical events. These findings suggest that scar burden, rather than ischaemia reduction by revascularisation, should be the focus of risk stratification and therapeutic decision making in patients with ICM.Table 1Figure 1

Catheter-Based Radiofrequency Renal Denervation in the United States: A Cost-Effectiveness Analysis Based on Contemporary Evidence

BackgroundCatheter-based radiofrequency renal denervation (RF RDN) has recently been approved as an adjunctive treatment for hypertensive patients without adequate blood pressure control. This study assessed the cost-effectiveness of RF RDN in the United States based on contemporary clinical evidence. MethodsA decision-analytic Markov model projected costs, quality-adjusted life years (QALY), and clinical events for an active cohort treated with RF RDN and a control cohort treated with standard-of-care (defined as 1, 2, or 3 antihypertensive medications). Cohort demographics and therapy effect were derived from the SPYRAL HTN-ON MED study demonstrating an absolute 9.9 mm Hg reduction in office systolic blood pressure and 4.9 mm Hg reduction compared with sham control. Clinical event risk reduction from blood pressure lowering was based on a meta-regression of 47 hypertension trials. The incremental cost-effectiveness ratio was evaluated against willingness-to-pay thresholds of $50,000 per QALY (high value) and $150,000 per QALY (intermediate value). Extensive scenario and sensitivity analyses were conducted to assess robustness of the findings. ResultsRF RDN yielded a significant risk reduction in clinical events (0.80 for stroke, 0.88 for myocardial infarction, and 0.85 for cardiovascular death over 10 years). Over lifetime, RF RDN added 0.34 QALY at an additional cost of $11,275, leading to an incremental cost-effectiveness ratio of $32,732 per QALY. The cost-effectiveness of RF RDN was robust across a broad range of scenarios and sensitivity analyses. ConclusionsBased on a lifetime projection, catheter-based RF RDN is a cost-effective, high-value intervention for hypertensive patients with uncontrolled hypertension.

Evolocumab Treatment in Dyslipidemic Patients Undergoing Coronary Artery Bypass Grafting: One-Year Safety and Efficacy Results.

Background: The inhibition of PCSK9 lowered LDL cholesterol levels, reducing the risk of cardiovascular events. However, the effect on patients who have undergone surgical myocardial revascularization has not yet been evaluated. Methods: From January 2017 to December 2022, 180 dyslipidemic patients who underwent coronary artery bypass were included in the study. Until December 2019, 100 patients optimized therapy with statin ± ezetimibe (SG). Since January 2020, 80 matched patients added treatment with Evolocumab every 2 weeks (EG). All 180 patients were followed-up at 3 and 12 months, comparing outcomes. Results: The two groups are homogenous. At 3 months and 1 year, a significant decrease in the parameter mean levels of LDL cholesterol and total cholesterol is detected in the Evolocumab group compared to the standard group. No mortality was detected in either group. No complications or drug discontinuation were recorded. In the SG group, five patients (5%) suffered a myocardial infarction during the 1-year follow-up. In the EG group, two patients (2.5%) underwent PTCA due to myocardial infarction. There is no significant difference in overall survival according to the new treatment (p-value = 0.9), and the hazard ratio is equal to 0.94 (95% C.I.: [0.16-5.43]; p-value = 0.9397). Conclusions: The use of Evolocumab, which was started immediately after coronary artery bypass graft surgery, significantly reduced LDL cholesterol and total cholesterol levels compared to statin treatment alone and is completely safe. However, at one year of follow-up, this result did not have impact on the reduction in major clinical events.

Sex-based outcomes on unguided de-escalation from ticagrelor to clopidogrel in stabilized patients with acute myocardial infarction undergoing percutaneous coronary intervention: a post-hoc analysis of the TALOS-AMI.

The TALOS-AMI study highlighted the effectiveness of a de-escalation strategy shifting from ticagrelor to clopidogrel 1 month after percutaneous coronary intervention (PCI), resulting in significant reduction in clinical events, primarily attributed to a substantial decrease in bleeding events. Nevertheless, the impact of this strategy on outcomes based on sex remains unclear. This was a post-hoc analysis of the TALOS-AMI study. At 1 month after PCI, patients who remained adherent to aspirin and ticagrelor without experiencing major adverse events were randomized into either the de-escalation group (clopidogrel plus aspirin) or the active control group (ticagrelor plus aspirin) for an additional 12 months. The primary endpoint encompassed a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2 or greater at 12 months after randomization. Among the 2,697 patients included in this study, 454 (16.8%) were women. Women, characterized by older age and a higher prevalence of hypertension, diabetes, impaired renal function, and non-ST-segment myocardial infarction, exhibited a lower primary endpoint at 12 months compared to men [adjusted hazards ratio (HR), 0.60; 95% confidence interval (CI), 0.37-0.95; P = 0.03]. Compare to the active control group, the de-escalation group demonstrated a reduced risk of the primary endpoint in both women (adjusted HR, 0.38; 95% CI, 0.15-0.95; P = 0.039) and men (adjusted HR, 0.56; 95% CI, 0.40-0.79; P = 0.001) (interaction P = 0.46). In stabilized patients post-PCI with drug-eluting stents for acute myocardial infarction, the primary endpoint was lower among women compared to men. In this cohort, the benefits of an unguided de-escalation strategy from ticagrelor to clopidogrel were comparable in women and men.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

Design of knowledge-based mechanistic model of atherosclerotic cardiovascular disease for in silico trials

Abstract In silico trials applying a computational model (CM) of atherosclerotic cardiovascular disease (ASCVD) to virtual patients receiving alternative treatments provide an attractive option to complement randomised clinical trials (RCTs) by adding comparative effectiveness data and facilitating the demonstration of drug benefit. In silico modelling allows comparison between treatments with each virtual patient being his own control, and is not limited by the number of patients, comparative arms or trial duration. This study aims at building a knowledge-based mechanistic model of ASCVD. Once validated, the model will be used to run in silico clinical trials to compare the benefit of inclisiran, an siRNA targeting PCSK9 mRNA, vs other lipid-lowering therapies (LLT) on cardiovascular (CV) events in patients with ASCVD. An extensive literature review was performed to identify pathophysiological mechanisms involved in ASCVD and therapeutic mechanisms of action (MOAs). Every piece of knowledge extracted from the literature is awarded a strength of evidence grading to allow tracking of uncertainty in the model. A panel of multidisciplinary experts reviewed knowledge models and subsequent modelling hypotheses to validate their relevance. Knowledge was translated into mathematical equations. Each functional relationship between entities is represented by a biochemical/biophysical reaction with its reaction rate. A system of ordinary differential equations provides dynamics of modelled biological entities. A strategy of model calibration/validation was defined with the expert panel, by selecting relevant RCT and registry data, that the model should be able to reproduce. A virtual population was generated to account for inter-patient variability. A mechanistic CM of ASCVD (including 72 biological entities, 750 parameters) was built from knowledge, describing lipoproteins metabolism and cholesterol homeostasis, dynamics of atherosclerotic plaque growth with lipoproteins infiltration in the intima and evolution of lipidic, necrotic and fibrotic tissues as well as plaque rupture leading to myocardial infarction, ischemic stroke, lower extremity arterial disease or CV death. It also includes the impact of several risk factors (age, sex medical history, diabetes, hypertension, smoking, systemic inflammation, chronic kidney disease) and available LLT (atorvastatin, rosuvastatin, ezetimibe, evolocumab and inclisiran). After calibration, the model and virtual population reproduce pharmacokinetics of LLT, lipoproteins decrease under combinations of LLT and associated reduction in clinical events. ASCVD is ideally suited for in silico modelling: extensive literature is available regarding the pathophysiology, therapeutic MOAs are known and easily integrated in the model, clinically relevant outcomes are adequate model outputs, RCT and registry data exist to calibrate/validate the model. The next step is validation of the model before using it to run in silico trials.Plaque growth and rupture modelMulti-scale in silico model

Mortality with bivalirudin plus a high-dose infusion versus heparin in patients with acute coronary syndrome

Abstract Background The use of bivalirudin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has been downgraded by recent international guidelines. The reason for this downgrade lies above all on the excess of acute stent thrombosis (ST) associated with bivalirudin, but subsequent studies have suggested that a post-PCI high-dose bivalirudin infusion may mitigate the risk of acute ST related to the short half-life of bivalirudin. Methods We performed an updated meta-analysis of RCTs comparing bivalirudin followed by a post-PCI high-dose infusion versus UFH in ACS. Four RCTs accounting for a total of 16,920 patients were included. Odds ratios (OR) with 95% confidence intervals (CIs) using random effect models were calculated. Number needed to treat (NNT) were also calculated. Clinical outcomes at 30 days were included in the analysis. Results Four RCTs accounting for a total of 16,920 patients were included. We found that bivalirudin is associated with a non-significant reduction of 30-day all-cause death (OR 0.81, 95% CI 0.56-1.16, NNT 250, I2 53%), compared with UFH. Results were consistent at a subgroup analysis of STE-ACS versus NSTE-ACS and in a sensitivity analysis excluding the VALIDATE-SWEDEHEART, the only study using a shorter post-PCI bivalirudin infusion (mean 57 min) that was not used in the totality of patients (65%). Moreover, bivalirudin followed by a high-dose infusion was associated with a significant reduction of net adverse clinical events (NACE) (OR 0.62, 95% CI 0.42-0.90, NNT 31, I2 87%) as defined in each trial and of ST (OR 0.47, 95% CI 0.31-0.71, NNT 200, I2 1%), compared with UFH. Finally, BARC 3-5 bleeding was non-significantly reduced (OR 0.36, 95% CI 0.12-1.02, NNT 143, I2 82%) with bivalirudin compared with UFH. Conclusion We conclude that bivalirudin followed by a high-dose infusion is associated with reduced ST and NACE compared with UFH, but whether it may reduce all-cause mortality requires further investigations.

Abstract 12511: Efficacy of Bivalirudin versus Heparin Use on Clinical Outcomes Post Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials

Background: For patients undergoing percutaneous coronary intervention (PCI), Bivalirudin has been shown to reduce major bleeding, however, unfractionated heparin is currently considered the standard of care. Objective: We sought to perform an updated meta-analysis comparing the efficacy of bivalirudin versus heparin undergoing PCI with the inclusion of the most recently published trials. Methods: A systematic literature search was performed in PubMed, Embase, and Clinicaltrial.gov from inception to 10th May 2023 for studies comparing bivalirudin vs. heparin among PCI-undergoing patients. Pooled odds ratios (OR) were calculated using a random effect model, and a p-value of <0.05 was considered statistically significant. Results: A total of 14 randomized controlled trials with 35,533 patients (17765 in Bivalirudin treated group and 17768 patients in Heparin treated group). The pooled analysis shows that bivalirudin was associated with significant 21% reduction in net adverse clinical events (NACE) (OR, 0.79(95%CI: 0.71-0.88), P<0.01), cardiovascular mortality (CVM) by 24% (OR, 0.76(95%CI: 0.65-0.90), P<0.01), major bleeding by 36% (OR, 0.64(95%CI: 0.49-0.83), P<0.01), transfusion by 42% (OR, 0.58(95%CI: 0.44-0.77), P<0.01) compared to heparin. There was a trend of reduced all-cause mortality among bivalirudin groups (OR, 0.86(95%CI: 0.72-1.02) compared to the heparin group of patients, however, it didn't reach statistical significance. Incidence of stroke, major adverse cardiovascular events, myocardial infarction, and stent thrombosis was comparable between both groups of patients. Conclusion: Bivalirudin has shown to be superior to heparin among patients undergoing PCI with a reduction in bleeding, CVM, NACE, and a trend of reduced all-cause mortality.

Cardiometabolic effect of sodium and glucosa cotransporter inhibitors type 2

Introduction: Type 2 diabetes mellitus has emerged as a leading cause of premature death and a growing threat to the healthcare system due to the high costs of medical care in the context of cardiovascular complications. Methods: We conducted a systematic electronic search of clinical trials published from 2015 to January 2023 in PubMed, Scopus, Web of Science and ScieLO databases, which evaluated the efficacy and safety of the use of type 2 sodium-glucose cotransporter inhibitors in patients with type 2 diabetes mellitus and established cardiovascular disease on routine treatment and their cost-effectiveness.Results: Significantly lower rates of acute myocardial infarction, stroke, cardiovascular death and hospitalization due to heart failure were observed when the study drugs were added to standard therapy. In addition, it was evidenced that the reduction in cardiovascular clinical events manages to offset the cost of type 2 sodium-glucose cotransporter inhibitors resulting in a cost-effective use of resources at the health care level.Conclusions: As the transition to a new evidence-based era of managing patients with type 2 diabetes mellitus and cardiovascular disease progresses, it is imperative that new therapies are developed that not only improve glycemic control, but also improve cardiovascular outcomes, because these events represent the major cause of mortality in this population.

Translating the efficacy of dapagliflozin in chronic kidney disease to lower healthcare resource utilization and costs: a medical care cost offset analysis

AimsDapagliflozin was approved for use in patients with chronic kidney disease (CKD) based on results of the DAPA-CKD trial, demonstrating attenuation of CKD progression and reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard therapy. The study objective was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes across 31 countries and regions.Materials and methodsA comparative cost-determination framework estimated outcome-related costs of dapagliflozin plus standard therapy versus standard therapy alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (HHF), acute kidney injury (AKI), and ACM were estimated for a treated population of 100,000 patients. Associated medical care costs for non-fatal events were calculated using sources from a review of publicly available data specific to each considered setting.ResultsPatients treated with dapagliflozin plus standard therapy experienced fewer incidents of ESKD (7,221 vs 10,767; number needed to treat, NNT: 28), HHF (2,370 vs 4,684; NNT: 43), AKI (4,110 vs. 5,819; NNT: 58), and ACM (6,383 vs 8,874; NNT: 40) per 100,000 treated patients versus those treated with standard therapy alone. Across 31 countries/regions, reductions in clinical events were associated with a 33% reduction in total costs, or a cumulative mean medical care cost offset of $264 million per 100,000 patients over 3 years.Limitations and conclusionsThis analysis is limited by the quality of country/region-specific data available for medical care event costs. Based on the DAPA-CKD trial, we show that treatment with dapagliflozin may prevent cardio-renal event incidence at the population level, which could have positive effects upon healthcare service delivery worldwide. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.

Patient Perspectives on a Tailored Self-Management Education and Support Intervention for Low-Income Seniors With Chronic Health Conditions

BackgroundThe Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study (ACCESS) was a 2 x 2 factorial randomized trial that tested the impact of a tailored self-management education support (SMES) program, which demonstrated a 22% reduction in adverse clinical events. We sought to qualitatively explore participants’ perspectives on the SMES intervention, and the ways in which it may have improved self-management skills. MethodsWe used a qualitative descriptive approach and conducted individual semistructured interviews. We conducted inductive and deductive thematic analysis using NVivo 12 (QSR International, Burlington, MA). ResultsWe interviewed 20 participants who had recently completed the 3-year SMES intervention. The following 3 main themes emerged from the data: (i) empowerment; (ii) intervention acceptability; and (iii) suggestions for improvement. Regarding empowerment, we identified subthemes of health literacy, self-efficacy, self-management, and active role in health. Several participants reported that empowerment promoted health behaviour change or improved confidence in self-management. Regarding acceptability, we identified subthemes of ease of use and presentation style. Most participants expressed positive feelings toward the intervention and felt that it was easy to understand. Finally, we identified subthemes of learning style, content, and engagement strategies, within the theme of suggestions for improvement. Some participants said that the messages were too general and did not fully address the complex health concerns they had. ConclusionsOur results highlighted key strategies to promote patient engagement and self-management behaviours and demonstrated how they may have been used to improve clinical endpoints. Additionally, we demonstrated the novel use of marketing principles in SMES interventions.

Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout.

People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.

Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence.

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies' clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future.

Meta-analysis of the effect of colchicine on C-reactive protein in patients with acute and chronic coronary syndromes.

The anti-inflammatory drug colchicine has recently shown benefits in the prevention of major adverse cardiovascular events (MACE) in patients with the acute coronary syndrome (ACS) and chronic coronary syndromes (CCS). This meta-analysis focuses on understanding Colchicine's effects on the high-sensitivity C-reactive protein (hs-CRP) to provide mechanistic insight to explain its clinical event reduction. A computerized search of MEDLINE was conducted to retrieve journal articles with studies performed on humans from 1 January 2005 to 1 January 2022, using keywords: 'Colchicine AND Coronary', 'Colchicine AND CRP', and 'Colchicine AND Coronary Artery Disease'. Studies were included if they measured hs-CRP changes from baseline, and colchicine or placebo were given to patients with ACS or CCS. Thirteen studies with a biomarker subgroup population of 1636 patients were included in the hs-CRP meta-analysis. Of those 13 studies, 8 studies with a total population of 6016 reported clinical events defined as myocardial infarction (MI), stroke, cardiovascular death, periprocedural MI, repeat angina after PCI and repeat revascularization. Multivariate analysis revealed a weak negative correlation of -0.1056 ( P = 0.805) between change in CRP and clinical events. Overall, colchicine treatment resulted in a greater reduction in hs-CRP levels compared with placebo (Mean Difference: -1.59; 95% Confidence Interval, -2.40 to -0.79, P = 0.0001) and clinical events (Odds Ratio: 0.78; 95% Confidence Interval 0.64 to 0.95, P = 0.01). Colchicine therapy is associated with a reduction in hs-CRP and clinical events in patients with ACS and CCS. This finding supports colchicine's anti-inflammatory efficacy via CRP reduction to explain its clinical benefit.

Abstract 10315: The Effect of Protease-Activated Receptor-1 Inhibition With Vorapaxar in Post-mi and Nstemi Patients on Selected Biomarkers Reflecting Endothelial Function

Introduction: Biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has essentially focused on platelets. Follow-up (FU) time has been short, whereas in the current study, focus has been on endothelial function during both short- and long-term PAR-1 inhibition. Aim: To assess short- and long-term effects of vorapaxar (V) as compared to Placebo (PL) on the following biomarkers: Angiopoietin-2 (ANGPT2), Angiopoietin-like 4 (ANGPTL4), VEGF, ICAM-1, VCAM-1, E-Selectin (ESEL), von Willebrand Factor (VWF), Thrombomodulin (TM), PAI-1 and PAI-2. Methods: In an independent collective subproject performed in Norway, post-MI patients at steady state were recruited from the “Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients with Atherosclerosis” (TRA2ᵒP-TIMI 50) and NSTEMI patients were recruited from the “Thrombin Receptor Antagonist for Clinical Event Reduction in acute coronary syndrome” (TRACER) trial. Biomarkers were measured in duplicate by enzyme immunoassays (EIA) in citrated plasma at one month follow-up and at study completion (median 2.3 years) for subjects recruited from both trials. Results: Biomarkers were measured in 265 consecutive patients [age median 62.0 years (Q1-Q3: 55.0-68.0 years), males 83%] with at least one change from baseline value. Among these, biomarkers were available at both short- and long-term follow-up in 221 subjects. ANGPT2 increased significantly in V as compared to PL at 1-month follow-up in the total population (p=0.034), and in males in both post-MI (p=0.031) and NSTEMI subjects (p=0.012), respectively. ANGPTL4 increased (p=0.028) and PAI-2 decreased (p=0.025) significantly in the total population in favor of V at final FU. In the total post-MI subgroup and among males of that group, a short-term significant increase in ESEL in favor of V was observed, p=0.029 and p=0.018, respectively. Also, a transient significant increase in VWF (p=0.032) in favor of V was seen at one month in NSTEMI patients. Conclusions: Significant changes suggesting potential harmful effects in some biomarkers were observed during 1-month and long-term PAR-1 inhibition as compared to placebo in post-MI and acute coronary syndrome patients.

Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes

BackgroundIn patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events. ObjectivesThis study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention. MethodsWe included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model. ResultsThere were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro–B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro–B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively. ConclusionsAn 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)

Economic evaluation of a vision-based patient monitoring and management system in addition to standard care for adults admitted to psychiatric intensive care units in England

Background and aims Treating patients in psychiatric intensive care units (PICUs) is costly for the English National Health Service (NHS), requiring significant staff time. Oxevision, a non-contact system, providing vision-based patient monitoring and management (VBPMM) has been introduced in some NHS mental health trusts which aims to help clinicians to deliver safer and more efficient care. The objective of this early economic evaluation was to explore the impact of introducing VBPMM with standard care, versus standard care alone on health and economic outcomes in PICUs across England. Methods The model uses a cost calculator approach to evaluate the potential benefits of introducing VBPMM, capturing differences in observation hours and critical events such as assaults. Effectiveness data were primarily based on a 24-month observational before and after study undertaken in an NHS mental health trust using VBPMM. Outcomes reported in this study are incremental costs and reduction in clinical events presented as per occupied bed days, per patient, per average ward, and for the English NHS overall. Scenario analysis was conducted to test the uncertainty of results using statistical significance of key inputs. Results and conclusions The analysis indicates that introducing VBPMM may be cost saving compared with standard care alone. The biggest driver of estimated cost savings was from the potential reduction in one to one observation hours, which may have significant impact in PICUs. Limitations of the analysis include the single center data underpinning the analysis and assumptions made about transferability of clinical data to different sized wards. Scenario analysis was conducted, and the results were robust to statistically significant changes in input parameters. This study suggests that introducing VBPMM on PICUs has the potential to reduce costs and improve efficiency of resource allocation, but results should be confirmed with additional clinical study evidence.

Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy.

REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in pathways known to associate with atherosclerosis risk. Serum levels of interleukin-1β, interleukin-6, high-sensitivity C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured at baseline, at 12 months, at 24 months, and at the end-of-study visit among REDUCE-IT participants with triglyceride levels ≥135 mg/dL and <500 mg/dL who were randomly allocated to treatment with either 4 grams daily of icosapent ethyl or mineral oil used as a comparator. At baseline, median levels of each biomarker were similar in the 2 treatment groups. The levels of biomarkers associated with atherosclerosis increased over time among those allocated to mineral oil treatment; in this group at 12 months, the median percent increases from baseline were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density lipoprotein cholesterol, 16.2% for interleukin-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein, and 28.9% for interleukin-1β (all P values <0.001), with similar changes at 24 months. In the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months. As such, at study conclusion, between-group treatment differences largely reflected increases in the mineral oil group with median percent differences of 2.4% for lipoprotein(a), 3.0% for homocysteine, 4.2% for oxidized low-density lipoprotein cholesterol, 19.8% for interleukin-6, 26.2% for Lp-PLA2, 38.5% for high-sensitivity C-reactive protein, and 48.7% for interleukin-1β (all P values ≤0.007). These data are consistent with previous REDUCE-IT results in which the median percent change for low-density lipoprotein cholesterol at 12 months was -1.2% among those allocated to icosapent ethyl and 10.9% among those allocated to the mineral oil comparator. Among participants in REDUCE-IT, allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels increased among those allocated to mineral oil. The effect of these findings on interpretation of the overall risk reductions in clinical events observed within REDUCE-IT is uncertain. URL: https://www. gov; Unique identifier: NCT01492361.

Outcomes After Acute Coronary Syndrome in Patients With Diabetes Mellitus and Peripheral Artery Disease (from the TRACER, TRILOGY-ACS, APPRAISE-2, and PLATO Clinical Trials)

Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.