Muscle quality and major adverse cardiovascular events in post-acute myocardial infarction: A prospective cohort study.

BACKGROUND & AIMS: Functional muscle quality, as assessed through the muscle quality index (MQI), represents a contemporary method to measure the capacity to generate force. Despite its potential, the prognostic significance of MQI remains uncertain in various clinical conditions, particularly among patients following acute myocardial infarction (AMI). In light of this, our study sought to evaluate the prognostic relevance of MQI concerning major adverse cardiovascular events (MACE) in patients following AMI. METHODS AND RESULTS: This is a secondary analysis of a prospective cohort study that included subjects aged ≥20 years from a Cardiovascular Unit Hospital. Functional muscle quality was estimated using MQI, defined as the ratio of handgrip strength (HGS) to muscle mass (MM) derived from bioelectrical impedance analysis. The outcomes included prolonged length of hospital stay, new adverse cardiovascular events (AMI, stroke and hospital readmission for unstable angina), and cardiovascular mortality. A composite score comprising all adverse events over the 1-year follow-up was calculated and defined as MACE. This study included 163 patients, with a median age of 61 years (IQ: 54-69 years), and the majority consisted of males (76.1%). Individual components of the functional muscle quality (HGS and MM) were not associated with any of the adverse outcomes. Only MQI was associated mortality over the 1-year follow-up. For each increase in MQI, the hazard of mortality decreases: adjusted HR: 0.08 (95% CI 0.01-0.84). CONCLUSION: Functional muscle quality assessed by the MQI may be a valuable clinical predictor of 1-year cardiovascular mortality in patients hospitalized post-AMI.

Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Revascularization is often performed in patients with stable ischemic heart disease. However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. METHODS: We conducted PUBMED/EMBASE/Cochrane Central Register of Controlled Trials searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with stable ischemic heart disease. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina, and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. RESULTS: Fourteen randomized clinical trials that enrolled 14 877 patients followed up for a weighted mean of 4.5 years with 64 678 patient-years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function and low symptom burden, and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (relative risk [RR], 0.99 [95% CI, 0.90-1.09]). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary, indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced nonprocedural MI (RR, 0.76 [95% CI, 0.67-0.85]) but also with increased procedural MI (RR, 2.48 [95% CI, 1.86-3.31]) with no difference in overall MI (RR, 0.93 [95% CI, 0.83-1.03]). A significant reduction in unstable angina (RR, 0.64 [95% CI, 0.45-0.92]) and increase in freedom from angina (RR, 1.10 [95% CI, 1.05-1.15]) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. CONCLUSIONS: In patients with stable ischemic heart disease, routine revascularization was not associated with improved survival but was associated with a lower risk of nonprocedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these nonfatal spontaneous events improves long-term survival.

Derivation and validation of a clinical model to predict death or cardiac hospitalizations while on the cardiac surgery waitlist.

BACKGROUND: Waitlist management is a global challenge. For patients with severe cardiovascular diseases awaiting cardiac surgery, prolonged wait times are associated with unplanned hospitalizations. To facilitate evidence-based resource allocation, we derived and validated a clinical risk model to predict the composite outcome of death and cardiac hospitalization of patients on the waitlist for cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health care administrative databases, which have information on all Ontario residents. We included patients 18 years or older who waited at home for coronary artery bypass grafting, valvular or thoracic aorta surgeries between 2008 and 2019. The primary outcome was death or an unplanned cardiac hospitalizaton, defined as nonelective admission for heart failure, myocardial infarction, unstable angina or endocarditis. We randomly divided two-thirds of these patients into derivation and one-third into validation data sets. We derived the model using a multivariable Cox proportional hazard model with backward stepwise variable selection. RESULTS: Among 62 375 patients, 41 729 patients were part of the derivation data set and 20 583 were part of the validation data set. Of the total, 3033 (4.9%) died or had an unplanned cardiac hospitalization while waiting for surgery. The area under the curve of our model at 15, 30, 60 and 89 days was 0.85, 0.82, 0.81 and 0.80, respectively, in the derivation cohort and 0.83, 0.80, 0.78 and 0.78, respctively, in the validation cohort. The model calibrated well at all time points. INTERPRETATION: We derived and validated a clinical risk model that provides accurate prediction of the risk of death and unplanned cardiac hospitalization for patients on the cardiac surgery waitlist. Our model could be used for quality benchmarking and data-driven decision support for managing access to cardiac surgery.

A prognostic nomogram for long-term major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

BACKGROUND: Accurate prediction of major adverse cardiovascular events (MACEs) is very important for the management of acute coronary syndrome (ACS) patients. We aimed to construct an effective prognostic nomogram for individualized risk estimates of MACEs for patients with ACS after percutaneous coronary intervention (PCI). METHODS: This was a prospective study of patients with ACS after PCI from January 2013 to July 2019 (n = 2465). After removing patients with incomplete clinical information, a total of 1986 patients were randomly divided into evaluation (n = 1324) and validation (n = 662) groups. Predictors included in the nomogram were determined by a multivariate Cox proportional hazards regression model based on the training set. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the discrimination and predictive accuracy of the nomogram, which were then compared with those of the classic models. The clinical utility of the nomogram was assessed by X-tile analysis and Kaplan-Meier curve analysis. RESULTS: Independent prognostic factors, including lactate level, age, left anterior descending branch stenosis, right coronary artery stenosis, brain natriuretic peptide level, and left ventricular ejection fraction, were determined and contained in the nomogram. The nomogram achieved good areas under the ROC curve of 0.712-0.762 in the training set and 0.724-0.818 in the validation set and well-fitted calibration curves. In addition, participants could be divided into two risk groups (low and high) according to this model. CONCLUSIONS: A simple-to-use nomogram incorporating lactate level effectively predicted 6-month, 1-year, and 4-year MACE incidence among patients with ACS after PCI.

Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial. METHODS: In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin). RESULTS: In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%; Pnoninferiority=0.0086). Cardiac death occurred in 10 (1.3%) versus 10 patients (1.3%; P value for difference, 1.00), target-vessel myocardial infarction occurred in 18 (2.4%) versus 17 patients (2.3%; P value for difference, 0.87), and target-lesion revascularization occurred in 22 (2.9%) versus 20 patients (2.6%; P value for difference, 0.75) for PF-AES as compared with PP-ZES. Overall, definite or probable stent thrombosis occurred in 1.0%. CONCLUSIONS: PF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02328898.

Three-year outcomes related to coronary stenting; a registry-based real-life population study.

Objectives. Developments in medication and coronary interventions have improved coronary artery disease (CAD) treatment. We studied long-term outcomes in an observational, real-life population of CAD patients undergoing percutaneous coronary intervention (PCI) depending on the presentation and the stent type used. Design and results. Register included 789 consecutive patients undergoing PCI. Follow up period was three years with primary composite outcome (MACE) of all cause -mortality, myocardial infarction and target lesion revascularization. Mean age was 65 ± 11 and 69% were male. New-generation drug-eluting stents (DES-2) were associated with lower adjusted rates of MACE (HR 0.47; 95% CI 0.29-0.77) but not mortality (HR 0.50; 95% CI 0.22-1.14) in comparison to bare-metal stents. Patients with STEMI (14.4%) or NSTEMI (13.7%) had higher crude mortality rates than those with unstable (4.5%) or stable CAD (3.1%; p < .001). The association diminished after adjustments in NSTEMI (HR 2.01; 95% CI 0.88-4.58). Among smokers 45% quitted and 36% achieved recommended cholesterol levels. Conclusions. The overall prognosis was good. Irrespective of comorbidities, NSTEMI was not associated with worse outcome than stable CAD. DES-2 was associated with lower rates of MACE than BMS without affecting mortality rate. Patients succeeded better in smoking cessation than reaching recommended cholesterol levels.

Pathways leading to prevention of fatal and non-fatal cardiovascular disease: An interaction model on 15 years population-based cohort study.

BACKGROUND: A comprehensive study on the interaction of cardiovascular disease (CVD) risk factors is critical to prevent cardiovascular events. The main focus of this study is thus to understand direct and indirect relationships between different CVD risk factors. METHODS: A longitudinal data on adults aged ≥35 years, who were free of CVD at baseline, were used in this study. The endpoints were CVD events, whereas their measurements were demographic, lifestyle components, socio-economics, anthropometric measures, laboratory findings, quality of life status, and psychological factors. A Bayesian structural equation modelling was used to determine the relationships among 21 relevant factors associated with total CVD, stroke, acute coronary syndrome (ACS), and fatal CVDs. RESULTS: In this study, a total of 3161 individuals with complete information were involved in the study. A total of 407 CVD events, with an average age of 54.77(10.66) years, occurred during follow-up. The causal associations between six latent variables were identified in the causal network for fatal and non-fatal CVDs. Lipid profile, with the coefficient of 0.26 (0.01), influenced the occurrence of CVD events as the most critical factor, while it was indirectly mediated through risky behaviours and comorbidities. Lipid profile at baseline was influenced by a wide range of other protective factors, such as quality of life and healthy lifestyle components. CONCLUSIONS: Analysing a causal network of risk factors revealed the flow of information in direct and indirect paths. It also determined predictors and demonstrated the utility of integrating multi-factor data in a complex framework to identify novel preventable pathways to reduce the risk of CVDs.

An Upfront Two-Stent Strategy for True Coronary Bifurcation Lesions with A Large Side Branch in Acute Coronary Syndrome: A Two-Year Follow-Up Study.

Background and Objectives: Little is known about the upfront two-stent strategy (U2SS) for true coronary bifurcation lesions (CBLs) in acute coronary syndrome (ACS). We aimed to present our two-year follow-up results on the U2SS by using different two-stent techniques for the true CBL with a large side branch (SB) in ACS patients, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), and to identify independent predictors of the presence of major adverse cardiac events (MACEs) after intervention. Materials and Methods: The study included 201 consecutive ACS patients with true CBLs who underwent percutaneous coronary intervention (PCI) using U2SS from October 2015 to March 2018. Clinical outcomes at follow-up were assessed. MACE was defined as a composite of cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). Results: 31.3% of the patients had an UA, 46.3% had an NSTEMI, and 22.4% had an STEMI. CBL was most frequently located in the left anterior descending (LAD)/diagonal artery (59.2%). In total, 71.1% of the patients had a Medina classification (1,1,1). Overall, 62.2% of cases were treated with mini-crush stenting. Clopidogrel was given in 23.9% of the patients; 71.1% of the patients received everolimus eluting stent (EES); and 11.9% received a sirolimus eluting stent (SES). Final kissing balloon inflation was carried out in all patients, with an unsatisfactory rate of 5%. A proximal optimization technique sequence was successfully carried out in all patients. The MACE incidence was 16.9% with a median follow-up period of 2.1 years. There were seven cardiac deaths (3.5%). The TLR rate was 13.4% (n = 27), with PCI treatment in 16 patients, and coronary artery bypass grafting treatment in 11 patients. After multivariate penalized logistic regression analysis (Firth logistic regression), clopidogrel use (odds ratio (OR): 2.19; 95% confidence interval (CI): 0.41-2.51; p = 0.007) and SES use (OR: 1.86; 95% CI: 0.31-2.64; p = 0.014) were independent predictors of the presence of MACE. Conclusion: U2SS is feasible and safe for the true CBLs with large and diseased SB in ACS patients, and is related to a relatively low incidence of MACE. Clopidogrel use and SES use may predict the MACE development in ACS patients treated using U2SS.

Validating Utility of Dual Antiplatelet Therapy Score in a Large Pooled Cohort From 3 Japanese Percutaneous Coronary Intervention Studies.

BACKGROUND: The dual antiplatelet therapy (DAPT) score was developed to estimate ischemic and bleeding risks from the DAPT study. However, few studies validated its utility externally. We sought to validate the utility of the DAPT score in the Japanese population. METHODS: In a pooled cohort of 3 studies conducted in Japan (the CREDO-Kyoto [Coronary Revascularization Demonstrating Outcome Study in Kyoto] Registry Cohort-2, RESET [Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial], and NEXT [NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial]), we compared risks for ischemic and bleeding events from 13 to 36 months after percutaneous coronary intervention among patients with a DAPT score ≥2 (high DS) and a DAPT score <2 (low DS). RESULTS: Among 12 223 patients receiving drug-eluting stents who were free from ischemic or bleeding events at 13 months after percutaneous coronary intervention, 3944 patients had high DS and 8279 had low DS. The cumulative incidence of primary ischemic end point (myocardial infarction/stent thrombosis) was significantly higher in high DS than in low DS (1.5% versus 0.9%, P=0.002), whereas the cumulative incidence of primary bleeding end point (GUSTO moderate/severe) tended to be lower in high DS than in low DS (2.1% versus 2.7%, P=0.07). The cumulative incidences of cardiac death, myocardial infarction, and stent thrombosis were also significantly higher in high DS than in low DS (2.0% versus 1.4%, P=0.03; 1.5% versus 0.8%, P=0.002; 0.7% versus 0.3%, P<0.001, respectively), whereas the cumulative incidences of noncardiac death and GUSTO severe bleeding were significantly lower in high DS than in low DS (2.4% versus 3.9%, P<0.001; 1.0% versus 1.6%, P=0.03, respectively). CONCLUSIONS: In the current population, the DAPT score successfully stratified ischemic and bleeding risks, although the ischemic event rate was remarkably low even in high DS. Further studies would be warranted to evaluate the utility of prolonged DAPT guided by the DAPT score.

Simulation of impact on cardiovascular events due to lipid-lowering therapy intensification in a population with atherosclerotic cardiovascular disease.

In patients with atherosclerotic cardiovascular disease (ASCVD), guidelines recommend statins as first-line lipid-lowering therapy (LLT) with addition of nonstatin agents in those with persistently elevated low-density lipoprotein cholesterol levels. METHODS: To estimate the cardiovascular (CV) risk reduction implications of treatment intensification, we used a previously reported simulation model with enhancements. An ASCVD cohort was developed from a US claims database. A Cox model was used to estimate baseline risk of CV events: myocardial infarction, ischemic stroke, unstable angina hospitalization, elective coronary revascularization, or cardiovascular death. Patients were sampled with replacement (bootstrapping) and entered the simulation model, which applied stepwise LLT intensification logic, with a goal of achieving low-density lipoprotein cholesterol less than 70 mg/dL at each step. CV risk reduction assumptions were based on published data. Two treatment intensification scenarios were investigated: ideal and real-world (which accounted for statin intolerance, nonadherence, and payer restrictions). RESULTS: In a cohort of 1,000 patients with ASCVD, approximately 813 (809-818) would require treatment intensification with LLT under an ideal treatment intensification scenario. Before treatment intensification, 183 (179-187) events would be expected to occur over 5 years. With treatment intensification, 40 (34-45) of these events could be avoided. In a real-world scenario, about 818 (813-823) patients require treatment intensification with LLT, resulting in 29 (24-34) events avoided over 5 years. CONCLUSIONS: Intensification of LLT in an ASCVD population translates into a substantial number of CV events avoided. This simulation-based model could assist in assessing the potential benefits of various types of population-level LLT interventions.

One-year clinical performance of ABSORB bioresorbable vascular scaffold in patients presenting with acute coronary syndromes: Results from the RAI registry.

OBJECTIVES: To report 1-year clinical outcomes of bioresorbable vascular scaffold (BVS) in acute coronary syndromes (ACS) population. BACKGROUND: BVS use has rapidly extended to high-risk patients as those presenting with ACS. To date limited data have been reported on BVS performance in ACS patients. METHODS: RAI is a multicenter, prospective registry that included 1,505 patients treated with at least 1 successful BVS implantation. A subgroup analysis on ACS patients was performed and the 1-year outcomes of this cohort compared to the remaining stable coronary artery disease (SCAD) population are reported here. Coprimary endpoints were target-lesion revascularization (TLR) and scaffold thrombosis (ScT) at 1-year follow-up. RESULTS: Fifty-nine percent of the patients presented with ACS, of whom 36.5% with ST-elevation myocardial infarctions. ACS patients were significantly younger, with a better cardiovascular risk profile, a lower rate of multivessel disease, chronic total occlusion or in-stent restenosis and a lower Syntax score. Predilation and postdilation were performed in 97.4% and in 96.5% of cases, respectively. No differences were noted in terms of TIMI 3 final flow, but acute gain was greater in ACS compared to SCAD group (P < 0.001). At one-year follow-up no differences were found in terms of TLR (3.3% vs. 3.3%, P = 0.98), and device-oriented composite end-point (4.3% vs. 3.4%, P = 0.4) between ACS and SCAD groups. The rate of definite/probable ScT was numerically higher in ACS vs. stable CAD patients (1.3% vs. 0.8%, P = 0.2). CONCLUSIONS: Our data suggest that the use of BVS in ACS patients is associated with a numerically higher rate of ScT compared to SCAD population numerically higher, but without statistical significance.

Percutaneous coronary intervention with drug-coated balloon-only strategy in stable coronary artery disease and in acute coronary syndromes: An all-comers registry study.

OBJECTIVES: The aim of this single center all-comers retrospective registry study was to assess the efficacy and safety of percutaneous coronary intervention (PCI) using drug-coated balloon (DCB) in de novo lesions including large proximal coronary arteries. METHODS: A total of 487 PCIs were performed using paclitaxel-coated DCB in 562 de novo lesions with the possibility for bailout stenting in a patient population presenting with stable coronary artery disease (CAD) or acute coronary syndrome (ACS). Half of the patients had at least one risk factor for bleeding. All of the treated lesions were de novo and 60% of DCBs used were ≥ 3.0 mm in diameter. The median follow-up time was 18 months for MACE and 60 months for survival. RESULTS: The total mortality after DBC only strategy was 2.3 and 9.3% at 12 months in stable CAD and ACS, respectively. The 12-month MACE rate was 7.1 and 12% in stable CAD and ACS. The rate of ischemia-driven target lesion revascularization was only 1.4% in stable CAD and 2.8% after ACS at 12 months. Median duration of DAPT was one month. The 12 month rate of significant bleeding (Bleeding Academic Research Consortium types 2-5) was 5.9%. Acute vessel closure occurred only in one case (0.2%) after DCB treatment. Bailout stenting was used in 12% of lesions. CONCLUSIONS: PCI using DCB-only strategy with the possibility for provisional stenting is a safe and efficient in de novo coronary artery lesions in both stable CAD and ACS. This strategy may be useful especially in patients with high bleeding risk.

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain-the WESTCOR study: study design.

Objectives. The main aim of the Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain (WESTCOR-study) (Clinical Trials number NCT02620202) is to improve diagnostic pathways for patients presenting to the Emergency department (ED) with acute chest pain. Design. The WESTCOR-study is a two center, cross-sectional and prospective observational study recruiting unselected patients presenting to the ED with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Patient inclusion started September 2015 and we plan to include 2250 patients, finishing in 2019. The final diagnosis will be adjudicated by two independent cardiologists based on all available information including serial high sensitivity cardiac troponin measurements, coronary angiography, coronary CT angiography and echocardiography. The study includes one derivation cohort (N = 985) that will be used to develop rule out/rule in algorithms for NSTEMI and NSTE-ACS (if possible) using novel troponin assays, and to validate established NSTEMI algorithms, with and without clinical scoring systems. The study further includes one subcohort (n = 500) where all patients are examined with coronary CT angiography independent of biomarker status, aiming to assess the associations between biomarkers and the extent and severity of coronary atherosclerosis. Finally, an external validation cohort (N = 750) will be included at Stavanger University Hospital. Prospective studies will be based on the merged cohorts. Conclusion. The WESTCOR study will provide new diagnostic algorithms for early inclusion and exclusion of NSTE-ACS and insights in the associations between cardiovascular biomarkers, CT-angiographic findings and short and long-term clinical outcomes.

Effect of intensive blood pressure control in patients with type 2 diabetes mellitus over 9 years of follow-up: A subgroup analysis of high-risk ACCORDION trial participants.

Although guidelines recommend strict blood pressure (BP) control in patients with type 2 diabetes mellitus (T2DM) and elevated cardiovascular risk, the long-term effects of this approach are unknown. We investigated the effect of intensive BP control on clinical outcomes in patients with T2DM over 9 years of follow-up. We included Action to Control Cardiovascular Risk in Diabetes - Blood Pressure participants in the standard glucose control arm who had established cardiovascular disease, chronic kidney disease, were ≥75 years of age or who had a 10-year coronary heart risk ≥15%. Participants were randomized to either intensive (systolic BP < 120 mm Hg) or standard (systolic BP < 140 mm Hg) BP control for an average of 5 years. Observational follow-up occurred for an average of 4 years thereafter. After an average total follow-up of 9 years, intensive BP control reduced the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke by 25% (hazard ratio, 0.75; 95% confidence interval, 0.60-0.95; P = .02). The overall benefit was driven by a reduction in nonfatal myocardial infarction (P = .01). In this post-hoc analysis, the benefits of a fixed-duration intensive BP control intervention in patients with T2DM persisted throughout 9 years of follow-up.

Comparative Effectiveness of Routine Invasive Coronary Angiography for Managing Unstable Angina.

BACKGROUND: Non-ST-segment elevation acute coronary syndromes include unstable angina and non-ST-segment elevation myocardial infarction. Most randomized controlled trials of routine versus selective invasive coronary angiography have high rates of crossover from control to intervention groups and do not include subgroup analysis for unstable angina. Consequently, no clear, specific recommendations exist regarding the use of angiography in unstable angina. OBJECTIVE: To assess the effect of angiography on mortality in unstable angina, incorporating the results of additional cardiac procedures and events. DESIGN: Longitudinal study using hospital discharge data, discrete-time survival analysis with propensity score adjustment, and sensitivity analysis. SETTING: Victoria, Australia, 2001 to 2011. PARTICIPANTS: All residents, all ages. INTERVENTION: Routine invasive coronary angiography. MEASUREMENTS: 12-month all-cause mortality. RESULTS: Emergently admitted patients with unstable angina (n = 33 901) who did or did not receive angiography during their first hospitalization were balanced on 44 covariates of propensity score. Routine angiography was associated with a 52% decrease in 12-month mortality (hazard ratio, 0.48 [95% CI, 0.38 to 0.61]); revascularization offered no additional statistical mortality benefit compared with diagnostic angiography alone. The predicted cumulative probability of death at 12 months was 0.024 (CI, 0.021 to 0.027) for patients receiving angiography within 2 months of their index unstable angina versus 0.097 (CI, 0.090 to 0.105) for those not receiving it. Sensitivity analysis demonstrated that to negate the observed effect size, an unmeasured confounder must independently decrease mortality by 90% and have a prevalence gap of 15% or greater between the angiographic groups. LIMITATION: Nonrandom allocation of angiography. CONCLUSION: Patients with unstable angina benefit from an invasive management pathway initiated by invasive coronary angiography during their hospitalization and up to 2 months after discharge. PRIMARY FUNDING SOURCES: National Health and Medical Research Council, Australia and BUPA Health Foundation.

Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial.

AIMS: To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L). METHODS AND RESULTS: The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91). CONCLUSION: Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed. TRIAL NO: UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial.

BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. METHODS: In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. FINDINGS: During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41-0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35-0·76; p=0·0010) for myocardial infarction, 0·19 (0·07-0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25-1·46; p=0·2650) for stroke, and 0·89 (0·62-1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. INTERPRETATION: In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. FUNDING: Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

Impact of an optical coherence tomography guided approach in acute coronary syndromes: A propensity matched analysis from the international FORMIDABLE-CARDIOGROUP IV and USZ registry.

AIM: To determine the potential clinical impact of OCT (Optical Coherence Tomography) during primary percutaneous coronary intervention in patients presenting with ACS (Acute Coronary Syndrome). METHODS AND RESULTS: FORMIDABLE is a multicentre retrospective registry enrolling all patients presenting with ACS and treated with an OCT-guided approach, while the USZ registry enrolled patients treated with a standard angiography guided approach. Multivariate adjustment was performed via a propensity score matching. The number stents useds was the primary outcome, while the incidence of MACE (a composite of death, myocardial infarction, target vessel revascularization, and stent thrombosis) was the secondary endpoint. A total of 285 patients OCT-guided and 1,547 angiography guided patients were enrolled, resulting in 270 for each cohort after propensity score with matching. Two stents were used in 12% versus 34%; 3 stents in 8% versus 38% of the patients (P < 0.001). After a follow up of 700 days (450-890), there was no difference in myocardial infarction (6% vs. 6%, P = 0.86), while MACE (11% vs. 16%, P = 0.06), target vessel revascularization (2% vs. 4%, P = 0.15) and stent thrombosis rates (0% vs. 2.7%, P = 0.26) were numerically lower for the OCT-guided cohort but none of these endpoints did reach statistical significance. CONCLUSIONS: An OCT-guided approach reduced the number of stents used, number of patients treated with more than one stent, while there was no statistically significant difference in clinical endpoints while most of them were numerically lower, including stent thrombosis rates. © 2016 Wiley Periodicals, Inc.

Expanded clinical use of everolimus eluting bioresorbable vascular scaffolds for treatment of coronary artery disease.

BACKGROUND: Limited data are currently available on the performance of everolimus eluting bioresorbable vascular scaffold (BVS) for treatment of complex coronary lesions representative of daily practice. METHODS: This is a prospective, mono-center, single-arm study, reporting data after BVS implantation in patients presenting with stable, unstable angina, or non-ST segment elevation myocardial infarction caused by de novo stenotic lesions in native coronary arteries. No restrictions were applied to lesion complexity. Procedural results and 12-month clinical outcomes were reported. RESULTS: A total of 180 patients have been evaluated in the present study, with 249 treated coronary lesions. Device Success per lesion was 99.2%. A total of 119 calcified lesions were treated. Comparable results were observed among severe, moderate and noncalcified lesions in term of %diameter stenosis (%DS) (20.3 ± 10.5%, 17.8 ± 7.7%, 16.8 ± 8.6%; P = 0.112) and acute gain (1.36 ± 0.41 mm, 1.48 ± 0.44 mm, 1.56 ± 0.54 mm; P = 0.109). In bifurcations (54 lesions), side-branch ballooning after main vessel treatment was often performed (33.3%) with low rate of side-branch impairment (9.3%). A total of 29 cases with coronary total occlusions were treated. After BVS implantation %DS was not different from other lesion types (17.2 ± 9.4%, vs. 17.7 ± 8.6%; P = 0.780). At one year, all-cause mortality was reported in three cases. The rate of target lesion revascularization and target vessel revascularization was 3.3%. The rate of definite scaffold thrombosis was 2.6%. CONCLUSIONS: The implantation of the everolimus eluting bioresorbable vascular scaffold in an expanded range of coronary lesion types and clinical presentations was observed to be feasible with promising angiographic results and mid-term clinical outcomes. © 2016 Wiley Periodicals, Inc.