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Guidelines have lowered blood pressure (BP) targets to130/80 mmHg. We examined the benefit of intensive control for each BP component, versus the burden of other modifiable risk factors, in patients with chronic coronary syndromes (CCS).The CLARIFY registry (ISRCTN43070564) enrolled 32 703 CCS patients, from 2009-2010, with a 5-year follow-up. Patients with either BP component below European guideline safety boundaries (120/70 mmHg) were excluded, leaving 19 167 patients (mean age 63.8 ± 10.1 years, 78% men) in the present analysis. A multivariable-adjusted Cox proportional hazards model showed a gradual increase in cardiovascular risk (cardiovascular death, myocardial infarction, or stroke) when the number of uncontrolled risk factors (active smoking, no physical activity, low-density lipoprotein cholesterol ≥100 mg/dL, and diabetes with glycated haemoglobin ≥7%) increased [adjusted hazard ratio (HR): 1.34; 95% confidence interval (CI): 1.17-1.52, 1.65 (1.40-1.94), and 2.47 (1.90-3.21) for 1, 2, and 3 or 4 uncontrolled risk factors, respectively, versus 0], without significant interaction with BP. Although uncontrolled systolic (≥140 mmHg) and diastolic (≥90 mmHg) BP were both associated with higher risk than standard BP, standard BP was associated with higher risk than optimal control for only the diastolic component (adjusted HR: 1.08; 95% CI: 0.94-1.25 for systolic BP 130-139 versus 120-129 mmHg and 1.43; 95% CI: 1.27-1.62 for diastolic BP 80-89 versus 70-79 mmHg).Our results suggest that optimal BP target in CCS may be ≤139/79 mmHg, and that optimizing the burden of other risk factors should be prioritized over further reduction of systolic BP.We aimed to compare the benefit associated with strict versus standard control of blood pressure with the potential benefit of controlling other modifiable risk factors in patients with chronic coronary syndromes. Our analysis conducted in nearly 20 000 patients from the CLARIFY registry (a prospective international cohort of patients with chronic coronary syndromes) showed that the benefit associated with strict BP control (BP 130/80 mmHg) was marginal and only driven by the diastolic component of blood pressure, whereas having one or more uncontrolled other risk factors was associated with a gradually increasing risk, for all underlying BP levelsPatients with CCS should be treated to achieve BP140/80 mmHg. However, our results suggest that optimizing the burden of other risk factors (lipid-lowering therapy, exercise, smoking cessation, diabetes control) may need to be prioritized before considering further reduction of systolic BP.

Background High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. Methods In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. Results Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. Conclusions Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.)

Background: Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization. Methods: Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis. Results: Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 [95% CI, 1.12−1.55] for persistence of angina; adjusted hazard ratio, 1.37 [95% CI, 1.11−1.70] for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 [95% CI, 0.82−1.15]). Conclusions: Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease. Registration: URL: https://www.isrctn.com ; Unique identifier: ISRCTN43070564.

Left Bundle Branch Block (LBBB) is a frequently encountered electrical abnormality in patients with chronic (more than 3 months after myocardial infarction, or evidence of coronary artery disease with ischemia) coronary syndromes (CCS), but its prognostic significance remains unclear. We aimed to describe the prevalence, incidence and five-year outcomes of LBBB in outpatients with CCS using the CLARIFY registry. Main outcome was a composite of CV death, MI or stroke. Secondary outcomes included all cause death, hospitalization for heart failure (HF) and permanent pacemaker implantation. Among 23.544 patients with available information regarding LBBB status at baseline, 1.041 (4.4%) had LBBB at baseline and 1.015 (4.5%) patients developed a new LBBB during 5-year follow-up. In multivariate analysis, LBBB at baseline was not associated with the composite outcome of CV death, MI or stroke (HR 1.06, 95% CI [0.86 - 1.31], p = 0.67) or the risk of all-cause death (HR 1.07, 95% CI [0.87 - 1.32], p = 0.52) but was significantly associated with a higher risk of hospitalization for HF (HR 1.50, 95% CI [1.21 - 1.88], p0.001) and permanent pacemaker implantation (HR 2.11, 95% CI [1.45 - 3.07], p0.001). The main factors associated with new-onset LBBB were male sex (HR 0.8 [0.66-0.98], p = 0.028) history of atrial fibrillation (HR 1.29, 95% CI [1.01 - 1.64], p = 0.04), CABG (HR 1.27, [1.08 - 1.51], p = 0.004) and MI (HR 1.19, 95% CI [1.01 - 1.40], p = 0.034). In conclusion, in a contemporary registry of outpatients with CCS, the prevalence of LBBB was 4.4% and the additional 5-years incidence 6.2%. LBBB, in itself, was not associated with a higher risk of major adverse cardiovascular events or all cause mortality. It was however an independent predictor of risk of hospitalization for heart failure and permanent pacemaker implantation.

Background:\ud \ud The COMPASS trial showed a reduction of ischemic events with low-dose rivaroxaban and aspirin in chronic coronary syndromes (CCS) compared with aspirin alone, at the expense of increased bleeding.\ud \ud Hypothesis:\ud \ud The CHA DS VaSc Score, REACH Recurrent Ischemic (RIS), and REACH Bleeding Risk Score (BRS) could identify patients with a favorable trade-off between ischemic and bleeding events, among COMPASS-eligible patients.\ud \ud Methods\ud \ud We identified the COMPASS-eligible population within the CLARIFY registry (>30.000 patients with CCS). High-bleeding risk patients (REACH BRS > 10) were excluded, as in the COMPASS trial. Patients were categorized as low (0-1) or high (≥ 2) CHA DS VaSc; low (0-12) or intermediate (13-19) REACH RIS, and low (0-6) or intermediate (7-10) REACH BRS. Ischemic outcome was the composite of cardiovascular death, myocardial infarction or stroke. Bleeding was defined as serious bleeding (haemorrhagic stroke, hospitalization for bleeding, transfusion).\ud \ud Results:\ud \ud The COMPASS-eligible population comprised 5.142 patients with ischemic and bleeding outcome of 2.3 (2.1-2.5) and 0.5 (0.4-0.6) per 100 patient-years, respectively. Patients with intermediate REACH RIS (n = 1934 [37.6%]) had the higher ischemic risk (3.0 [2.6-3.4]) with similar bleeding risk (0.5 [0.4-0.7]) as the overall population. Patients with low CHA DS VaSc (n = 229 [4.4%]) had a very low ischemic risk (0.6 [0.3-1.3]) with similar bleeding risk (0.5 [0.2-1.1]).\ud \ud Conclusions:\ud \ud Intermediate REACH RIS identified potential optimal candidates for adjunction of low-dose rivaroxaban while patients with low CHA DS VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding.

Aims The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. Methods and results We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009–2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84–1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79–1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91–1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50–0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37–0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52–0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality. Conclusion In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI.

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Introduction Cell therapy has the potential to improve symptoms and clinical outcomes in refractory angina (RFA). Further analyses are needed to evaluate factors influencing its therapeutic effectiveness. Aim Assessment of electromechanical (EM) parameters of the left ventricle (LV) and investigation of correlation between EM parameters of the myocardium and response to CD133+ cell therapy. Material and methods Thirty patients with RFA (16 active and 14 placebo individuals) enrolled in the REGENT-VSEL trial underwent EM evaluation of the LV with intracardiac mapping system. The following parameters were analyzed: unipolar voltage (UV), bipolar voltage (BV), local linear shortening (LLS). Myocardial ischemia was evaluated with single-photon emission computed tomography (SPECT). The median value of each EM parameter was used for intra-group comparisons. Results Global EM parameters (UV, BV, LLS) of LV in active and placebo groups were 11.28 mV, 3.58 mV, 11.12%, respectively; 13.00 mV, 3.81 mV, 11.32%, respectively. EM characteristics analyzed at global and segmental levels did not predict response to CD133+ cell therapy in patients with RFA (Global UV, BV and LLS at rest R = –0.06; R = 0.2; R = –0.1 and at stress: R = 0.07, R = 0.09, R = –0.1, respectively; Segmental UV, BV, LLS at rest R = –0.2, R = 0.03, R = –0.4 and at stress R = 0.02, R = 0.2, R = –0.2, respectively). Multiple linear regression of the treated segments showed that only pre-injection SPECT levels were significantly correlated with post-injection SPECT, either at rest or stress (p < 0.05). Conclusions Electromechanical characteristics of the left ventricle do not predict changes of myocardial perfusion by SPECT after cell therapy. Baseline SPECT results are only predictors of changes of myocardial ischemia observed at 4-month follow-up.

No abstract available.

Aims This study aims to explore long‐term clinical outcomes of cardiopoiesis‐guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial. Methods and results CHART‐1 is a multinational, randomized, and double‐blind trial conducted in 39 centres in heart failure patients (n = 315) on standard‐of‐care therapy. The ‘active’ group received cardiopoietic stem cells delivered intramyocardially using a retention‐enhanced catheter. The ‘control’ group underwent patient‐level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow‐up, patients with left ventricular end‐diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years. Conclusions Longitudinal follow‐up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long‐term clinical follow‐up thus offers guidance for future targeted trials.

UNSTRUCTURED Artificial intelligence–driven voice technology deployed on mobile phones and smart speakers has the potential to improve patient management and organizational workflow. Voice chatbots have been already implemented in health care–leveraging innovative telehealth solutions during the COVID-19 pandemic. They allow for automatic acute care triaging and chronic disease management, including remote monitoring, preventive care, patient intake, and referral assistance. This paper focuses on the current clinical needs and applications of artificial intelligence–driven voice chatbots to drive operational effectiveness and improve patient experience and outcomes.

Summary Background Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI. Methods We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21–85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89). Findings From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receive either trimetazidine (n=2998) or placebo (n=3009). After a median follow-up of 47·5 months (IQR 42·3–53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88–1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. Similar results were obtained when patients were categorised according to whether they had an elective or urgent PCI. 1219 (40·9%) of 2983 patients in the trimetazidine group and 1230 (41·1%) of 2990 patients in the placebo group had serious treatment-emergent adverse events. Frequencies of adverse events of interest were similar between the groups. Interpretation Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. However, the long-term prescription of this treatment does not appear to be associated with any statistically significant safety concerns in the population studied. Funding Servier.

Aims The European Society of Cardiology (ESC) European Observational Research Programme (EORP) Cardiomyopathy Registry is a prospective multinational registry of consecutive patients with cardiomyopathies. The objective of this report is to describe the short-term outcomes of adult patients (≥18 years old). Methods and results Out of 3208 patients recruited, follow-up data at 1 year were obtained in 2713 patients (84.6%) [1420 with hypertrophic (HCM); 1105 dilated (DCM); 128 arrhythmogenic right ventricular (ARVC); and 60 restrictive (RCM) cardiomyopathies]. Improvement of symptoms (dyspnoea, chest pain, and palpitations) was globally observed over time (P Conclusions Despite symptomatic improvement, patients with cardiomyopathies remain prone to major clinical events in the short term. Outcomes were different not only according to cardiomyopathy subtypes but also in relatives vs. index patients, and according to European regions.

Background Non-contrast-enhanced cardiac computed tomography (NCE-CCT) is currently used for coronary artery calcium (CAC) scoring. Meanwhile, other cardiac, vascular and extra-cardiac structures can be evaluated. Data about ascending aorta (AA) and left atrium (LA) has been quantified separately in a few studies. Their mutual proportion has not been examined, as yet. Aim. We hypothesize that mutual proportion between AA and LA size might help for diagnosing their enlargement before absolute cut-off values are reached. Method Among 7950 patients who had NCE-CCT with a 64 raw scanner (Aquillion, Toshiba) within the last decade in our center, in 797 persons the AA diameter (at the level of pulmonary artery bifurcation) and LA diameter and area (highest value) were measured. Raw AAD values were qualified as abnormal if exceeded upper normal limit UNL) for age and height. Weight, BMI and BSA has not been used in order to avoid falsified results in obese patients. The ratio AAD:LAD was quantified as low (1.2). Results There were 45 patients (5.6%) who had AAD higher than age-height predicted UNL, including 24 patients with a raw AAD >43mm (3.0%). The other 752 has their AAD within limits. The means of AAD were 42.9 ± 3.2mm and 33.6 ± 3.6mm (p 1.2 in 845 subjects might suggest increased AAD in spite to normal raw diameter. Similar rules were found in respect to the LA area. Conclusions Ascending aorta and left atrium enlargement are infrequently recognized in patients referred to CAC scoring. Mutual proportion between AA and LA size might complement diagnostic approach of their abnormalities.

International audience; Aims: Cardiomyopathies are a heterogeneous group of disorders that increase the risk for atrial fibrillation (AF). The aim of the study is to assess the prevalence of AF, anticoagulation management, and risk of stroke/transient ischaemic attack (TIA) in patients with cardiomyopathy.Methods and results: Three thousand two hundred eight consecutive adult patients with cardiomyopathy (34.9% female; median age: 55.0 years) were prospectively enrolled as part of the EURObservational Research Programme Cardiomyopathy/Myocarditis Registry. At baseline, 903 (28.2%) patients had AF (29.4% dilated, 27.5% hypertrophic, 51.5% restrictive, and 14.7% arrhythmogenic right ventricular cardiomyopathy, P < 0.001). AF was associated with more advanced New York Heart Association class (P < 0.001), increased prevalence of cardiovascular risk factors and co-morbidities, and a history of stroke/TIA (P < 0.001). Oral anticoagulation was administered in 71.7% of patients with AF (vitamin K antagonist: 51.6%; direct oral anticoagulant: 20.1%). At 1 year follow-up, the incidence of cardiovascular endpoints was as follows: stroke/TIA 1.85% (AF vs. non-AF: 3.17% vs. 1.19%, P < 0.001), death from any cause 3.43% (AF vs. non-AF: 5.39% vs. 2.50%, P < 0.001), and death from heart failure 1.67% (AF vs. non-AF: 2.44% vs. 1.31%, P = 0.033). The independent predictors for stroke/TIA were as follows: AF [odds ratio (OR) 2.812, P = 0.005], history of stroke (OR 7.311, P = 0.010), and anaemia (OR 3.119, P = 0.006).Conclusions: The study reveals a high prevalence and diverse distribution of AF in patients with cardiomyopathies, inadequate anticoagulation regimen, and high risk of stroke/TIA in this population.

Aims The aims of this study were to ascertain the relationship between level of physical activity and outcomes and to discriminate the determinants of physical activity performance or avoidance. Methods CLARIFY is an international prospective registry of 32,370 consecutive outpatients with stable coronary artery disease who were followed for up to five years. Patients were grouped according to the level and frequency of physical activity: i) sedentary ( n = 5223; 16.1%); ii) only light physical activity most weeks (light; n = 16,634; 51.4%); iii) vigorous physical activity once or twice per week (vigorous ≤ 2×; n = 5427; 16.8%); iv) vigorous physical activity three or more times per week (vigorous >2×; n = 5086; 15.7%). The primary outcome was the composite of cardiovascular death, myocardial infarction and stroke. Results Patients performing vigorous physical activity ≤2 × had the lowest risk of the primary outcome (hazard ratio, 0.82; 95% confidence interval, 0.71–0.93; p = 0.0031) taking the light group as reference. Engaging in more frequent exercise did not result in further outcome benefit. All-cause death, cardiovascular death, and stroke occurred less frequently in patients performing vigorous physical activity ≤2×. However, the rate of myocardial infarction was comparable between the four physical activity groups. Female sex, peripheral artery disease, diabetes, previous myocardial infarction or stroke, pulmonary disease and body mass index all emerged as independent predictors of lower physical activity. Conclusion Vigorous physical activity once or twice per week was associated with superior cardiac outcomes compared with patients performing no or a low level of physical activity in outpatients with stable coronary artery disease.

Chronic kidney disease (CKD) is associated with an increased cardiovascular risk in a broad spectrum of populations. However, the risk associated with a reduced estimated glomerular filtration rate (eGFR) in patients with stable coronary artery disease receiving standard care in the modern era, independently of baseline cardiovascular disease, risk factors, and comorbidities, remains unclear. We analyzed data from 21,911 patients with stable coronary artery disease, enrolled in 45 countries between November 2009 and July 2010 in the CLARIFY registry. Patients with abnormal renal function were older, with more comorbidities, and received slightly lower&mdash, although overall high&mdash, rates of evidence-based secondary prevention therapies than patients with normal renal function. The event rate of patients with CKD stage 3b or more (eGFR &lt, 45 mL/min/1.73 m2) was much higher than that associated with any comorbid condition. In a multivariable adjusted Cox proportional hazards model, lower eGFR was independently associated with a graded increased risk of cardiovascular mortality, with adjusted HRs (95% CI) of 0.98 (0.81&ndash, 1.18), 1.31 (1.05&ndash, 1.63), 1.77 (1.38&ndash, 2.27), and 3.12 (2.25&ndash, 4.33) for eGFR 60&ndash, 89, 45&ndash, 59, 30&ndash, 44, and &lt, 30 mL/min/1.73 m2, compared with eGFR &ge, 90 mL/min/1.73 m2. A strong graded independent relationship exists between the degree of CKD and cardiovascular mortality in this large cohort of patients with chronic coronary artery disease, despite high rates of secondary prevention therapies. Among clinical risk factors and comorbid conditions, CKD stage 3b or more is associated with the highest cardiovascular mortality.

Aims Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the ‘smoker’s paradox’ suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. Methods The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. Results Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p Conclusion In contrast to the ‘smoker’s paradox’, current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

AIM The contemporary incidence of heart failure (HF) in patients with chronic coronary syndrome is unclear. We aimed to study the incidence and predictors of cardiovascular (CV) death, HF hospitalization or new-onset HF not requiring hospitalization, in patients included in the CLARIFY registry. METHODS AND RESULTS CLARIFY is a contemporary, international registry of ambulatory patients with chronic coronary artery disease, conducted in 45 countries. At baseline, data on demographics, ethnicity, CV risk factors, medical history, cardiac parameters and medication were collected. Patients were followed up yearly up to 5 years. In this analysis, 26 769 patients with no HF history were included. At 5-year follow-up, 4393 patients (16.4%) reached the primary endpoint comprising CV death, HF hospitalization, or new-onset HF. Only 16.7% of them (n = 732) required hospitalization for HF. All-cause death occurred in 6.6% of patients (61.4% were CV). Age over 70 years, left ventricular ejection fraction

Aims: \ud The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline on high blood pressure (BP) lowered the threshold defining hypertension and BP target in high-risk patients to 130/80 mmHg. Patients with coronary artery disease and systolic BP 130–139 mmHg or diastolic BP 80–89 mmHg should now receive medication to achieve this target. We aimed to investigate the relationship between BP and cardiovascular events in ‘real-life’ patients with coronary artery disease considered as having normal BP until the recent guideline.\ud \ud Methods and results: \ud Data from 5956 patients with stable coronary artery disease, no history of hypertension or heart failure, and average BP

Aims Risk estimation is important to motivate patients to adhere to treatment and to identify those in whom additional treatments may be warranted and expensive treatments might be most cost effective. Our aim was to develop a simple risk model based on readily available risk factors for patients with stable coronary artery disease (CAD). Methods and results Models were developed in the CLARIFY registry of patients with stable CAD, first incorporating only simple clinical variables and then with the inclusion of assessments of left ventricular function, estimated glomerular filtration rate, and haemoglobin levels. The outcome of cardiovascular death over ∼5 years was analysed using a Cox proportional hazards model. Calibration of the models was assessed in an external study, the CORONOR registry of patients with stable coronary disease. We provide formulae for calculation of the risk score and simple integer points-based versions of the scores with associated look-up risk tables. Only the models based on simple clinical variables provided both good c-statistics (0.74 in CLARIFY and 0.80 or over in CORONOR), with no lack of calibration in the external dataset. Conclusion Our preferred model based on 10 readily available variables [age, diabetes, smoking, heart failure (HF) symptom status and histories of atrial fibrillation or flutter, myocardial infarction, peripheral arterial disease, stroke, percutaneous coronary intervention, and hospitalization for HF] had good discriminatory power and fitted well in an external dataset. Study registration The CLARIFY registry is registered in the ISRCTN registry of clinical trials (ISRCTN43070564).

[2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)]

Artificial intelligence–driven voice technology deployed on mobile phones and smart speakers has the potential to improve patient management and organizational workflow. Voice chatbots have been already implemented in health care–leveraging innovative telehealth solutions during the COVID-19 pandemic. They allow for automatic acute care triaging and chronic disease management, including remote monitoring, preventive care, patient intake, and referral assistance. This paper focuses on the current clinical needs and applications of artificial intelligence–driven voice chatbots to drive operational effectiveness and improve patient experience and outcomes.

Over the past 13 years bone marrow-derived mononuclear cells (BM-MNCs) have been widely investigated for clinical efficacy in patients following acute myocardial infarction (AMI). These early phase II trials have used various surrogate markers to judge efficacy and, although promising, the results have been inconsistent. The phase III BAMI trial has therefore been designed to demonstrate that intracoronary infusion of BM-MNCs is safe and will significantly reduce the time to first occurrence of all-cause death in patients with reduced left ventricular ejection fraction after successful reperfusion for ST-elevation AMI (powered with the aim of detecting a 25% reduction in all-cause mortality). This is a multinational, multicentre, randomized, open-label, controlled, parallel-group phase III study aiming to enrol approximately 3000 patients in 11 European countries with at least 17 sites. Eligible patients who have impaired left ventricular ejection (≤45%) following successful reperfusion for AMI will be randomized to treatment or control group in a 1:1 ratio. The treatment group will receive intracoronary infusion of BM-MNCs 2–8 days after successful reperfusion for AMI added on top of optimal standard of care. The control group will receive optimal standard of care. The primary endpoint is time from randomization to all-cause death. The BAMI trial is pivotal and the largest trial to date of BM-MNCs in patients with impaired left ventricular function following AMI. The aim of the trial is to provide a definitive answer as to whether BM-MNCs reduce all-cause mortality in this group of patients.

Background: Despite major advances in prevention and treatment, coronary artery disease (CAD) remains the leading cause of death worldwide. Whereas many sources of data are available on the epidemiology of acute coronary syndromes, fewer datasets reflect the contemporary management and outcomes of stable CAD patients. Hypothesis: A worldwide contemporary registry would improve our knowledge about stable CAD. The main objectives are to describe the demographics, clinical profile, contemporary management and outcomes of outpatients with stable CAD; to identify gaps between evidence and treatment; and to investigate long-term prognostic determinants. Methods: CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an ongoing international observational longitudinal registry. Stable CAD patients from 45 countries in Europe, Asia, America, Middle East, Australia and Africa were enrolled between November 2009 and June 2010. The inclusion criteria were previous myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia or prior revascularization procedure. The main exclusion criteria were serious non-cardiovascular disease, conditions interfering with life expectancy or severe other cardiovascular disease (including advanced heart failure). Follow-up visits were planned annually for up to 5 years, interspersed with 6-month telephone calls. Results: Of the 32,703 patients enrolled, most (77.6%) were male, age (mean ± SD) was 64.2 ± 10.5 years, and 71.0% were receiving treatment for hypertension; mean ± SD resting heart rate was 68.2 ± 10.6 bpm. Patients were enrolled based on a history of myocardial infarction >3 months earlier (57.7%), having at least one stenosis >50% on coronary angiography (61.1%), proven symptomatic myocardial ischemia on non-invasive testing (23.1%), or history of percutaneous coronary intervention or coronary artery bypass graft (69.8%). Baseline characteristics were similar across the four subgroups identified by the four inclusion criteria. Conclusion: CLARIFY will provide a useful resource for understanding the current epidemiology of stable CAD.

Rationale : New therapies for refractory angina are needed. Objective : Assessment of transendocardial delivery of bone marrow CD133 + cells in patients with refractory angina. Methods and Results : Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P =0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P =0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P =0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P =0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P =0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P =0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P =0.68), 4 (50% versus 33.3%; P =0.63), 6 (70% versus 50.0%; P =0.42), and 12 months (55.6% versus 81.8%; P =0.33) and use of nitrates after 12 months. Conclusion : Transendocardial CD133 + cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01660581.

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

Background The prevalence, and prognostic implication of left bundle branch block (LBBB) patients with stable coronary artery disease (CAD) is unknown. Purpose To describe the prevalence, incidence and prognostic implications of LBBB in patients with stable CAD. Methods CLARIFY is an international registry of more than 30.000 patients with stable CAD. LBBB was defined as a QRS complex > 120 milliseconds. Patients with previous pacemaker implantation or defibrillator were excluded. The primary outcome was a composite of cardiovascular (CV) Death, MI or stroke, and secondary outcomes included hospitalization for heart failure (HF) or the need for pacemaker implantation. Results From the 23.457 patients with available data, 1.041 (4.4%) had LBBB at baseline and 1.237 (5.3%) during 5-year follow-up. Only 21 patients with newly diagnosed LBBB overtime, had a documented MI the same year. Compared to patients without LBBB, patients with LBBB had a higher risk profile regarding age (67.2 ± 10.1 versus 63.6 ± 10.4 years, P Table 1 , Fig. 1 ). Conclusion The prevalence of LBBB in patients with stable CAD was 4.4% and 5.3% with 5-year follow-up. The majority of newly diagnosed LBBB were not contemporary of myocardial infarction. LBBB was not associated with a higher rate of major adverse cardiovascular events, but with a higher risk of pacemaker implantation and hospitalization for heart failure. This is the first study reporting such results in a broad population of stable CAD patients.

Aims Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants. Methods and results Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7–8.3] overall [male 8.1% (7.8–8.5); female 7.6% (7.0–8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9–12.9) vs. 8.2% (95% CI 7.8–8.7) in patients with no angina, P 0.99. Prescription rates of evidence-based secondary prevention therapies were high. Conclusion This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment. Clinical registry ISRCTN43070564

Background and Aims: Heart failure (HF) is a deadly complication of type 2 diabetes but little is known about its incidence in patients with coronary heart disease (CHD) and impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify baseline variables predictive of incident hospitalization for HF (hHF) or HF-death during median 5.0 years follow-up in this Chinese population with CHD and IGT. Methods: Independent predictors of hHF/HF-death were determined using a Cox proportional hazards model. Patients were censored at first hHF event, HF-death or end of follow-up. The 16 variables tested included age, gender, BMI, smoking, plasma creatinine, prior cardiovascular events, fasting and 2-hour postload glucose and HbA1c. Those with a univariate hHF association (P Results: Of the 6522 ACE participants, 6278 had no prior HF. They were mean (SD) 64.2 (8.0) years old, BMI 25.4 (3.1) kg/m2 and 73% were male. Of these, 111 (1.8%) had ≥1 episode of adjudicated hHF. Significant independent hHF/HF-death predictors were age, plasma creatinine, prior myocardial infarction (MI) and prior atrial fibrillation (AF) (Table). Conclusion: In Chinese patients with CHD and IGT, those at higher risk of hHF/HF-death were older with higher plasma creatinine values, prior MI and prior AF. Disclosure C.A.B. Scott: None. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Amgen Inc., AstraZeneca, Bayer AG, Bayer AG, Bristol-Myers Squibb Company, DalCor Pharmaceuticals, GlaxoSmithKline plc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Theracos, Inc., Vifor Pharma. L. Rydén: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker's Bureau; Self; Bayer AG. Other Relationship; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Y. Sun: None. M. Tendera: Consultant; Self; Bayer AG, Servier. R.L. Coleman: None. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.

INTRODUCTION An international registry of ambulatory patients with stable coronary artery disease (CLARIFY) allows a comparison of management and outcomes in real‑life setting. OBJECTIVES We aimed to compare the management strategies and 5‑year outcomes in patients from Poland and from other European countries. PATIENTS AND METHODS Stable coronary artery disease was defined as previous myocardial infarction (MI) or revascularization, coronary stenosis greater than 50%, or documented symptomatic myocardial ischemia. Patients were followed on an annual basis for 5 years. RESULTS Among the total of 32 703 patients, 1000 were enrolled in Poland, and 17 326 in other European countries. Polish patients were younger, with a higher proportion of women, smokers, and patients with previous MI, dyslipidemia, and hypertension. Patients in both cohorts received adequate medical treatment, with more Polish patients receiving β‑blockers. Blood pressure and lipid control to target was similar and remained low in both cohorts. Diabetes control and successful smoking cessation rates were lower in Poland than in other European countries. Polish patients more often underwent percutaneous coronary intervention. All‑cause (8.5% vs 7.9%; P = 0.81) and cardiovascular death rates (5.3% vs 4.9%; P = 0.82) did not differ between the groups, but fatal or nonfatal MI occurred more often in the Polish cohort (5% vs 3.1%; P = 0.006). Angina control was better in Poland than in other European countries (Canadian Cardiovascular Society class II-IV, 11.5% vs 15.8% of patients; P

ObjectiveTo evaluate cardiovascular (CV) outcomes in outpatients with coronary artery disease (CAD) living alone compared with those living with others.MethodsThe prospeCtive observational LongitudinAl RegIstry oF patients with stable coronarY artery disease (CLARIFY) included outpatients with stable CAD. CLARIFY enrolled participants in 45 countries from November 2009 to July 2010, with 5 years of follow-up. Living arrangement was documented at baseline. The primary outcome was a composite of major adverse cardiovascular events (MACEs) defined as CV death, myocardial infarction (MI) and stroke.ResultsAmong 32 367 patients, 3648 patients were living alone (11.3%). After multivariate adjustment, there were no residual differences in MACE among patients living alone compared with those living with others (HR 1.04, 95% CI 0.92 to 1.18, p=0.52); however, there was significant heterogeneity in the exposure effect by sex (Pinteractioninteraction=0.006). There was no effect modification for MACE by age group (Pinteraction=0.3), although potential varying effects by age for MI (Pinteraction=0.046) and stroke (Pinteraction=0.05).ConclusionsLiving alone was not associated with an independent increase in MACE, although significant sex-based differences were apparent. Men living alone may have a worse prognosis from CV disease than women; further analyses are needed to elucidate the mechanisms underlying this difference.Trial registration numberISRCTN43070564.

Epidemiological studies suggest that both moderate and severe hypertriglyceridemia are associated with increased long term cardiovascular risk and mortality. Interestingly, the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention (REDUCE-IT) randomized trial recently enrolled 8179 statin-treated patients with elevated triglycerides levels (135mg/dL and

Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for the reduction of cardiovascular death, myocardial infarction, and stroke in stable patients with prior atherothrombosis, who have not had a prior stroke or transient ischemic attack. The aims of this study were to investigate: 1) the role of vorapaxar in patients with severe coronary artery disease treated previously with coronary artery bypass grafting (CABG); and 2) safety in patients undergoing CABG while receiving vorapaxar.TRA 2°P-TIMI 50 was a randomized, double-blinded, placebo-controlled trial of vorapaxar in 26,449 stable patients with prior atherothrombosis followed for a median of 30 months. We 1) investigated the efficacy of vorapaxar among patients with a history of CABG prior to randomization ( n=2942); and 2) assessed the safety among 367 patients who underwent a new CABG during the trial.Patients with a prior CABG were at higher risk for cardiovascular death, myocardial infarction, or stroke at three years compared with patients without a prior CABG (13.7% vs. 7.8%, p0.001). Among patients with a prior CABG, vorapaxar significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke (11.9% vs. 15.6%, hazard ratio 0.71, 95% confidence interval 0.58-0.88, p=0.001; number-needed-to-treat = 27). In patients undergoing CABG while receiving vorapaxar, the rate of Thrombolysis in Myocardial Infarction CABG major bleeding was 6.3% vs. 4.1% with placebo (hazard ratio 1.53, 95% confidence interval 0.58-4.01, p=0.39).In patients with a prior CABG, vorapaxar significantly reduced the risk of recurrent major cardiovascular events. In patients undergoing CABG while receiving vorapaxar, bleeding risk appeared similar to that seen in the overall trial population.

Background: Clinical studies have suggested increased risk of thrombotic events after planned cessation of clopidogrel therapy, due to increased platelet reactivity (platelet rebound); however, in many studies platelet function was not assessed before introducing clopidogrel. Patients who are scheduled to stop clopidogrel therapy, do it abruptly, so a gradual drug cessation might provide a beneficial treatment strategy. Aim: To determine whether a clopidogrel discontinuation results in platelet rebound hyperaggregability with increased activity compared to pre-treatment values and to assess whether abrupt or tapering clopidogrel cessation may affect platelet reactivity. Methods: Patients with stable coronary artery disease (n = 49), on chronic acetylsalicylic acid treatment, who underwent coronary angiography, and were scheduled for elective percutaneous coronary intervention with stent implantation were en­rolled. Patients were randomised to either a tapering clopidogrel discontinuation during a two-week period (tapering group, n = 25) or abrupt drug cessation (abrupt group, n = 24). After 12 months of dual antiplatelet therapy with clopidogrel and acetylsalicylic acid, we performed three follow-up visits with blood sampling. Platelet aggregation was assessed using a mul­tiple electrode aggregometer at inclusion, at cessation day, and seven and 14 days after complete clopidogrel discontinuation. The primary endpoint was the level of adenosine-diphosphate (ADP)-induced platelet aggregation. We also analysed platelet function in the ASPI test and platelet count as secondary endpoints. Results: In 36 patients included in the main analysis, we found significant differences between the two study groups in the levels of ADP-induced platelet aggregation at days seven and 14 after cessation of clopidogrel (p = 0.004 and p = 0.04, respectively). In the abrupt group, platelet aggregation returned to the values similar to baseline at day seven. There were no significant differences between baseline, seven, and 14 days after drug cessation (p = 0.92 and p = 0.37, respectively). However, in the tapering group, ADP values at seven and 14 days after drug cessation were significantly decreased, comparing to baseline (p < 0.0001 and p = 0.009, respectively). For the ASPI test and platelet count we did not find significant differ­ences between the groups. All values returned to levels similar to the baseline. During the follow-up there were no serious cardiovascular events or bleedings. Conclusions: Tapering vs. abrupt discontinuation of clopidogrel treatment results in significantly lower platelet aggregation values after 14 days from complete drug cessation. We found no evidence of a platelet rebound effect.

Introduction Paravalvular leak (PVL) related to a surgical prosthetic valve may be associated with clinically significant hemolysis. The influence of transcatheter PVL closure (TPVLC) on hemolysis remains uncertain. Material and methods The prospective registry included patients undergoing TPVLC due to PVL-related heart failure and/or hemolysis. Procedural data, laboratory markers of hemolysis and heart failure status were recorded at baseline, discharge and at 1- and 6-month follow-up. Results Of 116 patients from all those qualified for TPVLC, 79 fulfilled the inclusion/exclusion criteria. Hemolysis was significantly more frequent in patients with mitral location of PVL and with calcifications in its channel. After TPVLC prompt reduction of lactate dehydrogenase activity (617.0 (342.0–899.0) vs. 397 (310.0–480.5) IU/l, p < 0.05) and gradual resolution of anemia (hemoglobin (HGB) 11.7 (10.4–13.8) vs. 13.4 (12.9–13.8) g%, p < 0.05) over 6 months were noted. Effective closure of PVL (> 90% reduction of PVL cross-sectional area) resulted in a more prominent increase of red blood cell count and HGB than in patients with residual regurgitation. The TPVLC-related exacerbation of hemolysis was recorded in 14 patients. Its risk was aggravated by presence of significant hemolysis at baseline or residual flow either by a partially uncovered channel or across the occluder. Reduction of hemolysis after successful TPVLC was sustained in 6-month follow-up. Conclusions Risk factors for PVL-related hemolysis were the presence of calcifications in the defect and mitral location of PVL. The TPVLC effectively reduced hemolysis if at least 90% reduction of PVL cross sectional area was achieved. The effect was sustained in 6-month follow-up. Incomplete closure of PVL may increase the magnitude of hemolysis after TPVLC, but it occurred rarely.

Aims Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Methods Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (

Background The COMPASS trial demonstrated efficacy of combination of aspirin and low dose rivaroxaban, compared to aspirin alone, but at the expense of increased bleeding. Purpose To evaluate the performance of the CHA2DS2VaSc (0–9), the REACH Recurrent Ischemic Score (RIS) (0–29) and the REACH Bleeding Risk Score (BRS) (0–22) to identify patients with the most favourable trade-off between ischemic and bleeding events, among CAD patients eligible to COMPASS. Methods We identified the “COMPASS eligible population” (CEP) within the CLARIFY Registry (n = 15.185). Patients at high bleeding risk (REACH BRS > 10) were excluded in accordance with COMPASS protocol. Patients were categorized as low-intermediate (0–1) or high (≥ 2) CHA2DS2VaSc; low (0–12) or intermediate (13–19) REACH RIS, and low (0–6) or intermediate (7–10) REACH BRS. Ischemic outcome: CV death, MI or stroke. Bleeding outcome: bleeding leading to admission, transfusion, or haemorrhagic stroke (100 patients-year). Results The CEP comprised 5.142 patients (33.9%). Ischemic and bleeding outcome for CEP were 2.3 [2.1–2.5] and 0.5 [0.4–0.6]/100 patient-years, respectively. Patients with high CHA2DS2VaSc score, intermediate REACH BRS and RIS represented 95.5%, 83.8%, and 37.6% (n = 1.934) of the population. Regarding ischemic risk, patients with intermediate REACH RIS had the higher ischemic risk (3.0 [2.6–3.4] vs. 1.9 [1.7–2.1], P Fig. 1 ). Conclusions Low CHA2DS2VaSc scores identify a small subset of patients with very low ischemic risk, which is unlikely to benefit from the adjunction of low dose rivaroxaban to standard therapy. Patients with intermediate REACH RIS had higher ischemic risk, without increased bleeding risk.

Background A previous analysis of the REACH Registry showed that 52.9% of stable vascular patients were eligible to COMPASS. However, data regarding eligibility to COMPASS in CAD patients from real life practice are scarce. Purpose To describe the proportion, management and outcomes of patients eligible to COMPASS and to compare patients excluded, eligible, and who did not meet the “enrichment criteria” (COMPASS Excluded, Eligible and Not Included). Methods We used the CLARIFY Registry (> 30.000 stable CAD patients). According to COMPASS protocol, patients with a REACH bleeding risk score (BRS) > 10, heart failure, severe renal failure, need for dual antiplatelet therapy (DAPT), or anticoagulant therapy were excluded. Then, COMPASS inclusion criteria were applied: CAD patients had to be > 65 years, if younger, have documented atherosclerosis, or at least two enrichment criteria (current smoker, diabetes, GFR Results A total of 15.185 patients had comprehensive data allowing precise assessment of eligibility, from which 43.1% had at least one exclusion criteria, 23.1% did not have enrichment criteria and 33.9% were eligible. The vast majority were excluded due to high bleeding risk (62.7% needing DAPT, and 52.7% for high REACH BRS). Ischemic and bleeding outcome (100 patients/year) were 2.3 [2.1–2.5] and 0.5 [0.4–0.6] respectively for COMPASS-Eligible, 3.0 [2.8–3.2] and 0.6 [0.5–0.7] for COMPASS-Excluded and 1.2 [1.0–1.4] and 0.2 [0.2–0.3] for COMPASS-Not Included. Conclusion In a large registry of stable CAD patients, approximately one of three patients was potentially eligible for adjunction of low-dose rivaroxaban to aspirin, and remains at high risk of ischemic outcome. COMPASS-Excluded had the worse ischemic and bleeding outcomes and represent a group in need of improved therapy.