Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry.

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 < 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4-7.3)] or without angina [6.4% (95% CI 5.9-7.0)], 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.

Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals.

BACKGROUND: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. METHODS AND RESULTS: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). CONCLUSIONS: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.

Blended Learning Compared to Traditional Learning in Medical Education: Systematic Review and Meta-Analysis.

BACKGROUND: Blended learning, which combines face-to-face learning and e-learning, has grown rapidly to be commonly used in education. Nevertheless, the effectiveness of this learning approach has not been completely quantitatively synthesized and evaluated using knowledge outcomes in health education. OBJECTIVE: The aim of this study was to assess the effectiveness of blended learning compared to that of traditional learning in health education. METHODS: We performed a systematic review of blended learning in health education in MEDLINE from January 1990 to July 2019. We independently selected studies, extracted data, assessed risk of bias, and compared overall blended learning versus traditional learning, offline blended learning versus traditional learning, online blended learning versus traditional learning, digital blended learning versus traditional learning, computer-aided instruction blended learning versus traditional learning, and virtual patient blended learning versus traditional learning. All pooled analyses were based on random-effect models, and the I2 statistic was used to quantify heterogeneity across studies. RESULTS: A total of 56 studies (N=9943 participants) assessing several types of learning support in blended learning met our inclusion criteria; 3 studies investigated offline support, 7 studies investigated digital support, 34 studies investigated online support, 8 studies investigated computer-assisted instruction support, and 5 studies used virtual patient support for blended learning. The pooled analysis comparing all blended learning to traditional learning showed significantly better knowledge outcomes for blended learning (standardized mean difference 1.07, 95% CI 0.85 to 1.28, I2=94.3%). Similar results were observed for online (standardized mean difference 0.73, 95% CI 0.60 to 0.86, I2=94.9%), computer-assisted instruction (standardized mean difference 1.13, 95% CI 0.47 to 1.79, I2=78.0%), and virtual patient (standardized mean difference 0.62, 95% CI 0.18 to 1.06, I2=78.4%) learning support, but results for offline learning support (standardized mean difference 0.08, 95% CI -0.63 to 0.79, I2=87.9%) and digital learning support (standardized mean difference 0.04, 95% CI -0.45 to 0.52, I2=93.4%) were not significant. CONCLUSIONS: From this review, blended learning demonstrated consistently better effects on knowledge outcomes when compared with traditional learning in health education. Further studies are needed to confirm these results and to explore the utility of different design variants of blended learning.

ß-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study.

AIMS: The effect of first-line antianginal agents, ß-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. METHODS AND RESULTS: We analysed the use of ß-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 ß-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 ß-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline ß-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, ß-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.

Potential impact of the 2017 ACC/AHA guideline on high blood pressure in normotensive patients with stable coronary artery disease: insights from the CLARIFY registry.

Aims: 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. Methods and results: Data from 5956 patients with stable coronary artery disease, no history of hypertension or heart failure, and average BP <140/90 mmHg, enrolled in the CLARIFY registry (November 2009 to June 2010), were analysed. In a multivariable-adjusted Cox proportional hazards model, after a median follow-up of 5.0 years, diastolic BP 80-89 mmHg, but not systolic BP 130-139 mmHg, was associated with increased risk of the primary endpoint, a composite of cardiovascular death, myocardial infarction, or stroke (hazard ratio 2.15, 95% confidence interval 1.22-3.81 vs. 70-79 mmHg and 1.12, 0.64-1.97 vs. 120-129 mmHg). No significant increase in risk for the primary endpoint was observed for systolic BP <120 mmHg or diastolic BP <70 mmHg. Conclusion: In patients with stable coronary artery disease defined as having normal BP according to the 140/90 mmHg threshold, diastolic BP 80-89 mmHg was associated with increased cardiovascular risk, whereas systolic BP 130-139 mmHg was not, supporting the lower diastolic but not the lower systolic BP hypertension-defining threshold and treatment target in coronary artery disease. ClinicalTrials identifier: ISRCTN43070564.

External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registry.

Aims: The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial. Methods and results: The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001). Conclusion: COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm.

Prognostic and diagnostic value of elevated serum concentration of procalcitonin in patients with suspected heart failure. A review and meta-analysis.

PURPOSE: The diagnostic and prognostic significance of procalcitonin remains uncertain in HF patients. We reviewed and performed a meta-analysis of studies that measured PCT in HF patients, with or without infection. MATERIALS AND METHODS: We identified seven studies (9514 patients, 5810 with diagnoses of HF) eligible for our analysis, out of 247 examined. We estimated the serum PCT concentrations in patients with and without HF and/or infection and examined the mortality rates of patients with versus without elevated serum PCT concentrations. RESULTS: The mean age of the study samples ranged between 58 and 81 years, the men proportion between 47% and 66%, the follow-up duration between 22 and 180 days. The median PCT concentration in patients with HF and concomitant infections tended to be higher (0.26 ng/l [0.06, 0.46]) than in patients with HF alone (0.10 ng/l [0.08, 0.12]; p = 0.059). The mortality of patients suffering from HF and whose serum PCT concentrations were elevated was significantly higher than that of patients suffering from HF whose PCT concentrations were normal at 30 (2.66 [1.74, 4.05]), 90 (2.12 [1.59, 2.83]) and 180 days (2.06 [1.13, 3.78]). CONCLUSIONS: In patients with HF, an elevated serum PCT concentration predicted the short-term risk of death.

Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes.

Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. METHODS: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. RESULTS: A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P>0.05) CONCLUSIONS: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure.

AIMS: The aim of this study was to determine whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) use is associated with lower rates of cardiovascular events in patients with stable coronary artery disease (CAD) but without heart failure (HF) receiving contemporary medical management. METHODS AND RESULTS: Using data from the Reduction of Atherothrombosis for Continued Health (REACH) registry, we examined, using propensity score approaches, relationships between cardiovascular outcomes and ACEI/ARB use (64.1% users) in 20 909 outpatients with stable CAD and free of HF at baseline. As internal control, we assessed the relation between statin use and outcomes. At 4-year follow-up, the risk of cardiovascular death, MI, or stroke (primary outcome) was similar in ACEI/ARB users compared with non-users (hazard ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.66). Similarly, the risk of the primary outcome and cardiovascular hospitalization for atherothrombotic events (secondary outcome) was not reduced in ACEI/ARB users (hazard ratio, 1.08; 95% CI, 1.01-1.16; P = 0.04), nor were the rates of any of its components. Analyses using propensity score matching yielded similar results, as did sensitivity analyses accounting for missing covariates, changes in medications over time, or analysing separately ACEI and ARB use. In contrast, in the same cohort, statin use was associated with lower rates for all outcomes. CONCLUSIONS: Use of ACEI/ARB was not associated with better outcomes in stable CAD outpatients without HF. The benefit of ACEI/ARB seen in randomized clinical trials was not replicated in this large contemporary cohort, which questions their value in this specific subset.

Impact of diabetes mellitus and metabolic syndrome on acute and chronic on-clopidogrel platelet reactivity in patients with stable coronary artery disease undergoing drug-eluting stent placement.

BACKGROUND: Previous studies, which compared the prevalence of high on-clopidogrel platelet reactivity (HCPR) in type 2 diabetes mellitus (T2DM) versus non-T2DM and obese versus nonobese patients provided conflicting results. METHODS: We compared the prevalence of HCPR in patients with T2DM, metabolic syndrome (MS), or neither T2DM nor MS undergoing drug-eluting stent implantation for stable coronary artery disease. Platelet functions were measured after a 600-mg clopidogrel loading dose and after 4 months on clopidogrel 75 mg/d. RESULTS: The prevalence of HCPR was significantly higher in 63 T2DM and 50 MS patients than in 43 patients with neither T2DM nor MS (46.0% and 52.0% vs 20.9%) after clopidogrel loading dose, whereas, at 4 months, only T2DM patients had a significantly higher prevalence of HCPR (50.8% and 31.3% vs 23.8%). By multivariable analysis, T2DM (odds ratio [OR] 3.62, 95% CI, 1.34-9.80, P = .011), MS (OR 4.00, 95% CI 1.39-11.46, P = .010), and previous chronic treatment with clopidogrel (OR 0.22, 95% CI 0.09-0.49; P < .001) were the main independent predictors of HCPR after clopidogrel loading dose, whereas only T2DM (OR 2.98, 95% CI 1.20-7.41, P = .017) was an important independent predictor of HCPR at 4 months. CONCLUSIONS: Both MS and T2DM were independent predictors of HCPR after clopidogrel loading dose. On clopidogrel maintenance therapy, only T2DM remained an independent predictor. This observation may be clinically relevant in the current era of antiplatelet therapy.

In vitro and in vivo evidence for the role of elastase shedding of CD163 in human atherothrombosis.

AIMS: CD163 is a macrophage receptor for haemoglobin-haptoglobin (Hb-Hp) complexes, responsible for the clearance of haemoglobin. We hypothesized that production of soluble CD163 (sCD163) may be due to proleolytic shedding of membrane CD163 by neutrophil elastase, reported to be increased in culprit atherosclerotic plaques. We analysed the relationship between CD163 solubilization and elastase in vitro, in macrophage culture, ex vivo in human atherosclerotic plaque samples, and in vivo, in plasma of patients with coronary artery disease. METHODS AND RESULTS: Neutrophil elastase was shown to enhance CD163 shedding and to decrease the uptake of Hb-Hp complexes by cultured macrophages. In addition, cultured carotid endarterectomy samples showing features of intraplaque haemorrhage released more sCD163 and elastase/α1-antitrypsin (α1-AT) complexes than non-haemorrhagic plaques (n= 44). Plasma levels of sCD163 and neutrophil elastase (complexed with α1-AT) were measured in patients with an acute coronary syndrome (ACS, n= 42), stable angina pectoris (SAP, n= 28), or normal coronary angiograms without subclinical atherosclerosis (n= 21). Acute coronary syndrome patients had higher sCD163 and elastase/α1-AT complexes plasma concentrations than subjects without coronary atherosclerosis. Circulating sCD163 and elastase/α1-AT complexes were positively correlated in patients with ACS (r = 0.56, P< 0.0002) and SAP (r = 0.62, P< 0.0005). CONCLUSION: Our results suggest that neutrophil elastase promotes CD163 shedding, resulting in a decreased clearance of Hb by macrophages, which may favour plaque destabilization. This may be reflected by increased plasma levels of sCD163 and elastase/α1-AT complexes which are positively correlated in patients with coronary artery disease.

Prevalence of diabetes and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities.

BACKGROUND: In 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 RESULTS: CLARIFY 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. CONCLUSION: In 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 IDENTIFIER: ISRCTN43070564.

The lead story of the fire at the Notre-Dame cathedral of Paris.

On 15th April 2019, Parisians watched in shock as Notre-Dame de Paris, the iconic cathedral that has towered over their city for almost 900 years, was engulfed in flames. Although flames destroyed the spire and considerably weakened the structure, no human lives were lost. However, as some amounts of lead volatilized and deposited in the surrounding areas, fears of potential intoxication began to rise. We investigated the impact of this fire on the blood lead levels of adults in Paris according to the distance between the cathedral and where they live or work. The geometric mean of blood lead levels of the study population was 1.49µg/dl (95% CI [1.38-1.62]) with a prevalence of blood lead levels≥5.0µg/dL of 5.0%. Despite the early legitimate fears of intoxication, the fire that destroyed a significant part of the Notre-Dame cathedral did not increase the blood lead levels of adults living and working in the vicinity.

Simple risk models to predict cardiovascular death in patients with stable coronary artery disease.

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).

Prevalence, Incidence and Prognostic Implications of Left Bundle Branch Block in Patients with Chronic Coronary Syndromes (From the CLARIFY Registry).

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], p < 0.001) and permanent pacemaker implantation (HR 2.11, 95% CI [1.45 - 3.07], p < 0.001). 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.

Use of risk scores to identify lower and higher risk subsets among COMPASS-eligible patients with chronic coronary syndromes. Insights from the CLARIFY registry.

BACKGROUND: 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. HYPOTHESIS: The CHA2 DS2 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. METHODS: 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) CHA2 DS2 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). RESULTS: 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 CHA2 DS2 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]). CONCLUSIONS: Intermediate REACH RIS identified potential optimal candidates for adjunction of low-dose rivaroxaban while patients with low CHA2 DS2 VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding.

Prevalence, clinical determinants and prognostic implications of coronary procedural complications of percutaneous coronary intervention in non-ST-segment elevation myocardial infarction: Insights from the contemporary multinational TAO trial.

BACKGROUND: Few data are available on procedural complications of percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome in the contemporary era. AIM: We sought to describe the prevalence of procedural complications of PCI in a non-ST-segment elevation acute coronary syndrome (NSTE ACS) cohort, and to identify their clinical characteristics and association with clinical outcomes. METHODS: Patients randomized in TAO (Treatment of Acute coronary syndrome with Otamixaban), an international randomized controlled trial (ClinicalTrials.gov Identifier: NCT01076764) that compared otamixaban with unfractionated heparin plus eptifibatide in patients with NSTE ACS who underwent PCI, were included in the analysis. Procedural complications were collected prospectively, categorized and adjudicated by a blinded Clinical Events Committee, with review of angiograms. A multivariable model was constructed to identify independent clinical characteristics associated with procedural complications. RESULTS: A total of 8656 patients with NSTE ACS who were enrolled in the TAO trial underwent PCI, and 451 (5.2%) experienced at least one complication. The most frequent complications were no/slow reflow (1.5%) and dissection with decreased flow (1.2%). Procedural complications were associated with the 7-day ischaemic outcome of death, myocardial infarction or stroke (24.2% vs. 6.0%, odds ratio 5.01, 95% confidence interval 3.96-6.33; P<0.0001) and with Thrombolysis In Myocardial Infarction major and minor bleeding (6.2% vs. 2.3%, odds ratio 2.79, 95% confidence interval 1.86-4.2; P<0.0001). Except for previous coronary artery bypass grafting, multivariable analysis did not identify preprocedural clinical predictors of complications. CONCLUSIONS: In a contemporary NSTE ACS population, procedural complications with PCI remain frequent, are difficult to predict based on clinical characteristics, and are associated with worse ischaemic and haemorrhagic outcomes.

Direct-acting Anticoagulants in Chronic Coronary Syndromes.

Direct-acting oral anticoagulants (DOACs) are easier to use, safer than and as effective as vitamin K antagonists (VKA) in the treatment of non-valvular AF (NVAF). Because of their favourable safety profile and easier use than VKAs, DOACs as anti-thrombotic therapy may have a role in the management of chronic coronary syndromes (CCS). To date, few studies have evaluated DOACs in this setting. Initial studies have focused on patients receiving DOACs for NVAF undergoing acute or elective percutaneous coronary intervention who additionally require dual antiplatelet therapy (DAPT). Rivaroxaban 15 mg once daily plus a P2Y12 inhibitor compared with a VKA regimen was associated with a reduction of bleedings (HR 0.59; 95% CI [0.47-0.76]; p<0.001). Rivaroxaban 2.5 mg twice daily plus DAPT up to 12 months followed by rivaroxaban 15 mg once daily plus P2Y12 inhibitor showed similar results. Dabigatran 110 mg twice daily plus a P2Y12 inhibitor versus a VKA regimen was associated with a reduction of bleedings (HR 0.52; 95% CI [0.42-0.63]; p<0.001), after a mean follow-up of 14 months. A dabigatran 150 mg regimen showed similar results. Apixaban 5 mg twice daily plus a P2Y12 inhibitor versus a VKA regimen confirmed at 6 months the safety of DOACs with a reduction of bleedings (HR 0.69; 95% CI [0.58-0.81]; p<0.001 for non-inferiority and superiority). Edoxaban 60 mg once daily plus a P2Y12 inhibitor was non-inferior to a VKA regimen on bleeding outcomes (major bleeding or non-major clinically relevant non-major bleeding) after a 12-month follow-up (HR 0.83; 95% CI [0.65-1.05]; p=0.001 for non-inferiority; p=0.1154 for superiority). Meta-analysis of these four trials confirmed the safety of DOACs regarding bleeding outcomes, but showed a trend toward stent thrombosis for dual antithrombotic therapy using DOACs versus triple antithrombotic therapy using VKAs. DOACs may show promise in the management of high-risk patients with chronic coronary syndromes. In these patients, rivaroxaban 2.5 mg twice daily in addition to aspirin was shown to reduce the composite outcome of cardiovascular death, stroke or MI compared to aspirin alone (HR 0.76; 95% CI [0.66-0.86]; p<0.001). All-cause death, cardiovascular death and stroke were also significantly lower. This benefit was at the cost of an increase in non-fatal bleeding.

Patterns of hypertension management in France in 2015: The ESTEBAN survey.

The purposes of this study were to describe the hypertensive population and therapeutic management of hypertension in adults between 18 and 74 years of age in France in 2015. Esteban survey is a cross-sectional survey with a clinical examination conducted in a representative sample of French adults aged 18-74 years between 2014 and 2016. Esteban was entirely public-funded. Blood pressure (BP) was measured during clinical examination with a standardized protocol, and pharmacological treatment was collected through the exhaustive Système National des Données de Santé (SNDS) database. Hypertension was defined by systolic BP (SBP)> 140 mm Hg, diastolic BP (DBP)> 90 mm Hg or treatment with BP-lowering drugs. The therapeutic control of treated hypertensive patients was defined by SBP < 140 mm Hg and DBP < 90 mm Hg. Adherence to drug treatment was defined as more than 80% of days covered by BP-lowering drug per year. The prevalence of hypertension was 31.3%. 74.7% of aware hypertensive participants taking an antihypertensive drug, and 57.7% of them were treated with a single antihypertensive pharmacological class. Overall, among hypertensives, 24.3% had a satisfactory BP control. Only 49.7% of treated hypertensives participants were controlled, and 33.6% of them were adherent to their drug treatment. The prevalence of hypertension in France remains high, with only 74.7% of the aware hypertensive participants receiving pharmacological therapy and only 48.9% of aware hypertensives with a BP at goal. More effective measures are needed to improve clinical management of hypertension in France.

Relationship between physical activity and long-term outcomes in patients with stable coronary artery disease.

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.