Relative Importance of Heart Failure Events Compared to Stroke and Bleeding in AF Patients.

INTRODUCTION: Incident heart failure (HF), ischemic stroke and systemic embolism (IS/SE), and major bleeding related to anticoagulation therapy are still the most frequent events occurring in patients with atrial fibrillation (AF). The aim of this study was to assess the 3-year incidence, predictors, and related mortality of IS/SE, major bleeding, and HF in a large cohort of AF outpatients. METHODS AND RESULTS: We studied 4973 outpatients with prevalent AF included in the CARDIONOR registry. The mean age was 72.9 ± 11.2 years, 24.1% had diabetes mellitus and 78.9% had anticoagulant therapy at baseline. The mean CHA2DS2Vasc score was 3.4 ± 1.7. After a median follow-up of 3.2 years (IQR: 2.8 to 3.5), incident HF, IS/SE and major bleeding occurred in 10.5%, 3.3% and 2.1% of patients, respectively. When analyzed as time-dependent variables, IS/SE, major bleeding and hospitalization for decompensated HF were all strongly associated with mortality. The independent predictors of incident HF were age, women, hypertension, diabetes mellitus, coronary artery disease and a previous history of HF. A sensitivity analysis in patients without history of HF at inclusion revealed that incident HF remained the most frequent adverse event, occurring in 5.3% of patients, compared to IS/SE (1.7%) and major bleeding (2.5%). CONCLUSION: HF is a common residual cardiovascular adverse event occurring in AF outpatients and is associated with a very high mortality. Since modifiable risk factors are associated with incident HF, upstream intensive management of these risk factors would be of interest.

Real-Life Incident Atrial Fibrillation in Outpatients with Coronary Artery Disease.

Background: The risk, correlates, and consequences of incident atrial fibrillation (AF) in patients with chronic coronary artery disease (CAD) are largely unknown. Methods and results: We analyzed incident AF during a 3-year follow-up in 5031 CAD outpatients included in the prospective multicenter CARDIONOR registry and with no history of AF at baseline. Incident AF occurred in 266 patients (3-year cumulative incidence: 4.7% (95% confidence interval (CI): 4.1 to 5.3)). Incident AF was diagnosed during cardiology outpatient visits in 177 (66.5%) patients, 87 of whom were asymptomatic. Of note, 46 (17.3%) patients were diagnosed at time of hospitalization for heart failure, and a few patients (n = 5) at the time of ischemic stroke. Five variables were independently associated with incident AF: older age (p < 0.0001), heart failure (p = 0.003), lower left ventricle ejection fraction (p = 0.008), history of hypertension (p = 0.010), and diabetes mellitus (p = 0.033). Anticoagulant therapy was used in 245 (92%) patients and was associated with an antiplatelet drug in half (n = 122). Incident AF was a powerful predictor of all-cause (adjusted hazard ratio: 2.04; 95% CI: 1.47 to 2.83; p < 0.0001) and cardiovascular mortality (adjusted hazard ratio: 2.88; 95% CI: 1.88 to 4.43; p < 0.0001). Conclusions: In CAD outpatients, real-life incident AF occurs at a stable rate of 1.6% annually and is frequently diagnosed in asymptomatic patients during cardiology outpatient visits. Anticoagulation is used in most cases, often combined with antiplatelet therapy. Incident AF is associated with increased mortality.

Secondary prevention and outcomes in outpatients with coronary artery disease, atrial fibrillation or heart failure: a focus on disease overlap.

Objective: To assess secondary prevention and outcomes in patients with chronic coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF), focusing on disease overlap. Methods: We analysed the data of 10 517 outpatients with a diagnosis of CAD, AF and/or HF included in a prospective cohort study. Follow-up (median 3.2 years) was achieved in 10 478 (99.6%) patients. Seven mutually exclusive patient groups were formed: CAD alone (n=4303), AF alone (n=2604), CAD+AF (n=700), HF alone (n=513), HF+CAD (n=728), HF+AF (n=1087) and HF+CAD+AF (n=582). Results: Patients with disease overlaps represented 29.4% of the total population. The level of secondary prevention was high in all subgroups and in accordance with European class I - level A guidelines. Among patients with CAD, 99% received an antithrombotic and 91% received a statin. Among patients with AF, 81.7% were treated with an anticoagulant if indicated. Among HF patients with left ventricular ejection fraction <40%, 90.9% received a renin-angiotensin system antagonist and 91% a beta-blocker. Three-year all cause/cardiovascular mortality rates were: 6.4%/2%, 9.7%/3.3%, 15.6%/6.7%, 19.2%/9.4%, 24.3%/13.6%, 28%/15.7% and 35.4%/24.8%, for patients with CAD alone, AF alone, CAD+AF, HF alone, HF+CAD, HF+AF and HF+CAD+AF, respectively. In all groups with HF, observed all-cause mortality was higher (p<0.0001) than expected mortality for age-matched, gender-matched and geography-matched persons. In contrast, observed mortality was lower than expected for patients with CAD alone and AF alone (p<0.0001). Conclusions: In a context of adequate secondary prevention, overlap between diseases is a frequent and high-risk situation with incremental increases in mortality. These patients deserve specific attention.

Gender differences in clinical characteristics, medical management, risk factor control, and long-term outcome of patients with stable coronary artery disease: from the CORONOR registry.

BACKGROUND: Conflicting information exists about whether sex differences modulate outcome in patients with coronary artery disease (CAD). Our aim was to analyze baseline characteristics, medical management, risk factor control, and long-term outcome according to gender in patients with stable CAD. METHODS: We analyzed data from the contemporary multicenter CORONOR registry, which included 4184 consecutive outpatients with stable CAD. Follow-up was performed at 5 years with adjudication of clinical events. RESULTS: There were 3252 (77.7%) men and 932 (22.3%) women. Women were older than men, more likely to have hypertension, and less likely to smoke. They had more frequent angina but less frequent multivessel CAD. Evidence-based medications were widely used with only few differences according to gender. Women had a poorer control of cardiovascular risk with higher systolic blood pressure and LDL-cholesterol. The composite endpoint - cardiovascular death, myocardial infarction, or ischemic stroke - occurred in 536 patients. When adjusted for baseline characteristics, five-year outcomes were similar for women and men for the composite endpoint (Hazard ratio [95% confidence interval]: 1.03 [0.81-1.31], P=0.817). CONCLUSIONS: In contemporary practice, women with stable CAD had a poorer control of cardiovascular risk. However, at 5-year follow-up, cardiovascular outcomes were similar for both genders.

First Hospitalization for Heart Failure in Outpatients With Stable Coronary Artery Disease: Determinants, Role of Incident Myocardial Infarction, and Prognosis.

BACKGROUND: We lack recent data on the incidence, correlates, and prognosis associated with heart failure (HF) development in patients with stable coronary artery disease (CAD). Here, we analyzed HF development in a contemporary population of outpatients with stable CAD. METHODS AND RESULTS: Of 4184 unselected outpatients with stable CAD (ie, myocardial infarction [MI] and/or coronary revascularization >1 year earlier) included in the multicenter CORONOR registry, we identified 3871 patients with no history of hospitalization for HF at inclusion and followed 3785 (98%) of them for 5 years. During follow-up, 211 patients were hospitalized for HF (5-year cumulative incidence 5.7%) and 163 patients had incident MIs. Independent predictors of hospitalization for HF were older age, lower left ventricular ejection fraction (LVEF), atrial fibrillation, higher body mass index, diabetes mellitus, history of hypertension, angina at inclusion, and multivessel CAD. Most hospitalizations for HF (62.6%) occurred in patients with LVEF ≥50% at inclusion, and most (92.4%) were not preceded by an incident MI. Hospitalization for HF was a powerful predictor of mortality (adjusted hazard ratio 5.97, 95% confidence interval 4.55-7.83; P < .0001). After hospitalization for HF, mortality rates were similar in patients with LVEFs ≥50% and <50% at hospitalization. CONCLUSIONS: Outpatients with stable CAD were frequently hospitalized for HF, and HF was associated with high mortality. Most HF hospitalizations were associated with preserved LVEF at inclusion and were not preceded by an incident MI.

Elective Coronary Revascularization Procedures in Patients With Stable Coronary Artery Disease: Incidence, Determinants, and Outcome (From the CORONOR Study).

OBJECTIVES: The authors sought to describe the incidence, determinants, and outcome of elective coronary revascularization (ECR) in patients with stable coronary artery disease (CAD). BACKGROUND: Observational data are lacking regarding the practice of ECR in patients with stable CAD receiving modern secondary prevention. METHODS: The authors analyzed coronary revascularization procedures performed during a 5-year follow-up in 4,094 stable CAD outpatients included in the prospective multicenter CORONOR (Suivi d'une cohorte de patients COROnariens stables en région NORd-Pas-de-Calais) registry. RESULTS: Secondary prevention medications were widely prescribed at inclusion (antiplatelet agents 96.4%, statins 92.2%, renin-angiotensin system antagonists 81.8%). A total of 481 patients underwent ≥1 coronary revascularization procedure (5-year cumulative incidences of 3.6% [0.7% per year] for acute revascularizations and 8.9% [1.8% per year] for ECR); there were 677 deaths during the same period. Seven baseline variables were independently associated with ECR: prior coronary stent implantation (p < 0.0001), absence of prior myocardial infarction (p < 0.0001), higher low-density lipoprotein cholesterol (p < 0.0001), lower age (p < 0.0001), multivessel CAD (p = 0.003), diabetes mellitus (p = 0.005), and absence of treatment with renin-angiotensin system antagonists (p = 0.020). Main indications for ECR were angina associated with a positive stress test (31%), silent ischemia (31%), and angina alone (25%). The use of ECR had no impact on the subsequent risk of death, myocardial infarction, or ischemic stroke (hazard ratio: 1.04; 95% confidence interval: 0.76 to 1.41). CONCLUSIONS: These real-life data show that ECR is performed at a rate of 1.8% per year in stable CAD patients widely treated by secondary medical prevention. ECR procedures performed in patients without noninvasive stress tests are not rare. Having an ECR was not associated with the risk of ischemic adverse events.

Association of Diabetic Status and Glycemic Control With Ischemic and Bleeding Outcomes in Patients With Stable Coronary Artery Disease: The 5-Year CORONOR Registry.

BACKGROUND: The relation between diabetes mellitus, glycemic control, and ischemic and bleeding events is poorly described in outpatients with stable coronary artery disease receiving modern secondary prevention. METHODS AND RESULTS: The multicenter CORONOR (Suivi d'une cohorte de patients Coronariens stables en région Nord-pas-de-Calais) registry enrolled 4184 outpatients with stable coronary artery disease, including 1297 patients (31%) with diabetes mellitus. A recent glycosylated hemoglobin (HbA1c) was available for 1146 diabetic patients, and 48% had HbA1c ≥7%. We analyzed 5-year ischemic (cardiovascular death, myocardial infarction, and stroke) and bleeding (Bleeding Academic Research Consortium ≥3) outcomes, according to diabetic status and glycemic control. When compared with nondiabetic patients, the ischemic risk was higher in diabetic patients with HbA1c ≥7% (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.25-1.93) but not in diabetic patients with HbA1c <7% (HR, 1.06; 95% CI, 0.83-1.36). Diabetic patients with HbA1c ≥7% were at higher risk than diabetic patients with HbA1c <7% (HR, 1.47; 95% CI, 1.09-1.98). When compared with nondiabetic patients, the bleeding risk was higher in diabetic patients, with HbA1c <7% (HR, 1.66; 95% CI, 1.04-2.67) and in those with HbA1c ≥7% (HR, 1.75; 95% CI, 1.07-2.86). No difference in bleeding risk was observed between diabetic patients with HbA1c ≥7% versus those with HbA1c <7%. Similar results were obtained when adjusted for baseline characteristics. CONCLUSIONS: The 5-year increased risk of ischemic events in patients with stable coronary artery disease with diabetes mellitus was restricted to those with HbA1c ≥7%. By contrast, the increase in bleeding risk associated with diabetes mellitus was observed in patients with HbA1c ≥7% and in patients with HbA1c <7%. The level of HbA1c should be taken into account for future research and may help physicians to manage prolonged antithrombotic therapies in this high-risk subgroup.

Reaching low-density lipoprotein cholesterol treatment targets in stable coronary artery disease: Determinants and prognostic impact.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) reduction is an integral part of the management of patients with coronary artery disease (CAD). AIMS: To assess attainment of LDL-C goals during long-term treatment of patients with stable CAD, and to determine predictors of goal attainment and the prognostic impact of reaching LDL-C<70mg/dL (1.8mmol/L) in a real-life setting. METHODS: Data were obtained for 4080 outpatients with stable CAD included in the multicentre CORONOR study. Five-year follow-up was achieved for 3991 (97.8%) patients. RESULTS: At inclusion, a recent (<1 year) measurement of LDL-C was available in 3757 (92.1%) patients. LDL-C<70mg/dL was reached by 885 (23.6%) patients. Independent predictors of LDL-C<70mg/dL were diabetes mellitus, statin treatment, treatment with renin-angiotensin system inhibitors, previous myocardial infarction and short time since last coronary event. The adjusted hazard ratio (HR) for the composite endpoint (cardiovascular death, myocardial infarction, ischemic stroke or coronary revascularization) during the 5-year follow-up was 1.31 (95% confidence interval [CI]: 1.09-1.58; P=0.004) for LDL-C≥70mg/dL versus<70mg/dL. When compared with patients with LDL-C<70mg/dL, the adjusted HRs for LDL-C 70-99mg/dL and ≥100mg/dL (2.6mmol/L) were 1.27 (95% CI: 1.05-1.55; P=0.016) and 1.38 (95% CI: 1.12-1.70; P=0.003), respectively. When LDL-C was used as a continuous variable, the adjusted HRs for increases of 10mg/dL (0.3mmol/L) and 1mmol/L were 1.05 (95% CI: 1.03-1.08) and 1.21 (95% CI: 1.10-1.33), respectively. CONCLUSIONS: In this observational study, only a minority of stable CAD patients had LDL-C<70mg/dL. The patients who reached their LDL-C goal had the lowest risk of cardiovascular events.

Long-term risk and predictors of cardiovascular death in stable coronary artery disease: the CORONOR study.

BACKGROUND: There is limited knowledge on the residual risk of cardiovascular death (CVD) in patients with stable coronary artery disease (CAD) who receive modern secondary prevention. Our aim was to analyze the causes of death and to determine predictors of CVD in the 5-year CORONOR registry. METHODS: We studied 4184 consecutive CAD outpatients who were free from any myocardial infarction (MI) or coronary revascularization for more than 1 year at inclusion. Antithrombotics were prescribed in 99%, statins in 92%, inhibitors of renin-angiotensin system in 82%, and ß-blockers in 79%; 86% had prior coronary revascularization. Follow-up was performed at 5 years with adjudication of the causes of death. RESULTS: There were 677 deaths during follow-up. The cause of death was cardiovascular in 269 patients (1.3%/year), with 99 deaths from heart failure (HF), 91 sudden deaths, and 65 vascular deaths (stroke, MI, limb or mesenteric ischemia, aortic aneurysm). Predictors of CVD were age [subhazard ratio (SHR)=1.06 (1.04-1.07) per year increase], previous hospitalization for decompensated HF [SHR=3.10 (2.19-4.40)], left ventricular ejection fraction [SHR=0.97 (0.96-0.98) per percentage increase], prior aortic or peripheral intervention [SHR=1.61 (1.12-2.13)], and estimated glomerular filtration rate [SHR=0.99 (0.98-1.00)] per ml/min/1.73m increase]. In analyses stratified on age, prior HF, and left ventricular ejection fraction, the estimated 5-year cardiovascular mortality rates varied from less than 2% to more than 50%. CONCLUSION: In stable CAD patients widely treated by secondary prevention medications, the main causes of CVD are death from HF and sudden death. The risk of CVD can be predicted by simple baseline variables. New therapeutic strategies are needed for the high-risk patients.

Incident Myocardial Infarction and Very Late Stent Thrombosis in Outpatients With Stable Coronary Artery Disease.

BACKGROUND: Current data are lacking for incidence, correlates, and prognosis associated with incident myocardial infarction (MI) in patients with stable coronary artery disease (CAD). Furthermore, the contribution of very late stent thrombosis (VLST) to these events remains poorly understood. OBJECTIVES: This study aimed to analyze the residual risk of MI, together with relevant associated factors, and related mortality in stable CAD outpatients. METHODS: The multicenter CORONOR (Suivi d'une cohorte de patients COROnariens stables en region NORd-Pas-de-Calais) study enrolled 4,184 unselected outpatients with stable CAD (i.e., MI or coronary revascularization >1 year previously). Five-year follow-up was achieved for 4,094 patients (98%). RESULTS: We identified a linear risk of incident MI (0.8% annually), with ST-segment elevation MI constituting one-third of all cases. Current smoking, low-density lipoprotein cholesterol, multivessel CAD, diabetes with glycosylated hemoglobin >7%, and persistent angina were all associated with increased risk, and prior bypass surgery was associated with decreased risk. When used as a time-dependent variable, incident MI was associated with an increased risk of death (hazard ratio: 2.05; p < 0.0001). Among patients with prior stent implantation, VLST was causal in 20% of MI cases and presented more often as ST-segment elevation MI versus MI not related to a stented site (59% vs. 26%, p = 0.001). Adjusted mortality was 4 times higher in patients with VLST than in MI not related to a stented site. CONCLUSIONS: In stable CAD outpatients, incident MI occurs at a stable rate of 0.8% annually, is related to VLST in one-fifth of cases, and is associated with an increased mortality risk, especially for VLST. Multivessel CAD and residual uncontrolled risk factors are strongly associated with MI.

Effect of left ventricular systolic dysfunction on secondary medical prevention and clinical outcome in stable coronary artery disease patients.

BACKGROUND: Limited recent data are available in the literature on whether the presence of left ventricular systolic dysfunction (LVSD) affects the therapeutic management of patients with stable coronary artery disease (CAD). AIMS: The objectives of this study were to analyse prevalence, effect on therapeutics and prognosis of LVSD in stable CAD. METHODS: We prospectively included 4184 CAD outpatients free from any myocardial infarction or coronary revascularization for>1year. Left ventricular ejection fraction (EF) was available for 4124 (98.6%) patients. Follow-up was performed at 2years. All events were adjudicated blindly. RESULTS: The mean EF was 57.5±10.8%, and 201 (4.9%) patients had an EF≤35%. The prescription of renin-angiotensin system inhibitors and beta-blockers was inversely related to EF, and reached>90% in patients with EF≤35%. Seventy-five (37.3%) of the patients with EF≤35% received a mineralocorticoid receptor antagonist. Eighty-five (42.3%) of the patients with EF≤35% had an implantable cardioverter defibrillator. Clinical follow-up data were obtained for 4090 patients (99.2%). Event rates were higher in patients with low EF (adjusted hazard ratio [95% confidence interval] for EF≤35%, with EF≥60% as reference: 3.93 [2.60-5.93] and 7.12 [3.85-13.18], for all-cause death and cardiovascular death, respectively). CONCLUSIONS: In patients with stable CAD, LVSD is well taken into account by cardiologists, with extensive use of evidence-based medications and interventions. Despite this, LVSD remains a major prognostic indicator in this population.

Angiotensin II receptor blockers versus angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: Prevalence, correlates, and prognostic impact (from the CORONOR study).

BACKGROUND: In international guidelines for patients with stable coronary artery disease (CAD), angiotensin-converting enzyme inhibitors (ACE-I) are recommended while angiotensin II receptor blockers (ARB) are proposed as an alternative in case of intolerance. There are no real-life data on the frequency and correlates of ARB use in this setting. METHODS: We studied 3363 outpatients included in a prospective registry on stable CAD (the CORONOR study) and receiving an ARB or an ACE-I at inclusion. RESULTS: Altogether, 944 patients received an ARB (28.1%). Factors positively and independently associated with ARB use versus ACE-I use were a history of hypertension, the absence of prior myocardial infarction, age, female gender, estimated glomerular filtration rate <60ml/min/m2, and left ventricular ejection fraction ≥40%. In the whole study population, the hazard ratio (HR) for the combined endpoint (cardiovascular death, myocardial infarction, stroke) of patients with ARB use was 0.95 (0.69-1.31) (p=0.765) (patients with ACE-I use as reference). Similar results were observed when the analysis was restricted to a propensity-matched cohort: HR=0.91 (0.62-1.34) (p=0.632). CONCLUSIONS: Our study shows that a significant proportion of stable CAD patients are treated with ARB rather than with ACE-I in modern practice. Several correlates of ARB prescription were identified. Our results suggest that patients receiving ARB have similar outcome than patients receiving ACE-I.

Clopidogrel Use as Single Antiplatelet Therapy in Outpatients with Stable Coronary Artery Disease: Prevalence, Correlates and Association with Prognosis (from the CORONOR Study).

BACKGROUND: Clopidogrel use as single antiplatelet therapy (SAPT) has never been evaluated in stable coronary artery disease (CAD) outpatients either as compared to placebo or aspirin. METHODS: We therefore studied 2,823 outpatients included in a prospective registry. The patients were divided into 2 groups according to their antiplatelet therapy regimen: patients treated with clopidogrel were compared with those treated with aspirin alone. RESULTS: The mean time since CAD diagnosis was 7.9 years. Altogether, 776 (27.5%) patients received clopidogrel as SAPT. Factors independently associated with clopidogrel use were prior aortic or peripheral intervention, drug-eluting stent implantation, stroke, carotid endarterectomy and time since CAD diagnosis. Clopidogrel tended to be used in higher-risk patients: composite of cardiovascular death, myocardial infarction or stroke at 5.8 versus 4.2% (p = 0.056). However, after propensity score matching, similar event rates were observed between the groups: 5.9% when treated with clopidogrel versus 4.4% with aspirin (p = 0.207). The rate of bleeding was also similar between the groups. CONCLUSIONS: Our study shows that a significant proportion of stable CAD patients are treated with clopidogrel as SAPT in modern practice. Several correlates of such an attitude were identified. Our results suggest that this strategy is not beneficial as compared to aspirin alone in terms of ischaemic or bleeding events.

Prevalence and correlates of non-optimal secondary medical prevention in patients with stable coronary artery disease.

BACKGROUND: In patients with coronary artery disease (CAD), non-optimal use of evidence-based medications is associated with an increased risk of adverse outcome. AIMS: To assess the prevalence and correlates of non-optimal secondary medical prevention in patients with stable CAD. METHODS: We included 4184 consecutive outpatients with stable CAD. Treatment at inclusion was classified as optimal/non-optimal regarding the four major classes of secondary prevention drugs: antithrombotics; statins; angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs); and beta-blockers. For each treatment, the prescription was considered non-optimal if the drug was missing despite a class IA indication according to international guidelines. To assess the information globally, non-optimal secondary prevention was defined as at least one major treatment missing. RESULTS: The proportions of patients with non-optimal treatment were 0.7%, 7.8%, 12.9% and 10.3% for antithrombotics, statins, ACE inhibitors/ARBs and beta-blockers, respectively. Non-optimal secondary medical prevention was observed in 16.8% of cases. By multivariable analysis, the correlates of non-optimal secondary medical prevention were long time interval since last coronary event (P<0.0001), older age (P<0.0001), diabetes mellitus (P<0.0001), hypertension (P<0.0001), no history of myocardial infarction (P=0.001), no history of coronary revascularization (P=0.013) and low glomerular filtration rate (P=0.042). CONCLUSIONS: Although most patients with stable CAD are receiving evidence-based medications according to guidelines, there remain subgroups at higher risk of non-optimal treatment. In particular, it might be feasible to improve prevention by focusing on patients in whom a long time has elapsed since the last coronary event.

Secondary medical prevention and clinical outcome in coronary artery disease patients with a history of non-coronary vascular intervention: A report from the CORONOR investigators.

AIM: To assess the level of secondary prevention and the outcome of coronary artery disease (CAD) in patients who have a history of non-coronary vascular intervention. BACKGROUND: Patients with polyvascular disease have been reported to receive less evidence-based medications, with worse risk factor control and to be at higher risk than patients with single-bed disease. It is unknown whether these findings remain valid in the modern era of secondary prevention. METHODS: We included 4184 patients with stable CAD. Two groups were formed according to the absence (n = 3704) or presence (n = 480) of a history of non-coronary vascular intervention. Treatments and risk factor control were recorded at inclusion. Follow-up was performed after 2 years. RESULTS: Antiplatelets, angiotensin system antagonists, beta-blockers and statins were widely prescribed in both groups. The number of antihypertensive drugs was higher in patients with non-coronary vascular intervention. Except for slight increases in the rate of current smokers and in systolic blood pressure, risk factor control was similar between groups. All-cause and cardiovascular mortality rates were higher in patients with non-coronary intervention with adjusted HR of 1.55 (1.13-2.13) (p = 0.007), and 1.98 (1.24-3.15) (p = 0.004), respectively. CONCLUSIONS: In modern practice and real life conditions, the higher risk of CAD patients with a history of non-coronary vascular intervention is taken into account, with more intense secondary prevention and similar risk factor control than patients without such history. In spite of the level of secondary prevention, patients with a history of non-coronary vascular intervention remain at high risk of cardiovascular events. This should be an incentive to discuss more stringent objectives for secondary prevention in patients with polyvascular disease.

Incidence, source, determinants, and prognostic impact of major bleeding in outpatients with stable coronary artery disease.

BACKGROUND: Although there is evidence that patients who experience major bleeding after an acute coronary event are at higher risk of death in the months after the event, the incidence and impact on outcome of bleeding beyond 1 year of follow-up in patients with stable coronary artery disease (CAD) are largely unknown. OBJECTIVES: The goal of this study was to assess the incidence, source, determinants, and prognostic impact of major bleeding in stable CAD. METHODS: We prospectively included 4,184 consecutive CAD outpatients who were free from any myocardial infarction (MI) or coronary revascularization for >1 year at inclusion. Follow-up was performed at 2 years, with major bleeding defined as a type ≥3 bleed using the Bleeding Academic Research Consortium (BARC) definition. RESULTS: There were 51 major bleeding events during follow-up (0.6%/year). Most events were BARC type 3a bleeds with 12 fatal bleeds (type 5). In most cases (54.9%), the site of bleeding was gastrointestinal. Major bleeding was significantly associated with mortality (adjusted hazard ratio: 2.89; 95% confidence intervals: 1.73 to 4.83; p < 0.0001). The increased risk of bleeding associated with vitamin K antagonist (VKA) treatment was particularly evident when VKA was combined with an antiplatelet therapy (APT). In contrast, the risk of cardiovascular death, MI, or nonhemorrhagic stroke did not differ in patients who received VKA + APT versus patients on VKA alone. CONCLUSIONS: In patients with stable CAD (i.e., >1 year, with no acute events), major bleeding events are rare, but such events are an independent predictor of death. When oral anticoagulation is required, concomitant APT should not be prescribed in the absence of a recent cardiovascular event.

Dual antiplatelet therapy in patients with stable coronary artery disease in modern practice: prevalence, correlates, and impact on prognosis (from the Suivi d'une cohorte de patients COROnariens stables en region NORd-Pas-de-Calais study).

BACKGROUND: The prevalence and correlates of dual-antiplatelet therapy (DAPT) use in stable coronary artery disease (CAD) are unknown. In addition, whether prolonged DAPT may impact prognosis in stable CAD has not been studied in real-life conditions. METHODS: We studied 3,691 patients included in a prospective registry on stable CAD. The patients were divided in 2 groups according to their antiplatelet therapy regimen at inclusion: patients treated with DAPT were compared with those treated with single-antiplatelet therapy (SAPT). The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. RESULTS: Altogether, 868 (24%) patients received DAPT. Factors positively associated with DAPT use were persistent angina at inclusion, body mass index, myocardial infarction since 1 to 3 years, myocardial revascularization since 1 to 3 years, multivessel CAD, prior drug-eluting stent implantation, and prior aortic or peripheral intervention. Factors negatively associated with DAPT use were age, prior coronary bypass, and left ventricular ejection fraction. The rate of the primary outcome at 2 years was similar whether patients were treated with SAPT (4.6%) or DAPT (5.5%) (P = .301). Similar rates were also observed after propensity score matching: 5.7% when treated with SAPT versus 5.5% when treated with DAPT (P = .886). The rate of bleeding was similar between groups. CONCLUSIONS: Our study shows that a significant proportion of stable CAD patients are treated with DAPT in modern practice. Several correlates of DAPT were identified. Although no increase in bleeding was observed, our results do not support the prescription of prolonged DAPT.

Prognostic impact of ß-blocker use in patients with stable coronary artery disease.

OBJECTIVE: To assess the association of ß-blocker use with cardiovascular mortality in patients with stable coronary artery disease (CAD). METHODS: We analysed the data of 4184 outpatients included in a prospective cohort study on stable CAD. Two groups were formed based on ß-blocker use at enrolment. Two propensity score analyses were performed to control for differences in covariates: one with adjustment among the entire cohort, and the other with propensity score matching. The outcome variable was cardiovascular mortality after a 2-year follow-up. RESULTS: There were 3320 patients with ß-blocker use. Younger age, hypertension, diabetes, prior myocardial infarction, multivessel CAD, prior coronary revascularisation, prior stroke, prior hospitalisation for heart failure and a low LVEF were associated with ß-blocker use. Clinical follow-up data were obtained for 4149 patients (99.2%). When adjusted on propensity score, ß-blocker use was associated with a HR for cardiovascular mortality of 0.64 (0.42-0.98) in the whole cohort (p=0.04). After one-to-one propensity score matching, both groups (n=839 in each group) were well matched on covariates. The cardiovascular mortality rate in the propensity-matched cohort was significantly lower in patients with ß-blocker use with a HR of 0.43 (0.22-0.82) (p=0.011). Non-cardiovascular mortality was similar in both groups. These results were consistent across different subgroups. CONCLUSIONS: In this observational study of patients with stable CAD, the use of ß-blockers was associated with a lower risk of cardiovascular mortality.