ABSTRACT
OBJECTIVES: Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking. METHODS: We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns. RESULTS: The study population consisted of 16,944 patients (median age 62 years; 71.3â¯% males) with 6,853 (40.3â¯%) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7â¯%) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex. CONCLUSIONS: Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.
Subject(s)
Acute Coronary Syndrome , Biomarkers , Growth Differentiation Factor 15 , Troponin T , Humans , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Biomarkers/blood , Male , Female , Middle Aged , Aged , Troponin T/blood , Growth Differentiation Factor 15/blood , Troponin I/blood , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Natriuretic Peptide, Brain/blood , Time Factors , Peptide Fragments/bloodABSTRACT
BACKGROUND: Older people less frequently receive invasive coronary angiography (ICA) for NSTEMI than younger patients. We describe care, ICA data, and in-hospital and 30-day outcomes of NSTEMI by age in a contemporary and geographically diverse cohort. METHODS: Prospective cohort study including 2947 patients with NSTEMI from 287 centres in 59 countries, stratified by age (≥75 years, n = 761). Quality of care was evaluated based on 12 guideline-recommended care interventions, and data collected on ICA. Outcomes included in hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding and death, as well as 30-day mortality. RESULTS: Patients aged ≥75 years, compared with younger patients, at presentation had a higher prevalence of comorbidities and oral anticoagulation prescription (22.4% vs 7.6%, p < 0.001). Older patients less frequently received ICA than younger patients (78.6% vs 90.6%, p < 0.001) with the recorded reason more often being advanced age, comorbidities or frailty. Of those who underwent ICA, older patients more frequently demonstrated 3-vessel, 4-vessel and/or left main stem coronary artery disease compared to younger patients (49.7% vs 34.1%, p < 0.001) but less frequently received revascularisation (63.6% vs 76.9%, p < 0.001). Older patients experienced higher rates of in-hospital acute heart failure (15.0% vs 8.4%, p < 0.001) and bleeding (2.8% vs 1.3%, p = 0.006), as well as in-hospital and 30-day mortality (3.4% vs 1.3%, p < 0.001; 4.8% vs 1.7%, p < 0.001; respectively), than younger patients. CONCLUSIONS: Patients aged ≥75 years with NSTEMI, compared with younger patients, less frequently received ICA and guideline-recommended care, and had worse short-term outcomes.
Subject(s)
Coronary Angiography , Non-ST Elevated Myocardial Infarction , Registries , Humans , Aged , Non-ST Elevated Myocardial Infarction/therapy , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/diagnosis , Male , Female , Prospective Studies , Age Factors , Aged, 80 and over , Coronary Angiography/statistics & numerical data , Hospital Mortality , Treatment Outcome , Middle Aged , Comorbidity , Risk Factors , Percutaneous Coronary Intervention/statistics & numerical data , Percutaneous Coronary Intervention/mortality , Time FactorsABSTRACT
BACKGROUND: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). METHODS: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. RESULTS: The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]). CONCLUSIONS: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.
Subject(s)
Acute Coronary Syndrome , Myocardial Infarction , Percutaneous Coronary Intervention , Acute Coronary Syndrome/therapy , Aged , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Double-Blind Method , Factor XIa , Female , Hemorrhage/chemically induced , Humans , Male , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Prasugrel Hydrochloride , Ticagrelor , Treatment OutcomeABSTRACT
BACKGROUND/INTRODUCTION: Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD). However, little is known about alterations to prothrombotic state and platelet reactivity early after smoking cessation following percutaneous coronary interventions (PCI). PURPOSE: We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial, inflammatory and coagulation activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation. METHODS: Smoking patients aged 18 years or older at least 30 days after PCI were recruited and encouraged to quit the habit. At baseline and at 30 days, we measured platelet reactivity with VerifyNow system, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit) and cotinine level. RESULTS: Among 117 patients, 84 patients (72%) at a median age of 60.5 years (40 [interquartile range 30-47] pack-years) completed a 30-day follow-up. At day 30, 30 (35.7%) patients stopped smoking with cotinine level < 50 ng/ml. Baseline characteristics were similar in both groups. In smoking quitters a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs. -6 [-32, 37], p = 0.018), along with a change in P-selectin concentration (-11.82 [-23.62, 1.34] vs. 7.19 [-14.24, 17.19] ng/ml, p = 0.005). Positive correlations was noticed between cotinine and both P-selectin ( r = 0.23, p = 0.045) and CXCL4 (r = 0.27, p = 0.02). CONCLUSION: After smoking cessation in CAD patients following PCI an increase in platelet reactivity and a decrease in P-selectin levels were observed. The risk of thrombotic complications post PCI might be paradoxically enhanced among patients who stopped smoking.
Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Smoking Cessation , Humans , Infant , Platelet Aggregation Inhibitors/therapeutic use , Cotinine , P-Selectin , Percutaneous Coronary Intervention/adverse effects , Blood Platelets , Platelet Function TestsABSTRACT
Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23â¯341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.
Subject(s)
Developed Countries , Developing Countries , Global Health , Heart Failure , Female , Humans , Male , Middle Aged , Causality , Heart Failure/epidemiology , Heart Failure/etiology , Heart Failure/mortality , Heart Failure/therapy , Hospitalization/economics , Hospitalization/statistics & numerical data , Hypertension/complications , Hypertension/epidemiology , Income , Stroke Volume , Global Health/statistics & numerical data , Registries/statistics & numerical data , Developed Countries/economics , Developed Countries/statistics & numerical data , Developing Countries/economics , Developing Countries/statistics & numerical data , AgedABSTRACT
Heart failure (HF) is a clinical syndrome with high morbidity and mortality, and its prevalence is rapidly increasing. Galectin-3 (Gal-3) is an important factor in the pathophysiology of HF, mainly due to its role in cardiac fibrosis, inflammation, and ventricular remodeling. Fibrosis is a hallmark of cardiac remodeling, HF, and atrial fibrillation development. This review aims to explore the involvement of Gal-3 in HF and its role in the pathogenesis and clinical diagnostic and prognostic significance. We report data on Gal-3 structure and molecular mechanisms of biological function crucial for HF development. Over the last decade, numerous studies have shown an association between echocardiographic and CMR biomarkers in HF and Gal-3 serum concentration. We discuss facts and concerns about Gal-3's utility in acute and chronic HF with preserved and reduced ejection fraction for diagnosis, prognosis, and risk stratification. Finally, we present attempts to use Gal-3 as a therapeutic target in HF.
Subject(s)
Galectin 3 , Heart Failure , Humans , Atrial Fibrillation , Heart , Heart Failure/diagnosis , Heart Failure/therapy , PrognosisABSTRACT
BACKGROUND: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. METHODS: We used the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years. RESULTS: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17-1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03-1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21-1.42]; interaction P<0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or IV symptoms (HR, 1.17 [95% CI, 1.14-1.19] and HR, 1.14 [95% CI, 1.12-1.17]; interaction P=0.13) and was a stronger predictor for the composite outcome in New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13-1.17] versus 1.09 [95% CI, [1.07-1.11]; interaction P<0.0001). HR for death was greater in ejection fraction ≥40 versus <40% (HR, 1.23 [95% CI, 1.20-1.26] and HR, 1.15 [95% CI, 1.13-1.17]; interaction P<0.0001). CONCLUSION: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF, and among patients with preserved and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078166.
Subject(s)
Heart Failure/psychology , Quality of Life/psychology , Aged , Female , Heart Failure/mortality , Humans , Male , Survival AnalysisABSTRACT
BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).
Subject(s)
Acute Coronary Syndrome/complications , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Atrial Fibrillation/drug therapy , Percutaneous Coronary Intervention , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Vitamin K/antagonists & inhibitors , Acute Coronary Syndrome/therapy , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Aspirin/adverse effects , Atrial Fibrillation/complications , Double-Blind Method , Drug Therapy, Combination , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Pyrazoles/adverse effects , Pyridones/adverse effectsABSTRACT
Background: The coronavirus disease-2019 (COVID-19) pandemic is surging across Poland, leading to many direct deaths and underestimated collateral damage. We aimed to compare the influence of the COVID-19 pandemic on hospital admissions and in-hospital mortality in larger vs. smaller cardiology departments (i.e., with ≥ 2000 vs. < 2000 hospitalizations per year in 2019). Methods: We performed a subanalysis of the COV-HF-SIRIO 6 multicenter retrospective study including all patients hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, focusing on patients with acute heart failure (AHF) and COVID-19. Results: Total number of hospitalizations was reduced by 29.2% in larger cardiology departments and by 27.3% in smaller cardiology departments in 2020 vs. 2019. While hospitalizations for AHF were reduced by 21.8% and 25.1%, respectively. The length of hospital stay due to AHF in 2020 was 9.6 days in larger cardiology departments and 6.6 days in smaller departments (p < 0.001). In-hospital mortality for AHF during the COVID-19 pandemic was significantly higher in larger vs. smaller cardiology departments (10.7% vs. 3.2%; p < 0.001). In-hospital mortality for concomitant AHF and COVID-19 was extremely high in larger and smaller cardiology departments accounting for 31.3% vs. 31.6%, respectively. Conclusions: During the COVID-19 pandemic longer hospitalizations and higher in-hospital mortality for AHF were observed in larger vs. smaller cardiology departments. Reduced hospital admissions and extremely high in-hospital mortality for concomitant AHF and COVID-19 were noted regardless of department size.
ABSTRACT
BACKGROUND: New randomized, controlled trials have become available on oral P2Y12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. METHODS: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. RESULTS: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. CONCLUSIONS: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.
Subject(s)
Acute Coronary Syndrome/complications , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Thrombosis/etiology , Thrombosis/prevention & control , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/therapy , Cause of Death , Hemorrhage , Humans , Network Meta-Analysis , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Prognosis , Purinergic P2Y Receptor Antagonists/administration & dosage , Purinergic P2Y Receptor Antagonists/adverse effects , Randomized Controlled Trials as Topic , Thrombosis/mortality , Treatment OutcomeABSTRACT
BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL. METHODS: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. AF/AFL events were identified by search of the safety database using MedDRA preferred terms ("atrial fibrillation," "atrial flutter"). RESULTS: Dapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events; 7.8 versus 9.6 events per 1000 patient-years; hazard ratio [HR], 0.81 [95% CI, 0.68-0.95]; P=0.009). The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 [95% CI, 0.58-1.09]; no AF/AFL: HR, 0.81 [95% CI, 0.67-0.98]; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 [95% CI, 0.66-1.04]) versus multiple risk factors (HR, 0.78 [95% CI, 0.62-0.99]; P for interaction 0.72) or a history of HF (HF: HR, 0.78 [95% CI, 0.55-1.11]; No HF: HR, 0.81 [95% CI, 0.68-0.97]; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A1c, body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 [95% CI, 0.64-0.92]; P=0.005). CONCLUSIONS: Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient's previous history of AF, atherosclerotic cardiovascular disease, or HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01730534.
Subject(s)
Atrial Fibrillation/drug therapy , Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Benzhydryl Compounds/pharmacology , Diabetes Mellitus, Type 2/complications , Female , Glucosides/pharmacology , Humans , MaleABSTRACT
BACKGROUND: Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS: We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS: At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04). CONCLUSIONS: In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA-TIMI 61 ClinicalTrials.gov number, NCT02019264 .).
Subject(s)
Anti-Obesity Agents/therapeutic use , Benzazepines/therapeutic use , Cardiovascular Diseases/complications , Hypoglycemia/chemically induced , Obesity/drug therapy , Overweight/drug therapy , Weight Loss/drug effects , Aged , Anti-Obesity Agents/adverse effects , Aortic Valve Insufficiency/chemically induced , Benzazepines/adverse effects , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/complications , Double-Blind Method , Female , Follow-Up Studies , Humans , Hypertension, Pulmonary/chemically induced , Male , Middle Aged , Obesity/complications , Overweight/complications , Risk FactorsABSTRACT
BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.
Subject(s)
Atrial Fibrillation/blood , Coronary Disease/blood , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Body Mass Index , Coronary Disease/drug therapy , Double-Blind Method , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Risk Factors , Sedentary Behavior , Sex FactorsABSTRACT
AIMS: PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. METHODS AND RESULTS: This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76). CONCLUSION: Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. CLINICALTRIALS.GOV IDENTIFIER: NCT01225562.
Subject(s)
Myocardial Infarction , Purinergic P2Y Receptor Antagonists , Adenosine/therapeutic use , Drug Therapy, Combination , Humans , Myocardial Infarction/drug therapy , Myocardial Infarction/prevention & control , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Secondary Prevention , Ticagrelor/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: In patients with stable coronary heart disease, it is not known whether achievement of standard of care (SOC) targets in addition to evidence-based medicine (EBM) is associated with lower major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, and stroke. METHODS: EBM use was recommended in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY trial. SOC targets were blood pressure (BP) <140/90â¯mm Hg and low-density lipoprotein-cholesterol (LDL-C)â¯<100 mg/dL and <70 mg/dL. In patients with diabetes, glycosylated hemoglobin A1c (HbA1c)â¯<â¯7% and BP of <130/80 mm Hg were recommended. Feedback to investigators about rates of EBM and SOC was provided regularly. RESULTS: In 13,623 patients, 1-year landmark analysis assessed the association between EBM, SOC targets, and MACE during follow-up of 2.7â¯years (median) after adjustment in a Cox proportional hazards model. At 1â¯year, aspirin was prescribed in 92.5% of patients, statins in 97.2%, ß-blockers in 79.0%, and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers in 76.9%. MACE was lower with LDL-Câ¯<â¯100 mg/dL (70-99 mg/dL) compared with LDL-Câ¯≥â¯100 mg/dL (hazard ratio [HR] 0.694, 95% CI 0.594-0.811) and lower with LDL-Câ¯<â¯70 mg/dL compared with LDL-Câ¯<â¯100 mg/dL (70-99 mg/dL) (HR 0.834, 95% CI 0.708-0.983). MACE was lower with HbA1c <â¯7% compared with HbA1câ¯≥â¯7% (HR 0.705, 95% CI 0.573-0.866). There was no effect of BP targets on MACE. CONCLUSIONS: MACE was lower with LDL-Câ¯<â¯100 mg/dL (70-99 mg/dL) and even lower with LDL-Câ¯<â¯70 mg/dL. MACE in patients with diabetes was lower with HbA1c < 7%. Achievement of targets is associated with improved patient outcomes.
Subject(s)
Cholesterol, LDL/blood , Coronary Disease/blood , Glycated Hemoglobin/analysis , Myocardial Infarction/etiology , Stroke/etiology , Aged , Coronary Disease/complications , Coronary Disease/mortality , Evidence-Based Medicine , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/epidemiology , Risk Factors , Stroke/epidemiologyABSTRACT
The goal of the global congestive heart failure (G-CHF) registry is to collect comparative international data on heart failure characteristics, management, and outcomes and to better understand the determinants that impact the clinical course of heart failure. METHODS: G-CHF is a multicenter, prospective cohort study of adult patients with a new or prior clinical diagnosis of heart failure. We have enrolled 23,047 participants from 257 centers in 40 countries from 8 major geographic regions of the world, with recruitment ongoing. Approximately 4,000 participants will also participate in substudies to assess frailty, comorbidity, diet, barriers to care, biomarkers, and planned detailed echocardiographic analyses. Follow-up is planned for a period of 5â¯years. The primary outcome is cause-specific mortality. Key secondary outcomes include hospitalizations, quality of life, and major cardiovascular and noncardiovascular outcomes. A total of 31.9% of participants were enrolled as inpatients. Thus far, mean age of the cohort at baseline is 63.1â¯years, and 60.8% are male. Participants most commonly have heart failure with reduced ejection fraction (53.6%) followed by preserved ejection fraction (24.2%) and midrange ejection fraction (20.6%). The most common causes of heart failure are ischemic (37.8%) followed by hypertensive (20.0%), idiopathic (15.1%), and valvular disease (8.8%). CONCLUSION: G-CHF will provide a greater understanding of the characteristics of the global heart failure population, variations in its management, clinical outcomes, and what continues to impact morbidity and mortality in this high-risk population.
Subject(s)
Heart Failure/diagnosis , Heart Failure/therapy , Registries , Research Design , Adult , Humans , International Cooperation , Multicenter Studies as Topic , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Premature coronary artery disease is one of the most pressing global issues in modern cardiology. The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients aged < 50 years with myocardial infarction (MI) compared to that in patients aged ≥50 years with MI and to that in young people without MI (no-MI < 50). METHODS: The studied group (MI < 50) consisted of 240 patients aged 26-49 years with MI. The control groups consisted of 240 patients (MI ≥ 50) with MI aged 50-92 years and 240 healthy people aged 30-49 years without a history of MI (no-MI < 50). RESULTS: There were statistically significant differences between the MI < 50 and MI ≥ 50 and no-MI < 50 groups regarding the family history of premature MI/ischaemic stroke and the percentage of patients with ≥2 relatives affected (10.8, 2.9, and 3.7%, respectively; p < 0.0001). There was a statistically significant difference in the patient age at the first MI occurrence among patients without a family history of premature CVD, those with 1 affected relative, and those with ≥2 affected first-degree relatives (56.6, 48.6 and 41.8 years, respectively) as well as those with affected first- and second-degree relatives (56.5, 50.7 and 47.0 years, respectively). CONCLUSIONS: A younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature MI/ischaemic stroke. Thus, the family history of premature atherosclerosis involving not only first- but also second-degree relatives seems to be a valuable factor in CVD risk evaluation in young people.
Subject(s)
Coronary Artery Disease/epidemiology , Family , Myocardial Infarction/epidemiology , Adult , Age of Onset , Aged , Aged, 80 and over , Case-Control Studies , Comorbidity , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/genetics , Female , Heart Disease Risk Factors , Humans , Incidence , Male , Medical History Taking , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/genetics , Pedigree , Poland/epidemiology , Prevalence , Risk Assessment , Smoking/adverse effects , Smoking/epidemiologyABSTRACT
AIMS: The provision of high-quality education allows the European Society of Cardiology (ESC) to achieve its mission of better cardiovascular practice and provides an essential component of translating new evidence to improve outcomes. METHODS AND RESULTS: The 4th ESC Education Conference, held in Sophia Antipolis (December 2016), brought together ESC education leaders, National Directors of Training of 43 ESC countries, and representatives of the ESC Young Community. Integrating national descriptions of education and cardiology training, we discussed innovative pathways to further improve knowledge and skills across different training programmes and health care systems. We developed an ESC roadmap supporting better cardiology training and continued medical education (CME), noting: (i) The ESC provides an excellent framework for unbiased and up-to-date cardiovascular education in close cooperation with its National Societies. (ii) The ESC should support the harmonization of cardiology training, curriculum development, and professional dialogue and mentorship. (iii) ESC congresses are an essential forum to learn and discuss the latest developments in cardiovascular medicine. (iv) The ESC should create a unified, interactive educational platform for cardiology training and continued cardiovascular education combining Webinars, eLearning Courses, Clinical Cases, and other educational programmes, along with ESC Congress content, Practice Guidelines and the next ESC Textbook of Cardiovascular Medicine. (v) ESC-delivered online education should be integrated into National and regional cardiology training and CME programmes. CONCLUSION: These recommendations support the ESC to deliver excellent and comprehensive cardiovascular education for the next generation of specialists. Teamwork between international, national and local partners is essential to achieve this objective.
Subject(s)
Cardiology , Education, Medical, Continuing/organization & administration , Societies, Medical/organization & administration , Cardiology/education , Cardiology/organization & administration , Europe , Humans , Practice Guidelines as TopicABSTRACT
BACKGROUND: Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease. METHODS: Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results. RESULTS: In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]). CONCLUSIONS: The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.
Subject(s)
Benzaldehydes/therapeutic use , Coronary Disease/drug therapy , Coronary Disease/mortality , Myocardial Infarction/epidemiology , Oximes/therapeutic use , Phospholipase A2 Inhibitors/therapeutic use , Stroke/epidemiology , Angina, Unstable/epidemiology , Coronary Disease/complications , Endpoint Determination , Heart Failure/epidemiology , Hospitalization/statistics & numerical data , Humans , Ischemic Attack, Transient/epidemiology , Ischemic Attack, Transient/etiology , Kaplan-Meier Estimate , Myocardial Infarction/etiology , Myocardial Infarction/mortality , Percutaneous Coronary Intervention/statistics & numerical data , Placebos/therapeutic use , Stroke/etiology , Stroke/mortalityABSTRACT
Diabetes mellitus (DM) and abnormal glucose metabolism are associated with cardiovascular (CV) disease. We investigated the prevalence and prognostic importance of dysglycaemia in patients with acute coronary syndromes (ACS) in the PLATelet inhibition and patient Outcomes (PLATO) trial. Diabetes was defined as known diabetes or HbA1c ≥ 6.5% or non-fasting glucose ≥ 11.1 mmol/L on admission, prediabetes as HbA1c ≥ 5.7% but < 6.5%, and no diabetes as HbA1c < 5.7%. The primary endpoint was the composite of CV death, spontaneous myocardial infarction type 1 (sMI) or stroke at 12 months. Multivariable Cox regression models, adjusting for baseline characteristics, and biomarkers NT-proBNP and troponin I, were used to explore the association between glycaemia and outcome. On admission, 16,007 (86.1%) patients had HbA1c and/or glucose levels available and were subdivided into DM 38.5% (6160) (1501 patients had no previous DM diagnosis), prediabetes 38.8% (6210), and no DM 22.7% (3637). Kaplan Meier event rates at 12 months for CV death, sMI or stroke per subgroups were 14.5% (832), 9.0% (522), and 8.5% (293), respectively with multivariable adjusted HRs, versus no diabetes, for diabetes: 1.71 (1.50-1.95) and for prediabetes 1.03 (0.90-1.19). Corresponding event rates for CV death were 6.9% (391), 3.4% (195) and 3.0% (102), respectively, with adjusted HRs for patients with DM of: 1.92 (1.42-2.60) and for prediabetes 1.02 (0.79-1.32). Abnormal glucose metabolism is common in ACS patients, but only patients with definite DM have an increased CV risk, indicating that prediabetes is not immediately associated with worse CV outcomes.