Effect of ASA dose doubling versus switching to clopidogrel on plasma inflammatory markers concentration in patients with type 2 diabetes and high platelet reactivity: The AVOCADO study

Background: The aim of the study was to compare the effects of 2 strategies of antiplatelet treatment (i.e., 150 mg ASA vs. 75 mg clpoidogrel) on plasma level of inflammatory markers in type 2 diabetes mellitus (T2DM) patients with high platelet reactivity (HPR).Methods: Study cohort consisted of 304 T2DM patients on chronic ASA therapy (75 mg per day) participating in the Aspirin Versus/Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes (AVOCADO) study. Patients with HPR defined as Platelet Function Analyzer (PFA)-100 collagene/epinephrine closure time (CEPI-CT) < 193 s (n = 80) were randomized to 150 mg of ASA or 75 mg of clopidogrel in 2:3 ratio, respectively. Concentrations of the selected inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, solubleCD40 ligand (sCD40L), and high sensitivity C-reactive protein (hsCRP), were measured and compared in both treatment groups before and after 8 weeks of treatment in both groups.Results: Out of 234 patients included into final analysis, the total of 34.2% (n = 80) patients displayed HPR, of which 14.1% (n = 33) were randomized into 150 mg of ASA group and 20.1% (n = 47) into 75 mg of clopidogrel group. Treatment with clopidogrel was a positive predictor (stepwise multiple regression analysis) of reduction of sCD40L concentration (odds ratio [OR] 4.15; p = 0.013), while treatment with 150 mg ASA was a positive predictor of reduction of IL-6 concentration (OR 4.38; p = 0.033). There was no statistically significant differences between clopidogrel and ASA 150 mg treatment in respect to predictive value for decreased hsCRP concentrations or increased TNF-α concentrations.Conclusions: Increasing the dose of ASA from 75 mg to 150 mg daily or switching ASA 75 mg to clopidogrel 75 mg daily may reduce concentrations of some inflammatory markers (in particular hsCRP, IL-6 and CD40L) in T2DM patients with HPR treated previously with 75 mg of ASA

Association of plasma concentrations of salicylic acid and high on ASA platelet reactivity in type 2 diabetes patients

Background: The objective of this study was to investigate the association between plasmaconcentrations of salicylic acid (SA) and other minor acetylsalicylic acid (ASA) metabolitesand high on ASA platelet reactivity assessed with different methods in type 2 diabetic patients(T2DM).Methods: Study cohort consisted of 293 T2DM patients on chronic ASA therapy. Plateletfunction inhibition was analyzed using measurements of serum thromboxane B2 (S-TxB2),VerifyNow Aspirin and Platelet Function Analyzer (PFA)-100 assays. The concentration of ASAmetabolites in plasma was measured with a high-performance liquid chromatography (HPLC).Results: In logistic regression analysis both ASA dose/kg of body weight and plasma SAconcentration were found to be predictive of S-TxB2 concentrations above 0.72 ng/mL cut-offpoint (OR 16.9, 95% CI 2.29–125.8, p = 0.006 and OR 5.34, 95% CI 2.67–10.68, p < 0.001,respectively). When using the VerifyNow Aspirin Assay, the concentrations of SA were signifi -cantly lower (p = 0.007) in the group with high on ASA platelet reactivity when compared withthe group with normal on ASA platelet reactivity. In logistic regression analysis plasma SAconcentration was found to be predictive of VerifyNow Aspirin Reaction Units (ARU) ≥ 550(OR 3.86, 95% CI 1.86–8.00, p < 0.001).Conclusions: Our study suggests that disturbances of pharmacokinetic mechanisms mightcontribute to lower plasma SA levels, and subsequently incomplete inhibition of thromboxane A2synthesis as measured with S-TxB2 concentrations and increased platelet reactivity measuredwith VerifyNow in T2DM patients

Fifteen-year differences in indications for cardiac resynchronization therapy in international guidelines—insights from the heart failure registries of the European Society of Cardiology

[Abstract] Cardiac resynchronization therapy (CRT) applied to selected patients with heart failure (HF) improves their prognosis. In recent years, eligibility criteria for CRT have regularly changed. This study aimed to investigate the changes in eligibility of real-life HF patients for CRT over the past fifteen years. We reviewed European and North American guidelines from this period and applied them to HF patients from the ESC-HF Pilot and ESC-Long-Term Registries. Taking into consideration the criteria assessed in this study (including all classes of recommendations i.e., class I, IIa and IIb, as well as patients with AF and SR), the 2013 (ESC) guidelines would have qualified the most patients for CRT (266, 18.3%), while the 2015 (ESC) guidelines would have qualified the least (115, 7.9%; p-value for differences between all analyzed papers <0.0001). There were only 26 patients (1.8%) who would be eligible for CRT using the class I recommendations across all of the guidelines. These results demonstrate the variability in recommendations for CRT over the years. Moreover, this data indicates underuse of this form of pacing in HF and highlights the need for more studies in order to improve the outcomes of HF patients and further personalize their management

One-year outcome in patients with heart failure with mid-range ejection fraction hospitalized due to worsening heart failure

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Differences in clinical characteristics and 1-year outcomes of hospitalized patients with heart failure in ESC-HF Pilot and ESC-HF-LT registries

[Abstract] INTRODUCTION The management of heart failure (HF) has changed significantly in recent decades. OBJECTIVES We analyzed the clinical profile, 1‑year outcomes, predictors of mortality, and hospital readmissions in hospitalized patients enrolled in the European Society of Cardiology Heart Failure Pilot Survey (ESC‑HF Pilot) and Heart Failure Long‑Term Registry (ESC‑HF‑LT). PATIENTS AND METHODS The analysis included hospitalized Polish patients from both registries. The primary endpoint was all‑cause death at 1 year, while the secondary endpoint was all‑cause death or hospitalization for worsening HF at 1 year. RESULTS The study included a total of 1415 hospitalized patients (650 from ESC‑HF Pilot; 765 from ESC‑HF‑LT). The primary endpoint occurred in 89 of the 650 patients (13.7%) and in 120 of the 711 patients (16.9%) from ESC‑HF Pilot and ESC‑HF‑LT, respectively (P = 0.11). The secondary endpoint was more frequent in ESC‑HF Pilot than in ESC‑HF‑LT (201 of 509 [39.5%] vs 222 of 663 [33.5%]; P = 0.04). Compared with ESC‑HF Pilot, patients from the ESC‑HF‑LT registry were older and more often had hypertension, atrial fibrillation, peripheral artery disease, and chronic kidney disease, while the incidence of chronic obstructive pulmonary disease was lower. The percentage of patients receiving drugs for HF (diuretics, angiotensin‑converting enzyme inhibitors, angiotensin receptor blockers, β‑blockers, mineralocorticoid receptor antagonists), anticoagulants, cardiac resynchronization therapy, and implantable cardioverter‑defibrillator were higher in the ESC‑HF‑LT group in comparison with the ESC‑HF Pilot group. CONCLUSIONS Patients from the ESC‑HF‑LT registry had a lower risk of death or hospitalization for worsening HF despite the fact that they were older and had more comorbidities. The results might suggest an improvement in physicians’ adherence to the guidelines on the management of HF in the ESC‑HF‑LT registry

Effect of β-blockers on 1-year survival and hospitalizations in patients with heart failure and atrial fibrillation: results from ESC-HF pilot and ESC-HF long-term registry

[Abstract] Introduction The positive effect of β-blocker therapy in patients with heart failure (HF) and atrial fibrillation (AF) has been questioned. Objectives We aimed to assess the effect of β-blockers and heart rate (HR) control on 1-year outcomes in patients with HF and AF. Patients and methods Of the 2019 Polish patients enrolled in ESC-HF Pilot and ESC-HF Long-Term Registry, 797 patients with HF and AF were classified into 2 groups depending on β-blocker use. Additionally, patient survival was compared between 3 groups classified according to HR: lower than 80 bpm, between 80 and 109 bpm, and of 110 bpm or higher. The primary endpoint was all-cause death and the secondary endpoint was all-cause death or HF hospitalization. Results In patients treated with β-blockers, the primary and secondary endpoints were less frequent than in patients not using β-blockers (10.9% vs 25.6%, P = 0.001 and 30.6% vs 44.2%, P = 0.02, respectively). Absence of β-blocker treatment was a predictor of both endpoints in a univariate analysis but remained an independent predictor only of the primary endpoint in a multivariate analysis (hazard ratio for β-blocker use, 0.52; 95% CI, 0.31–0.89; P = 0.02). The primary and secondary endpoints were more frequent in patients with a HR of 110 bpm or higher, but the HR itself did not predict the study endpoints in the univariate analysis. Conclusions β-blocker use might decrease mortality in patients with HF and AF, but it seems to have no impact on the risk of HF hospitalization. An HR of 110 bpm or higher may be related to worse survival in these patients

Diagnosis, clinical course, and 1-year outcome in patients hospitalized for heart failure with preserved ejection fraction (from the Polish Cohort of the European Society of Cardiology Heart Failure Long-Term Registry)

[Abstract] Compared with heart failure (HF) with reduced ejection fraction (HF-REF), the diagnosis of HF with preserved EF (HF-PEF) is more challenging. The aim of the study was to assess the prevalence of HF-PEF among patients hospitalized for HF, to evaluate the pertinence of HF-PEF diagnosis and to compare HF-PEF and HF-REF patients with respect to outcomes. The analysis included 661 Polish patients hospitalized for HF, selected from the European Society of Cardiology (ESC)-HF Long-Term Registry. Patients with an EF of ≥50% were included in the HF-PEF group and patients with an EF of <50% - in the HF-REF group. The primary end point was all-cause death at 1 year. The secondary end point was a composite of all-cause death and rehospitalization for HF at 1 year. HF-PEF was present in 187 patients (28%). Of those 187 patients, mitral inflow pattern was echocardiographically assessed in 116 patients (62%) and classified as restrictive/pseudonormal in 37 patients (20%). Compared with HF-REF subjects, patients with HF-PEF were older, more often female, and had a higher prevalence of hypertension, atrial fibrillation and sleep apnea. Despite lower B-type natriuretic peptide concentrations and lower prevalence of moderate-to-severe mitral regurgitation in patients with HF-PEF, congestive symptoms at admission were as severe as in patients with HF-REF. There were no significant differences in in-hospital mortality between the HF groups. One-year mortality was high in both groups (17% in HF-PEF vs 21% in HF-REF, p = 0.22). There was a trend toward a lower frequency of the secondary end point in the HF-PEF group (32% vs 40%, p = 0.07). In conclusion, in clinical practice, even easily obtainable echocardiographic indexes of diastolic dysfunction are relatively rarely acquired. One-year survival rate of patients with HF-PEF is not significantly better than that of patients with HF-REF

Anemia at hospital admission and its relation to outcomes in patients with heart failure (from the polish cohort of 2 European Society of Cardiology Heart Failure Registries)

[Abstract] Anemia is a commonly observed co-morbidity in heart failure (HF). The aim of the study was to assess prevalence, risk factors for, and effect of anemia on short- and long-term outcomes in HF. The study included 1,394 Caucasian patients hospitalized for HF, with known hemoglobin concentration on hospital admission, participating in 2 HF registries of the European Society of Cardiology (Pilot and Long-Term). Anemia was defined as hemoglobin concentration of <13 g/dl for men and <12 g/dl for women. Primary end points were (1) all-cause death at 1 year and (2) a composite of all-cause death and rehospitalization for HF at 1 year. Secondary end points included inter alia death during index hospitalization. In addition, we investigated the effect of changes in hemoglobin concentration during hospitalization on prognosis. Anemia occurred in 33% of patients. Predictors of anemia included older age, diabetes, greater New York Heart Association class at hospital admission and kidney disease. During 1-year follow-up, 21% of anemic and 13% of nonanemic patients died (p <0.0001). Combined primary end point occurred in 45% of anemic and in 33% of nonanemic patients (p <0.0001). Anemia was strongly predictive of all the prespecified clinical end points in univariate analyses but not in multivariate analyses. Changes in hemoglobin concentration during hospitalization had no effect on 1-year outcomes. In conclusion, anemia was present in 1/3 of patients with HF. Mild-to-moderate anemia seems more a marker of older age, worse clinical condition, and a higher co-morbidity burden, rather than an independent risk factor in HF

The prevalence and association of major ECG abnormalities with clinical characteristics and the outcomes of real-life heart failure patients - Heart Failure Registries of the European Society of Cardiology

[Abstract] Background: Electrocardiogram (ECG) abnormalities increase the likelihood of heart failure (HF) but have low specificity and their occurrence is multifactorial. Aim: This study aimed to investigate the prevalence and association of major ECG abnormalities with clinical characteristics and outcomes in a large cohort of real-life HF patients enrolled in HF Registries (Pilot and Long-Term) of the European Society of Cardiology. Methods: Standard 12-lead ECG containing at least one of the following simple parameters was considered a major abnormality: abnormal rhythm; >100 bpm; QRS ≥120 ms; QTc ≥450 ms; pathological Q-wave; left ventricle hypertrophy; left bundle branch block. A Cox proportional hazards regression model was used to identify predictors of the primary (all-cause death) and secondary (all-cause death or hospitalization for worsening HF) endpoints. Results: Patients with abnormal ECG (1222/1460; 83.7%) were older, more frequently were male and had HF with reduced ejection fraction, valvular heart disease, comorbidities, higher New York Heart Association class, or higher concentrations of natriuretic peptides as compared to those with normal ECG. In a one-year follow-up, the primary and secondary endpoints occurred more frequently in patients with abnormal ECG compared to normal ECG (13.8% vs 8.4%; P = 0.021 and 33.0% vs 24.7%; P = 0.016; respectively). Abnormal rhythm, tachycardia, QRS ≥120 ms, and QTc ≥450 ms were significant in univariable (both endpoints) analyses but only tachycardia remained an independent predictor of the primary endpoint. Conclusions: HF patients with major ECG abnormalities were characterized by worse clinical status and one-year outcomes. Only tachycardia was an independent predictor of all-cause death

Comparative analysis of long-term outcomes of torasemide and furosemide in heart failure patients in heart failure registries of the European Society of Cardiology

[Abstract] Purpose. Current clinical recommendations do not emphasise superiority of any of diuretics, but available reports are very encouraging and suggest beneficial effects of torasemide. This study aimed to compare the effect of torasemide and furosemide on long-term outcomes and New York Heart Association (NYHA) class change in patients with chronic heart failure (HF). Methods. Of 2019 patients enrolled in Polish parts of the heart failure registries of the European Society of Cardiology (Pilot and Long-Term), 1440 patients treated with a loop diuretic were included in the analysis. The main analysis was performed on matched cohorts of HF patients treated with furosemide and torasemide using propensity score matching. Results. Torasemide was associated with a similar primary endpoint (all-cause death; 9.8% vs. 14.1%; p = 0.13) occurrence and 23.8% risk reduction of the secondary endpoint (a composite of all-cause death or hospitalisation for worsening HF; 26.4% vs. 34.7%; p = 0.04). Treatment with both torasemide and furosemide was associated with the significantly most frequent occurrence of the primary (23.8%) and secondary (59.2%) endpoints. In the matched cohort after 12 months, NYHA class was higher in the furosemide group (p = 0.04), while furosemide use was associated with a higher risk (20.0% vs. 12.9%; p = 0.03) of worsening ≥ 1 NYHA class. Torasemide use impacted positively upon the primary endpoint occurrence, especially in younger patients (aged < 65 years) and with dilated cardiomyopathy. Conclusions. Our findings contribute to the body of research on the optimal diuretic choice. Torasemide may have advantageous influence on NYHA class and long-term outcomes of HF patients, especially younger patients or those with dilated cardiomyopathy, but it needs further investigations in prospective randomised trials