Take Home Message
- Initiation of S/V and up‐titration to target dose was achievable within 10 weeks in half of the patients in the endangered post ADHF population besides other disease altering medications remained stable through the end of the 6 month follow up exhibited a 20% improvement in the use.
- Stroke had a substantially stronger impact on mortality that attenuated rapidly over time as compared with MI and bleeding, among ACS patients undergoing PCI.
- In a cohort of elderly patients hospitalized in Internal Medicine and Geriatric wards HF was exceptionally pervasive, specifically in those in very elderly.
- CD93, CDH5, CHI3L1, EPHB4, ICAM2 and JAMA exhibited different patterns as adverse events approach and their temporal patterns strongly forecast clinical effect in CHF patients.
- EMPRISE provides reduction in overall HCRU as well as HF‐related HCRU initiating EMPA compared to DDP4i initiators.
- Among young and middle aged patients, improved prognosis symbolized as an important achievement and attests of complex barriers to progress in elderly patients.
1. Initiation of Sacubitril/Valsartan and Optimisation of Evidence Based Heart Failure Therapies After Hospitalisation for Acute Decompensated Heart Failure: An Analysis of the TRANSITION Study
A new research was presented by Wachter R, on 31st August 2019 at European Society of Cardiology (ESC) in Paris Expo Porte de Versailles, Paris, France. After hospitalisation for acute decompensated HF (ADHF) with reduced ejection fraction (HFrEF), optimisation of chronic heart failure (HF) therapy endures the key strategy to enhance effects. It is challenging to initiate and up-titrate the disease altering therapies in this endangered patient population. This study explained the forms of treatment optimisation including Sacubitril/Valsartan (S/V) in the TRANSITION study. A randomised, open label TRANSITION (NCT02661217) study compared S/V initiation pre vs. post discharge (114 days) in patients admitted for ADHF after haemodynamic stabilisation. The proportion of patients accomplishing 97/103 mg S/V twice daily (bid) at 10 weeks after randomisation was the primary endpoint. As per label, the Up-titration of S/V was done. At each study visit, the accumulation of information on dose of S/V and on the use of concomitant HF medication was done up to week 26.
A total of 493 patients in the pre-discharge arm and 489 patients in the post-discharge arm gained at least one dose of S/V. 24/26 mg bid starting dose was used by 45% of patients in the pred/c arm vs. 44% in the post-discharge arm and 42% vs. 40% were on 49/51 mg S/V bid, respectively after one month of randomisation. 47% of patients had obtained the target dose in the pre-discharge arm vs. 51% in the post-discharge arm on week 10. At the end of the follow-up on 26 weeks, the proportion of patients further improved to 53% in the pre-discharge and 61% in the post-discharge arm on S/V target dose.
The mean dose of S/V was 132 mg in the predischarge arm and 136 mg in the post-discharge arm on week 10, and it was 140 mg and 147 mg at week 26, respectively. Prior to hospital admission, 52% and 54% of the patients gained a beta-blocker (BB) in the pre-discharge and post-discharge group, respectively, and 42% in both arms obtained a mineralcorticoid receptor antagonist (MRA). On the discharge time, 68% and 71%% of the patients gained a BB and 68% and 65% an MRA, in the pre-discharge and post-discharge groups, respectively. At week 10 and week 26, these measures remained stable. The authors concluded that initiation of S/V and up‐titration to target dose was achievable within 10 weeks in half of the patients in the endangered post ADHF population besides other disease altering medications remained stable through the end of the 6 month follow up exhibited a 20% improvement in the use.
2. Incidence and Effects of Stroke, MI and Bleeding on Mortality Among Patients with ACS Undergoing PCI: A Comparative Analysis From the PROMETHEUS Registry
A new research was presented by Chandiramani R, on 1st September 2019 at European Society of Cardiology (ESC) in Paris Expo Porte de Versailles, Paris, France. Stroke exhibits a potentially calamitous complication among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and still its rates are relatively low. Data on the distribution of stroke incidences across time and its overlay with myocardial infarction (MI) and bleeding after PCI is deficient. This research study shows the occurrence and impacts of stroke, MI and bleeding on subsequent mortality in ACS patients undergoing PCI in contemporary clinical practice. Approximately 19,914 patients with ACS who underwent PCI in the PROMETHEUS multicenter observational study were assessed. By using Kaplan Meier (KM) method, calculation of the cumulative stroke incidence at 30 days and 1 year was performed. The distribution of stroke, MI and bleeding over time were compared and the overlay between their occurrences was estimated. By using multivariable Cox regression, predictors of 1 year stroke occurrence were determined. To estimate the individual effects on subsequent mortality, stroke, MI and bleeding were entered as time-updated covariates.
Of 19,914 patients, 244 patients (1.5%) had a stroke within 1 year, 48 patients experienced an MI while another 48 patients experienced a bleeding event. Additionally, within the 1 year follow-up, 14 of these overlapping patients experienced a stroke, MI and bleeding event. As compared to patients who did not have a stroke, patients who sustained a stroke were more likely to have a prior history of cerebrovascular disease, peripheral artery disease, MI and heart failure. Significantly higher mortality risk was observed with patients having stroke as compared to without stroke (adjusted HR 4.84, p<0.0001). However, as compared to beyond 30 days (adjusted HR 1.22; 95% CI: 0.6-2.46, p= 0.58), the association attenuated over time with a much larger effect in the first 30 days of its occurrence (adjusted HR 17.7, p<0.0001). Significantly lower effects of MI and bleeding on subsequent mortality within 30 days of occurrence was observed as compared to stroke (adjusted HR 6.22, p<0.0001; adjusted HR 7.30, p<0.0001, respectively), beyond 30 days, their effects were more sustained on mortality (adjusted HR 2.89, p<0.0001; adjusted HR 3.05, p<0.0001, respectively). The authors concluded that stroke had a substantially stronger impact on mortality that attenuated rapidly over time as compared with MI and bleeding, among ACS patients undergoing PCI. Following PCI for ACS, optimization of modifiable risk factors and medication adherence are essential parts of management of stroke.
3. Heart Failure in Elderly and Very Elderly Hospitalized Patients: An Epidemiological Analysis From the REPOSI Registry
A new research was presented by M Proietti, on 2nd September 2019 at European Society of Cardiology (ESC) in Paris Expo Porte de Versailles, Paris, France. The authors conducted a study to present the epidemiological profile of elderly and very elderly HF patients in terms of prevalence, associated clinical factors, burden of multimorbidity and functional status. The complete cohort of the REgistro POliterapie SIMI (REPOSI) was used to assess the study aims. REPOSI is an Italian Nationwide Registry of elderly hospitalized patients in Internal Medicine and Geriatric wards. HF diagnosis was assessed at hospital admission according to ICD9 code 428.XX. The results observed were that among the 7003 patients originally enrolled, a total of 1095 (15.6%) patients reported a diagnosis of HF at hospital admission. As per increasing age strata, the prevalence of HF progressively increased, up to 26.8% in patients =90.
A logistic regression analysis found that increasing age, body mass index and total cumulative illness rating scale (CIRS) were associated with HF. Furthermore, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease and polypharmacy (=5 drugs) were associated with HF, while liver disease and neoplasm were inversely associated. As per the CIRS severity index and co-morbidity index quartile, HF patients reported more probable values in the most elevated quartile than those without HF (47.4% vs. 26.6%, p<0.001 and 34.4% vs. 18.5%, p<0.001 respectively). According to short blessed test, geriatric depression scale and Barthel index, patients with HF had altogether progressively cognitive impairment and dementia, depression and dependent from others in daily activities than those without HF (all p<0.001). The authors concluded that in a cohort of elderly patients hospitalized in Internal Medicine and Geriatric wards HF was exceptionally pervasive, specifically in those in very elderly. HF was related with a few clinical variables, accentuating a more grounded clinical multifaceted nature. HF patients were increasingly troubled with multimorbidity and demonstrated an impaired functional status.
4. Circulating Biomarkers of Cell Adhesion in Relation to Clinical Outcomes in Patients with Chronic Heart Failure: The BioSHiFT Study
new research was presented by Bouwens E, on 3rd September 2019 at European Society of Cardiology (ESC) in Paris Expo Porte de Versailles, Paris, France. In chronic heart failure (CHF), cardiovascular inflammation and vascular endothelial dysfunction are existing, and in these mechanisms, cellular adhesion molecules are contemplated to play a key role. The temporal patterns of the blood biomarkers entailed could yield additional insights into these processes. This study analysed the prognostic value of the temporal patterns of blood biomarkers of cell adhesion in stable patients with CHF. A total 263 patients were enrolled. In a median of 9 (IQR: 510) serial, trimonthly blood samples were assembled between a median follow-up of 2.2 (IQR: 1.4-2.5) years. 70 patients reached the composite primary endpoint (PE) of cardiovascular mortality, HF hospitalization, heart transplantation and LVAD. All baseline samples were selected for effectiveness, the two samples closest to a PE, and the last sample accessible for event free patients. Thus, twelve biomarkers of cell adhesion were estimated using the Olink Proteomics Cardiovascular III multiplex assay in 567 samples. Correlations among biomarkers and first PE were explored by combining linear mixed effect models and Cox regression (so-called joint model). Patient’s median age was 68 (IQR: 5976) years, with 72% men and 74% patients with NYHA class III. At earlier, levels of CD93 (Complement component C1q receptor), C D H5 (V E cadherin), C H I3L1 (Chitinase-3like protein 1), EPHB4 (Ephrin type-B receptor 4) and JAM-A (Junctional adhesion molecule A) varied at baseline. In patients approaching the PE vs those who remained event free, the average biomarker developments of these markers, and additionally of ICAM-2 (Intercellular adhesion molecule-2), exhibited different patterns . Repeatedly estimated levels of these biomarkers were individually correlated with the PE. Corresponding HRs [95% CI] per 1SD elevation in log2 level (arbitrary unit) were: CD93: 1.85 [1.29-2.70], CDH5: 1.72 [1.23- 2.44], CHI3L1: 2.45 [1.73-3.56], EPHB4: 1.83 [1.33- 2.55], ICAM2: 1.74 [1.24-2.46] and JAMA: 2.07 [1.39- 3.18], adjusted for clinical characteristics (age, sex, diabetes, atrial fibrillation, baseline NYHA class, diuretics, systolic blood pressure and eGFR). CD93, CDH5, CHI3L1, EPHB4, ICAM2 and JAMA exhibited different patterns as adverse events approach and their temporal patterns strongly forecast clinical effect in CHF patients. These findings showed the accumulative value of repeated assessments of biomarkers of cell adhesion in stable patients with CHF.
5. Reduced Healthcare Utilization in Routine Care Initiators of Empagliflozin with and without Heart Failure: Interim Analysis from the EMPagliflozin CompaRative EffectIveness and SafEty (EMPRISE) Study
A new research was presented by Pawar A, on 3rd September 2019 at European Society of Cardiology (ESC) in Paris Expo Porte de Versailles, Paris, France. This research study shows comparison of HCRU among EMPA and dipeptidyl peptidase4 inhibitor (DPP4i) initiators with and without HF history during treatment initiation. In the first two years, HCRU was analyzed following marketing of EMPA as part of EMPRISE, for patients with T2D in routine care in two US commercial and Medicare claims datasets (08/2014-09/2016) as a noninterventional study on the comparative effectiveness, safety and HCRU of EMPA. A 1:1 propensity-score-matched cohort of patients with T2D was identified for 18 years starting with either EMPA or a DPP4i with and without baseline HF, and by using absolute standardized differences, the balance at baseline (period of 365 days) was analysed with 140 covariates including clinical, HCRU, and cost-related covariates. The risk of first all-cause hospitalization, risk of first HHF, risk of first emergency department (ED) visit, hospital length of stay (LOS), HF-related LOS, number of hospital admissions, HF -related hospital admissions, office visits, and ED visits were compared between EMPA and DDP4i initiators. Almost 2,050 pairs with HF and 15,428 pairs without HF in the three datasets with mean follow-up of 5.2 and 5.4 months were recognized following propensity score matching, respectively. All baseline characteristics were well balanced (with aSD<0.1). 65 patients with HF were older, 51% with more commonly female, and 64% patients had CV history as compared to 58%, 46% and 19% with patients without HF history, respectively. The hazard ratio (HR) for first hospitalization was 0.68 (95%CI: 0.56, 0.83) for EMPA initiators with HF, and 0.89 (95%CI: 0.80, 1.00) for initiators without HF as compared to DPP4i initiators. EMPA initiators shows lower risk of HF-related hospitalization and ED visit with prior HF [HR=0.53 (0.38, 0.74) and HR=0.73 (0.58, 0.93), respectively] and without prior HF [HR=0.45 (0.27, 0.73) and HR=0.82 (0.70, 0.95), respectively]. EMPA initiators shows lower number of all hospital admissions [Incidence rate ratio (IRR)=0.59 (0.50, 0.70) and IRR= 0.78 (0.71, 0.85), respectively] and HF-related hospital admissions [IRR=0.49 (0.37, 0.65) and IRR=0.34 (0.22, 0.53), respectively] with and without baseline HF as compared DPP4i initiators. EMPA initiators show lower in-hospital days and HFrelated in-hospital days per member per year (PMPY) in patients with and without HF history as compared to DDP4i initiators. This interim analysis concluded that in both patients with and without heart failure (HF) EMPRISE provides reduction in overall HCRU as well as HF‐related HCRU initiating EMPA compared to DDP4i initiators.
6. Temporal Trends and Patterns in Cause Specific Mortality and Hospitalizations After Incident Heart Failure: A Longitudinal Analysis of 86,000 Individuals
A new research was presented by Conrad N, on 3rd September 2019 at European Society of Cardiology (ESC) in Paris Expo Porte de Versailles, Paris, France. From the past two decades, improvements in heart failure care were observed. Effectiveness of several different treatments in reducing mortality and hospitalizations has been determined by clinical trials and these treatments are increasingly being used in many countries as presented by observational studies. Scarce information is available about the changes reflecting patient outcomes in routine clinical settings. Anonymised electronic health records were utilized that correlates information from primary care, secondary care, and the national death registry to examine 86,000 individuals with newly diagnosed heart failure between 2002 and 2013 in the UK. After diagnosis, in the first year, allcause and cause specific mortality rates and number of hospitalizations were measured. Category specific rate ratios and 95% confidence intervals, adjusting for patients’ age, sex, region, socio-economic status and 17 major co-morbidities were estimated using Poisson regression models.
All-cause mortality rates were 32% high and is insignificantly different over the period of study (adjusted rate ratio (RR) 2013 vs. 2002: 0.94 [0.88, 1]). Overall rates masked diverging trends provide specific outcomes: reduction in cardiovascular mortality (RR: 0.74 [0.68, 0.81]) was neutralized by an increase in non-cardiovascular mortality (RR: 1.28 [1.17, 1.39]), chiefly due to infections and chronic respiratory conditions. Overall mortality was declined among patients under 80 years of age, (RR 2013 vs. 2002: 0.79 [0.71, 0.88]), but not in older age groups (RR 2013 vs. 2002: 0.97 [0.9, 1.06]) as observed in subgroup analyses. Neoplasms (15%), respiratory conditions (12%), and infections (11%) were the major causes of death determined in 2013 after cardiovascular causes (43%). Hospital admissions for heart failure diagnosis within a year were familiar (1.15 hospitalizations per patient-year at risk), changed little over time (RR: 0.96 [0.92, 0.99]), and were broadly (60%) due to noncardiovascular causes.measured was recommended. The authors concluded that the overall mortality and hospitalizations following a new diagnosis of heart failure have changed little over the past decade in spite of increased use of lifesaving interventions. Among young and middle aged patients, improved prognosis symbolized as an important achievement and attests of complex barriers to progress in elderly patients. The deviation from cardiovascular to non‐cardiovascular causes of death recommends that management of correlated co‐morbidities might provide additional opportunities to improve patients’ prognosis.
