The real world of de novo heart failure: the next frontier for heart failure clinical trials?

2020 ◽  
Vol 22 (10) ◽  
pp. 1786-1789 ◽  
Author(s):  
Muhammad Shahzeb Khan ◽  
Javed Butler ◽  
Stephen J. Greene
2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 62-62
Author(s):  
Jason Hu ◽  
Armen G. Aprikian ◽  
Marie Vanhuyse ◽  
Alice Dragomir

62 Background: Novel hormonal agents (NHAs) such abiraterone (ABI) and enzalutamide (ENZA) have demonstrated similar survival benefits against placebo groups in their respective clinical trials leading to their regulatory approval in both the pre- and post-chemotherapy settings in metastatic castration-resistant prostate cancer (mCRPC). Despite the overall tolerable risk profile, certain signals of cardiovascular toxicity were reported for these agents in clinical trials but little is known about their incidence in clinical practice. The objective was to assess the comparative cardiovascular safety of ABI and ENZA in patients with mCRPC in the real-world. Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. Patients were selected on the basis of having received androgen deprivation therapy prior to initiating a novel hormonal agent (ABI or ENZA) between 2012 and 2016. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary disease, cerebrovascular disease, heart failure, arrhythmia and other cardiovascular causes). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline confounders including pre-existing cardiovascular disease. Results: The cohort comprises 2,183 patients, with 1,773 (81.2%) in the ABI group and 410 (18.8%) in the ENZA group. Before IPTW, mean age of the ENZA group was higher than the ABI group (78 vs 76). There were more ENZA patients with pre-existing arrythmia (ABI: 10.7%, ENZA: 15.1%) and diabetes (ABI: 21.5%, ENZA: 25.1%). Crude incidence rates of cardiovascular-related hospitalization were of 10 events per 100 person-years (PYs) and of 7 events per 100 PYs for the ABI and ENZA groups, respectively. After applying IPTW, all baseline variables were well balanced across both groups with standardized differences < 0.05. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZA group (IPTW-hazard ratio (HR): 1.79, 95% confidence interval (95%CI): 1.04-3.09). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR: 3.02, 95%CI: 1.17-7.78). Conclusions: In our study population, there was a greater risk of cardiovascular-related hospitalizations for ABI users relative to ENZA users, in particular for hospitalization for heart failure. Given the lack of evidence from randomized head-to-head comparisons of both agents, these results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.


2013 ◽  
Vol 168 (3) ◽  
pp. 1859-1865 ◽  
Author(s):  
David Niederseer ◽  
Christoph W. Thaler ◽  
Michaela Niederseer ◽  
Josef Niebauer

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Leszek ◽  
M Zaleska-Kociecka ◽  
D Was ◽  
K Witczak ◽  
K Bartolik ◽  
...  

Abstract Background Heart failure (HF) is the leading cause of death and hospitalization in developed countries. Most of the information about HF is based on selected cohorts, the real epidemiology of HF is scarce. Purpose To assess trends in the real world incidence, prevalence and mortality of all in-and outpatients with HF who presented in public health system in 2009–2018 in Poland. Methods It is a retrospective analysis of 1,990,162 patients who presented with HF in Poland in years 2009–2018. It is a part of nationwide Polish Ministry of Health registry that collects detailed information for the entire Polish population (38,495,659 in 2013) since 2009. Detailed data within the registry were collected since 2013. HF was recorded if HF diagnosis was coded (ICD-10). Results The incidence of HF in Poland fell down from 2013 to reach 127,036 newly diagnosed cases (330 per 100,000 population) in 2018 that equals to 43.6% drop. This decrease was mainly driven by marked reduction in females (p&lt;0.001; Fig. 1A) and HF of ischaemic etiology (HF-IE vs HF-nonIE, Fig. 1B. p&lt;0.001). The HF incidence per 100,000 population decreased across all age groups with the greatest drop in the youngest (Table 1). The prevalence rose by 11.6% to reach 1,242,129 (3233 per 100,000 population) in 2018 with significantly greater increase in females and HF-IE (both p&lt;0.0001, Fig. 1C and D, respectively). The HF prevalence per 100,000 population increased across all age groups except for the 70–79 years old. (Table 1). Mortality increased by 28.5% to reach 142,379 cases (370 per 100,000 population) in 2018. The rise was more pronounced among females (p=0.015, Fig. 1E) and in HF-IE (p&lt;0.001, Fig. 1F). The HF mortality per 100 000 population increased across all age groups, except for the 50–59 subgroup (Table 1). Conclusions Heart failure incidence plummeted in years 2013–2018 in Poland due to drop in newly diagnosed HF-IE. Despite that fact, the prevalence and mortality increased with rising trends in HF-IE. Figure 1. Incidence, prevalence, mortality trends Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The project is co-financed by the European Union from the European Social Fund under the Operational Programme Knowledge Education Development and it is being carried out by the Analyses and Strategies Department of the Polish Ministry of Health


2018 ◽  
Vol 37 (6) ◽  
pp. 491-496
Author(s):  
Gustavo Rodrigues ◽  
António Tralhão ◽  
Carlos Aguiar ◽  
Pedro Freitas ◽  
António Ventosa ◽  
...  

2021 ◽  
Vol 7 ◽  
Author(s):  
Wilson Matthew Raffaello ◽  
Joshua Henrina ◽  
Ian Huang ◽  
Michael Anthonius Lim ◽  
Leonardo Paskah Suciadi ◽  
...  

Heart failure is currently one of the leading causes of morbidity and mortality. Patients with heart failure often present with acute symptoms and may have a poor prognosis. Recent evidence shows differences in clinical characteristics and outcomes between de novo heart failure (DNHF) and acute decompensated chronic heart failure (ADCHF). Based on a better understanding of the distinct pathophysiology of these two conditions, new strategies may be considered to treat heart failure patients and improve outcomes. In this review, the authors elaborate distinctions regarding the clinical characteristics and outcomes of DNHF and ADCHF and their respective pathophysiology. Future clinical trials of therapies should address the potentially different phenotypes between DNHF and ADCHF if meaningful discoveries are to be made.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zoe Quandt ◽  
Laura Trupin ◽  
Michael Evans ◽  
Gabriela Schmajuk ◽  
Mark Stuart Anderson ◽  
...  

Abstract Background: Immune checkpoint inhibitors (CPIs) are being used to effectively treat a growing number of cancers but can cause immune related adverse events (irAE). Thyroid dysfunction is the most common endocrine irAE. A meta-analysis of clinical trials estimated that following CPI exposure, 6.6% will become hypothyroid and 2.9% will have hyperthyroidism1. It is unclear if this reflects the real-world incidence of these irAEs. We used electronic health record (EHR) data to identify patients who developed thyroid dysfunction after CPI to estimate the real-world incidence of these irAEs. Methods: Data were derived from the EHR of a large U.S. academic center. We identified subjects treated with CPIs between 2012 and 2018 and excluded those with thyroid cancer or pre-existing thyroid disease. Thyroid dysfunction was identified as either a TSH &gt; 10, an abnormal free T4 or a prescription for thyroid hormone replacement or anti-thyroid medication. Those with thyroid dysfunction were then categorized as having pre-existing disease or a new-onset thyroid irAE based on the timing of CPI initiation. Logistic regression was used to evaluate the association of thyroid irAE with age, gender, CPI and type of cancer. Results: In total, 1146 individuals without pre-existing thyroid disease that received CPIs were assessed. Pembrolizumab was the most common treatment (45%), followed by nivolumab (20%). Less than 10% of subjects received atezolizumab, durvalumab, ipilimumab monotherapy, combined ipilimumab/nivolumab, or other combinations of CPIs. Melanoma was the most common cancer treated (32%), followed by non-small cell lung cancer (13%). The prevalence of any other cancer was &lt; 10% each. Overall, 19% developed thyroid irAEs. After adjustment for gender and age, the type of cancer was significantly associated with new onset thyroid dysfunction (p=0.01). The rates of thyroid irAEs ranged from 10% in glioblastoma to 40% in renal cell cancer. Although there was no significant association between irAEs and specific CPIs in the overall analysis, thyroid irAEs were more common in subjects who received combined ipilimumab/ nivolumab (31%) compared to pembrolizumab (18%, p=0.03), nivolumab (18%, p&lt;0.01) and ipilimumab (15%, p=0.02). Conclusion: Thyroid irAEs are much more common in real world practice than in clinical trials and there is emerging evidence that certain cancer types incur a higher risk of thyroid irAEs even after adjustment for CPI exposure. Clinicians and patients should be educated about these risks. Future work should focus on exploring the reasons underlying the differing rates of thyroid irAEs among different cancers including effect on cancer outcomes. 1Barroso-Sousa et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens. JAMA Oncol. 2017; 02215: 1–10.


2020 ◽  
Vol 9 (21) ◽  
Author(s):  
Gillian E. Caughey ◽  
Maria C. Inacio ◽  
J. Simon Bell ◽  
Agnes I. Vitry ◽  
Sepehr Shakib

Background Underrepresentation of older people in clinical trials remains. This study aimed to examine the inclusion of older people and associated safety and efficacy reports from clinical trials of new molecular entities for cardiovascular disease indications since commencement of the US Food and Drug Administration Drug Trial Snapshot (DTS) Program. The DTS provides concise information on participants included in clinical trials supporting US Food and Drug Administration approval of new drugs. Methods and Results A cross‐sectional analysis between January 1, 2015 and April 30, 2019 of DTS data including approval date, indication, number of trials and participants, age distribution, efficacy, and safety statements was conducted. Participation‐to‐prevalence ratio (PPR) was used to describe representation of older participants in trials relative to disease population. Efficacy and safety statements regarding age were compared with drug prescribing information. A total of 72 079 participants from 10 DTS reports were identified and 39 625 (55.0%) were aged ≥65 years old. Overall, 63.6% of cardiovascular disease DTS reports were representative of people aged ≥65 years old for specific cardiovascular disease conditions. Underrepresentation was observed in 4 DTS: 2 for heart failure (PPR 0.48 and 0.62), 1 for pulmonary arterial hypertension (PPR 0.72), and 1 for venous thromboembolism (PPR 0.38). Participants in clinical trials for new drugs for the treatment of atrial fibrillation (PPR 0.99 and 1.21) and hypercholesterolemia (PPR 0.84 and 0.97) were reflective of the older population for these diseases. An increased risk of adverse events in older participants was reported in 40% DTS safety statements but no differences were reported in the drug product information. Conclusions Despite the fact that >60% of cardiovascular disease trial participants for new molecular entities included in the DTS program were representative of the older population in real‐world clinical practice, concerns remain for conditions including heart failure or venous thromboembolism. Drug product information safety statements regarding age differences in adverse events were not reflective of trial findings. An increased directive is needed to facilitate the generation of real‐world evidence and appropriate reporting within drug product information for these potentially at‐risk patient populations.


Author(s):  
R S Taylor ◽  
H JN Bethell ◽  
D A Brodie
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