scholarly journals Recent advances in treatment of heart failure

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1475 ◽  
Author(s):  
Takeshi Kitai ◽  
WH Wilson Tang
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
New Drugs ◽  
Significant Progress ◽  
Clinical Endpoints ◽  
Proper Patient Selection ◽  
Treat Heart Failure ◽  
The Us ◽  
Early Phase Clinical Trials ◽  
Study Designs

With the total cases and economic burden of heart failure continuing to rise, there is an overwhelming need for novel therapies. Several drugs for heart failure have succeeded in preclinical and early-phase clinical trials, but most of them failed to show the real benefit in pivotal clinical trials. Meanwhile, the US Food and Drug Administration recently approved two promising new drugs to treat heart failure: ivabradine and sacubitril/valsartan. Furthermore, some of the newer agents in testing offer the potential for significant progress in addition to these drugs. Patiromer and zirconium cyclosilicate are attractive agents that are expected to prevent hyperkalemia during renin-angiotensin-aldosterone system inhibition, and serelaxin and urodilatin are promising drugs in the treatment of acute heart failure. Future clinical trials with more appropriate study designs, optimal clinical endpoints, and proper patient selection are mandatory to assess the true efficacy of these attractive compounds in clinical practice.

scholarly journals Clinical Characteristics of De Novo Heart Failure and Acute Decompensated Chronic Heart Failure: Are They Distinctive Phenotypes That Contribute to Different Outcomes?

2021 ◽  
Vol 7 ◽  
Author(s):  
Wilson Matthew Raffaello ◽  
Joshua Henrina ◽  
Ian Huang ◽  
Michael Anthonius Lim ◽  
Leonardo Paskah Suciadi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Chronic Heart Failure ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
De Novo ◽  
Heart Failure Patients ◽  
Treat Heart Failure ◽  
Patients With Heart Failure ◽  
New Strategies

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.

scholarly journals Inclusion of Older People Reflective of Real‐World Clinical Practice in Cardiovascular Drug Trials

2020 ◽  
Vol 9 (21) ◽  
Author(s):  
Gillian E. Caughey ◽  
Maria C. Inacio ◽  
J. Simon Bell ◽  
Agnes I. Vitry ◽  
Sepehr Shakib
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Older People ◽  
Real World ◽  
Product Information ◽  
Drug Product ◽  
New Drugs ◽  
Efficacy And Safety

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.

Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A 7-Year Experience by the US Food and Drug Administration

2004 ◽  
Vol 22 (22) ◽  
pp. 4626-4631 ◽  
Author(s):  
Lilia Talarico ◽  
Gang Chen ◽  
Richard Pazdur
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
The Elderly ◽  
New Drugs ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Age Related ◽  
The Us

Purpose To analyze the age-related enrollment of cancer patients onto registration trials of new drugs or new indications approved by the US Food and Drug Administration from 1995 to 2002. Patients and Methods This study involved retrospective analyses of demographic data of cancer patients enrolled onto registration trials. The data on 28,766 cancer patients from 55 registration trials were analyzed according to age distributions of ≥ 65, ≥ 70, and ≥ 75 years. The rates of enrollment in each age group for each cancer were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period 1995 to 1999 based on the 2000 US Census. Results The proportions of the overall patient populations aged ≥ 65, ≥ 70, and ≥ 75 years were 36%, 20%, and 9% compared with 60%, 46%, and 31%, respectively, in the US cancer population. Statistically significant under-representation of the elderly (P < .001) was noted in registration trials for all cancer treatment except for breast cancer hormonal therapies. Patients aged ≥ 70 years accounted for most of the under-representation. Conclusion Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population.

Pharmacotherapy of Chronic Heart Failure in the Elderly: A Review of the Evidence

2010 ◽  
Vol 2 ◽  
pp. CMT.S2794
Author(s):  
Toni L. Ripley ◽  
Thomas A. Hennebry
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Older Patients ◽  
The Elderly ◽  
The United States ◽  
Response To Therapy ◽  
Clinical Endpoints ◽  
Age Related ◽  
Prevalent Disease ◽  
To Receive

Heart failure (HF) is a very prevalent disease in the United States and in Europe, with the highest prevalence among older patients. Population estimates suggest substantial growth among the elderly over the next four decades. However, older patients are underrepresented in clinical trials evaluating HF therapies and are less likely to receive the medications shown in these trials to reduce the morbidity and mortality associated with HF. Age-related differences exist in cardiovascular function that may affect disease progression, clinical presentation, and/or response to therapy. Further, medication use in older patients is complicated by physiologic changes in pharmacokinetics and the presence of multiple co-morbidities, which leads to polypharmacy and the related complications. We reviewed the pharmacotherapy clinical trials in HF to review the results specifically in older patients. Trials were included in this review if clinical endpoints were evaluated, if data regarding the participants’ age was reported, and if the intervention studied was in a medication class that is generally recommended for patients with HF by published guidelines. Although some non-randomized data shows benefits of standard therapies may be maintained among patients with HF ≥ 60 years old, the randomized controlled trials that have been published to date showed no benefit and no harm in this group. Cautious HF management among older patients is critical as additional evidence is pursued.

Regulatory Aspects of Vascular Dementia in the United States

2003 ◽  
Vol 15 (S1) ◽  
pp. 293-295 ◽  
Author(s):  
Armando Oliva ◽  
Ranjit Mani ◽  
Russell Katz
Keyword(s):  
Clinical Trials ◽  
Vascular Dementia ◽  
Diagnostic Criteria ◽  
The United States ◽  
Clinical Syndrome ◽  
New Drugs ◽  
The Us ◽  
Significant Interest ◽  
Modifying Effect ◽  
Special Meeting

There is significant interest in the development of new drugs to treat vascular dementia. However, before US approval of new drugs for this entity is possible, certain issues with regulatory implications need to be addressed. Is vascular dementia a distinct clinical syndrome with valid diagnostic criteria? Can this entity be distinguished from Alzheimer's disease (AD) and other causes of dementia? What design features are important for clinical trials in this disorder? The US Food and Drug Administration (FDA) convened a special meeting of the Peripheral and Central Nervous System Advisory Committee in an attempt to answer these questions. The conclusions from this meeting indicate that vascular dementia (VaD) is a pathologically heterogeneous disorder but appears to be reasonably distinguishable from AD dementia. The NINDS-AIREN diagnostic criteria are suitable as entry criteria for vascular dementia trials. Trials should be similar in duration to AD dementia trials and should employ a dual outcome strategy (cognitive + global/functional measures). For drugs that are believed to have a disease-modifying effect, clinical trials should study specific vascular dementia subtypes and would need to employ substantially different designs from those used currently. The term “vascular dementia” may not be entirely appropriate to describe this population.

Emerging Therapies for Acute and Chronic Heart Failure

2016 ◽  
Vol 29 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Sarah Hanigan ◽  
Robert J. DiDomenico
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiovascular Death ◽  
Phase 3 ◽  
Reduced Ejection Fraction ◽  
Emerging Therapies ◽  
Treat Heart Failure ◽  
Novel Drugs ◽  
The Us ◽  
History Of

Although the period from 1953 to 2001 resulted in the approval of more than 30 medications currently used to treat heart failure (HF), few novel drugs have been approved in the last decade. However, the investigational pipeline for HF medications once again appears promising. In patients with chronic heart failure with reduced ejection fraction (HFrEF), ivabradine and valsartan/sucubitril (LCZ696) were recently approved by the US Food and Drug Administration. Both agents have been shown to reduce the risk of cardiovascular death and HF hospitalization. In the treatment of acute HF, serelaxin and ularitide are the farthest along in development. Both agents have demonstrated favorable effects on surrogate end points and preliminary data suggest a possible mortality benefit with serelaxin. Consequently, phase 3 trials are ongoing to evaluate the effect of serelaxin and ularitide on clinical outcomes. Given the poor history of recent investigational acute HF drugs that have advanced to phase 3/4 studies, enthusiasm for both serelaxin and ularitide must be tempered until these trials are completed.

scholarly journals Prostate-Specific Membrane Antigen-Based Therapeutics

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Naveed H. Akhtar ◽  
Orrin Pail ◽  
Ankeeta Saran ◽  
Lauren Tyrell ◽  
Scott T. Tagawa
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Prostate Specific Membrane Antigen ◽  
Prostate Cell ◽  
Drug Conjugates ◽  
The Us ◽  
External Domain ◽  
Early Phase Clinical Trials ◽  
Specific Membrane

Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with177Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.

scholarly journals Amyotrophic lateral sclerosis: pathogenetic mechanisms and new approaches to pharmacotherapy (literature review)

2019 ◽  
Vol 8 (4) ◽  
pp. 12-18
Author(s):  
T. M. Alekseeva ◽  
T. R. Stuchevskaya ◽  
V. S. Demeshonok
Keyword(s):  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
New Drugs ◽  
Significant Progress ◽  
Future Directions ◽  
Loss Of Self ◽  
The World ◽  
Self Service ◽  
Lateral Sclerosis ◽  
Made In

Amyotrophic lateral sclerosis is a neurodegenerative disease, resulting in the loss of self-service and death of the middle-aged and elderly people. In the last 2 decades, significant progress has been made in the study of the pathogenesis of this disease. Two known drugs (riluzole and edaravone) have been approved by the Food and Drug Administration for treatment of amyotrophic lateral sclerosis. The efficacy of these drugs is extremely low, so clinical trials of new drugs are ongoing all over the world. This review discusses the current achievements and future directions of therapy of this disease.

scholarly journals Recent and Upcoming Drug Therapies for Pediatric Heart Failure

2021 ◽  
Vol 9 ◽  
Author(s):  
Karla L. Loss ◽  
Robert E. Shaddy ◽  
Paul F. Kantor
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Clinical Presentation ◽  
Pediatric Population ◽  
Systolic Dysfunction ◽  
Small Sample ◽  
New Drugs ◽  
High Morbidity ◽  
Reduced Ejection Fraction ◽  
Pediatric Heart Failure

Pediatric heart failure (HF) is an important clinical condition with high morbidity, mortality, and costs. Due to the heterogeneity in clinical presentation and etiologies, the development of therapeutic strategies is more challenging in children than adults. Most guidelines recommending drug therapy for pediatric HF are extrapolated from studies in adults. Unfortunately, even using all available treatment, progression to cardiac transplantation is common. The development of prospective clinical trials in the pediatric population has significant obstacles, including small sample sizes, slow recruitment rates, challenging endpoints, and high costs. However, progress is being made as evidenced by the recent introduction of ivabradine and of sacubitril/valsartan. In the last 5 years, new drugs have also been developed for HF with reduced ejection fraction (HFrEF) in adults. The use of well-designed prospective clinical trials will be fundamental in the evaluation of safety and efficacy of these new drugs on the pediatric population. The aim of this article is to review the clinical presentation and management of acute and chronic pediatric heart failure, focusing on systolic dysfunction in patients with biventricular circulation and a systemic left ventricle. We discuss the drugs recently approved for children and those emerging, or in use for adults with HFrEF.

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