Discontinued Drugs for the Treatment of Cardiovascular Disease from 2016 to 2018

Li, Tingting; Jiang, Sida; Ni, Bingwei; Cui, Qiuji; Qinan, Liu; Zhao, Hongping

doi:10.3390/ijms20184513

Cited by 18 publications

(7 citation statements)

References 59 publications

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“…It is also believed that the administration of rhACE-2 can reduce ang-II levels in the serum by directing the substrate far-away from the related enzyme inhibiting the activation of the ACE-2 receptor and thereby retaining the pulmonary vascular integrity and avoiding ARDS ( Roshanravan et al, 2020 ). APN0l has been reported safe with no immunogenicity and cardiovascular side effects in clinical trials ( Li et al, 2019 ). Recently engineered trimeric ACE-2 variant have also been reported to be anti-SARS-CoV-2 and hence helpful for treating COVID-19 patients ( Xiao et al, 2021 ).…”

Section: Covid-19 Therapeuticsmentioning

confidence: 99%

Wuhan to World: The COVID-19 Pandemic

Kumar

Singh

Kaur

et al. 2021

Front. Cell. Infect. Microbiol.

165

111

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COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family Coronaviridae. It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier relatives, SARS-CoV (~9.5%) and MERS-CoV (~34.4%), the SARS-CoV-2 has been observed to be more infectious and caused higher morbidity and mortality worldwide. As of now, only the knowledge regarding potential transmission routes and the rapidly developed diagnostics has been guiding the world for managing the disease indicating an immediate need for a detailed understanding of the pathogen and the disease-biology. Over a very short period of time, researchers have generated a lot of information in unprecedented ways in the key areas, including viral entry into the host, dominant mutation, potential transmission routes, diagnostic targets and their detection assays, potential therapeutic targets and drug molecules for inhibiting viral entry and/or its replication in the host including cross-neutralizing antibodies and vaccine candidates that could help us to combat the ongoing COVID-19 pandemic. In the current review, we have summarized the available knowledge about the pathogen and the disease, COVID-19. We believe that this readily available knowledge base would serve as a valuable resource to the scientific and clinical community and may help in faster development of the solution to combat the disease.

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Section: Covid-19 Therapeuticsmentioning

confidence: 99%

Wuhan to World: The COVID-19 Pandemic

Kumar

Singh

Kaur

et al. 2021

Front. Cell. Infect. Microbiol.

165

111

View full text Add to dashboard Cite

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“…These findings provide hope for the therapeutic potential of losmapimod and resulted in the enrollment for the phase III LATITUDE-TIMI 60 trial. The primary endpoint, including a significant reduction of cardiovascular death, remained unmet, but in patients with a STEMI with higher age, elevated hs-CRP or chronic kidney disease, the risk of heart failure tended to be reduced (62,63). Further studies evaluating the antifibrotic effects of p38 on negative cardiac outcomes are warranted (see Figure 3).…”

Section: Cardiac Fibrosismentioning

confidence: 99%

The Diagnostic and Therapeutic Value of Multimarker Analysis in Heart Failure. An Approach to Biomarker-Targeted Therapy

Topf

Mirna

Ohnewein

et al. 2020

Front. Cardiovasc. Med.

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Background: Heart failure is a pathophysiological state, which is still associated with high morbidity and mortality despite established therapies. Diverse well-known biomarkers fail to assess the variety of individual pathophysiology in the context of heart failure.Methods: An analysis of prospective, multimarker-specific therapeutic approaches to heart failure based on studies in current literature was performed. A total of 159 screened publications in the field of biomarkers in heart failure were hand-selected and found to be eligible for this study by a team of experts.Results: Established biomarkers of the inflammatory axis, matrix remodeling, fibrosis and oxidative stress axis, as well as potential therapeutic interventions were investigated. Interaction with end organs, such as cardio-hepatic, cardio-renal and cardio-gastrointestinal interactions show the complexity of the syndrome and could be of further therapeutic value. MicroRNAs are involved in a wide variety of physiologic and pathophysiologic processes in heart failure and could be useful in diagnostic as well as therapeutic setting.Conclusion: Based on our analysis by a biomarker-driven approach in heart failure therapy, patients could be treated more specifically in long term with a consideration of different aspects of heart failure. New studies evaluating a multimarker – based therapeutic approach could lead in a decrease in the morbidity and mortality of heart failure patients.

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“…It must be noted that these challenges are faced also by the cardiovascular drugs, which do not contain an advanced delivery system. Among new promising drugs that failed to reach the clinic in the last 5 years was a recombinant apolipoprotein A-I Milano (MDCO-216) discontinued after phase II trials, as well as bococizumab, a humanized monoclonal antibody against PCSK9 developed by Pfizer and losmapimod, an inhibitor of p38 mitogen-activated protein kinases, developed by GSK and discontinued after phase III trials (Li et al, 2019). Although the reasons for discontinuation are diverse, it is clear that the later the phase of development, the higher are the costs of candidate drug's failure.…”

Section: Clinical Safety and Translationmentioning

confidence: 99%

The Grand Challenges in Cardiovascular Drug Delivery

Cicha

2021

Front. Drug. Deliv.

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Despite the ongoing development in invasive cardiovascular interventions and pharmacological therapies over the past 25 years, cardiovascular diseases (CVD) continue to account for 31% of all deaths worldwide. This amounts to 17.9 million deaths per year, a number that is expected to grow to more than 23.6 million by 2030, according to WHO estimates. According to the European Cardiovascular Disease Statistics 2017 (Wilkins et al., 2017), CVD caused 3.9 million deaths in Europe alone. As reported by the 2019 Heart Disease and Stroke Statistics of the American Heart Association (Benjamin et al., 2019), every 40 s, an American will suffer from a myocardial infarction (MI).In the recent years, effective medicines allowed to better control blood cholesterol levels, to lower blood pressure and, finally, to reduce inflammation, which contributed to improved management of patients with CVD. However, the first symptom of CVD in more than 50% cases is acute cardiovascular event or sudden cardiac death. This background calls for more reliable risk assessment allowing earlier disease detection and for improved therapeutic approaches.Atherosclerosis and arterial thrombosis, the underlying causes of cardiovascular morality, can manifest as acute coronary syndromes, stroke or peripheral arterial disease. Drug delivery systems, which enable for example targeted application of medicines should have an enormous impact for the affected patients, as personalized tools to support the physicians in both the choice and the administration of recommended therapies. Among the potential therapeutic targets of novel drug delivery systems and biomaterial implants are vulnerable atherosclerotic plaques, ischemic myocardium, cerebro-, retino-, and renovascular disorders, but also thrombosis. Besides, cardiovascular stents, prostheses and patches can serve as tools for local drug delivery to enhance vascular healing and prevent neoatherosclerosis. The road from the ambitious experimental ideas to the clinical routine remains difficult, however. There are several Grand Challenges that must be addressed to overcome the hurdles for the development of drug delivery systems that will improve the outcomes of patients with CVD. Besides the biggest obstacle, which is the clinical safety and translation, also innovation, personalization and drug delivery on-demand represent major challenges. These challenges are discussed in detail below.

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Discontinued Drugs for the Treatment of Cardiovascular Disease from 2016 to 2018

Cited by 18 publications

References 59 publications

Wuhan to World: The COVID-19 Pandemic

Wuhan to World: The COVID-19 Pandemic

The Diagnostic and Therapeutic Value of Multimarker Analysis in Heart Failure. An Approach to Biomarker-Targeted Therapy

The Grand Challenges in Cardiovascular Drug Delivery

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