Failure to Launch
The importance of inflammation and inflammatory pathways in atherosclerotic disease and acute coronary syndromes (ACS) is well established. The success of statin therapy rests not only on potently reducing levels of low-density lipoprotein cholesterol, but also on the many beneficial, pleiotropic ef...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-08-01
|
| Series: | JACC: Basic to Translational Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X17301468 |
| _version_ | 1819267808461062144 |
|---|---|
| author | Jennifer A. Rymer, MD, MBA L. Kristin Newby, MD, MHS |
| author_facet | Jennifer A. Rymer, MD, MBA L. Kristin Newby, MD, MHS |
| author_sort | Jennifer A. Rymer, MD, MBA |
| collection | DOAJ |
| description | The importance of inflammation and inflammatory pathways in atherosclerotic disease and acute coronary syndromes (ACS) is well established. The success of statin therapy rests not only on potently reducing levels of low-density lipoprotein cholesterol, but also on the many beneficial, pleiotropic effects statin therapy has on various inflammatory mechanisms in atherosclerotic disease, from reducing endothelial dysfunction to attenuating levels of serum C-reactive protein. Due to the growing awareness of the importance of inflammation in ACS, investigators have attempted to develop novel therapies against known markers of inflammation for several decades. Targeted pathways have ranged from inhibiting C5 cleavage with a high-affinity monoclonal antibody against C5 to inhibiting the activation of the p38 mitogen-activated protein kinase signaling cascades. In each of these instances, despite promising early preclinical and mechanistic studies and phase 2 trials suggesting a potential benefit in reducing post-MI complications or restenosis, these novel therapies have failed to show benefits during large, phase 3 clinical outcomes trials. This review discusses several examples of novel anti-inflammatory therapies that failed to show significant improvement on clinical outcomes when tested in large, randomized trials and highlights potential explanations for why targeted therapies against known markers of inflammation in ACS have failed to launch. |
| first_indexed | 2024-12-23T21:23:03Z |
| format | Article |
| id | doaj.art-d9411ae333864ab1b9aba8dbc2e6f41a |
| institution | Directory Open Access Journal |
| issn | 2452-302X |
| language | English |
| last_indexed | 2024-12-23T21:23:03Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Basic to Translational Science |
| spelling | doaj.art-d9411ae333864ab1b9aba8dbc2e6f41a2022-12-21T17:30:41ZengElsevierJACC: Basic to Translational Science2452-302X2017-08-012448449710.1016/j.jacbts.2017.07.001Failure to LaunchJennifer A. Rymer, MD, MBAL. Kristin Newby, MD, MHSThe importance of inflammation and inflammatory pathways in atherosclerotic disease and acute coronary syndromes (ACS) is well established. The success of statin therapy rests not only on potently reducing levels of low-density lipoprotein cholesterol, but also on the many beneficial, pleiotropic effects statin therapy has on various inflammatory mechanisms in atherosclerotic disease, from reducing endothelial dysfunction to attenuating levels of serum C-reactive protein. Due to the growing awareness of the importance of inflammation in ACS, investigators have attempted to develop novel therapies against known markers of inflammation for several decades. Targeted pathways have ranged from inhibiting C5 cleavage with a high-affinity monoclonal antibody against C5 to inhibiting the activation of the p38 mitogen-activated protein kinase signaling cascades. In each of these instances, despite promising early preclinical and mechanistic studies and phase 2 trials suggesting a potential benefit in reducing post-MI complications or restenosis, these novel therapies have failed to show benefits during large, phase 3 clinical outcomes trials. This review discusses several examples of novel anti-inflammatory therapies that failed to show significant improvement on clinical outcomes when tested in large, randomized trials and highlights potential explanations for why targeted therapies against known markers of inflammation in ACS have failed to launch.http://www.sciencedirect.com/science/article/pii/S2452302X17301468acute coronary syndromeanti-inflammatorydrug targets |
| spellingShingle | Jennifer A. Rymer, MD, MBA L. Kristin Newby, MD, MHS Failure to Launch JACC: Basic to Translational Science acute coronary syndrome anti-inflammatory drug targets |
| title | Failure to Launch |
| title_full | Failure to Launch |
| title_fullStr | Failure to Launch |
| title_full_unstemmed | Failure to Launch |
| title_short | Failure to Launch |
| title_sort | failure to launch |
| topic | acute coronary syndrome anti-inflammatory drug targets |
| url | http://www.sciencedirect.com/science/article/pii/S2452302X17301468 |
| work_keys_str_mv | AT jenniferarymermdmba failuretolaunch AT lkristinnewbymdmhs failuretolaunch |