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Identification de marqueurs phénotypiques et génétiques influençant la réponse au traitement et le pronostic des patients atteints d'insuffisance cardiaque
| Content Provider | Semantic Scholar |
|---|---|
| Author | Denus, Simon De |
| Copyright Year | 2009 |
| Abstract | Many phannacological treatments have been show to reduce the risk of the mortality and morbidity associated with heart failure (HF) including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Nonetheless, the significant interindividual variability that exists in the efficacy and tolerability of these and other drugs used in the treatment of HF makes it difficult for clinicians topredict how a given patient will respond to a drug or will affect his prognosis. The general objective of this thesis is to identify factors associated with the drug response and the prognosis of patients with HF or recipients of a heart transplant in order to explain a portion of this variability and ultimately enable a more individualized approach to patient care. Four specific projects were conducted. The first three aimed to identify factors associated with the response to reninangiotensin-aldosterone (RAAS) inhibitors. In particular, the two first projects consisted of retrospective studies of the Studies of Left Ventricular Dysfunction (SOLVD) which established the efficacy of the ACE inhibitor enalapril in HF. In the first sub-study, we demonstrated that a temporal increase in leucocytes, and particularly neutrophils, was associated with an increased risk of cardiovascular events, irrespective of HF etiology. These inflammatory biomarkers were not influenced by enalapril or useful to predict the efficacy. In the second study, we identified risk factors for hyperkalemia, a frequent and potentially fatal adverse drug reaction of enalapril and other RAAS inhibitors. The third project was a phannacogenetic study which suggested that the AGTRl Al166C genetic polymorphism cou Id modulate the efficacy of the ARB canclesartan. Finally, the last study of this thesis was another phannacogenetic study in which we demonstrated that the CYP3A5*1 allele was independently associated with a nephroprotective effect against calcineurin inhibitor-induced nephrotoxicity in heart transplant recipients. In summary, the work presented in this thesis, which encompassed many aspects related to the treatment of HF patients, have demonstrated that an integrative approach that will include an individual's clinical characteristics, selected phenotypes, their changes, as well genetic polymorphisms may ultimately be useful in individualizing the phannacotherapy of |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/6684/Denus_Simon_de_2009_these.pdf;jsessionid=7DA3454C6A4105DA8BACD16006DFD8E3?sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
