Attestation committee
Accreditation committee
Expert committee
Dispositions, instructions
Normative acts
Nomenclature
Institutions
Scientific councils
Seminars
Theses
Scientific advisers
Scientists
Doctoral students
Postdoctoral students
CNAA logo

 română | русский | english

CNAA / Theses / 2008 / June /

Cardioprotecting action of statins in patients with important cardiovascular risk undergoing anthracycline-containing therapy


Author: Anton Elena
Degree:doctor of medicine
Speciality: 14.00.06 - Cardiology and Rheumatology
Year:2008
Scientific adviser: Victoria Ivanov
doctor habilitat, professor, Public Medico-Sanitary Institution Moldavian Institute of Cardiology
Scientific consultant: Ion Corcimaru
doctor habilitat, professor, State University of Medicine and Pharmacy "Nicolae Testemitanu"
Institution:
Scientific council:

Status

The thesis was presented on the 10 June, 2008
Approved by NCAA on the 18 September, 2008

Abstract

Adobe PDF document0.36 Mb / in romanian

Thesis

CZU 616.12-085:615.27.4:615.277.3

Adobe PDF document 0.75 Mb / in romanian
119 pages


Keywords

anthracycline-induced cardiomyopathy, cardioprotection, cardiotoxicity, doxorubicin, chemotherapy, pleiotropia, cardiovascular risk, statins

Summary

This study focused on the evaluation of cardioprotecting effects of pravastatin in patients receiving cardiotoxic anthracycline-containing chemotherapy and in experimental rats models of doxorubicin-induced cardiomyopathy. The results of the present study showed significant disturbances in diastolic and systolic functions of isolated heart, occurred in doxorubicin-treated rats. Simultaneous pravastatin administration resulted in successful preservation of cardiac indexes.

ECG, EchoCG, plasmatic CK-MB activity, blood lipid concentration and chemotherapeutic efficacy in 78 patients with Non-Hodgkin′s lymphoma, treated during 6 months in accordance with CHOP regimen, were carried out. Within the groups without statin administration there were determined typical doxorubicin-induced changes in the cardiac functional indexes. Diastolic dysfunction was developed in ¼ of patients with low risk of cardiac complications (control group). Within the 2nd group (with important cardiovascular risk) were estimated diastolic disturbances progression and left ventricular contractility deterioration. Significant increment in MPI denoted an aggravation. Important melioration of cardiac activity was observed within the 3rd group (with important cardiovascular risk and simultaneous 20 mg/day pravastatin administration): increase in ejection fraction and ejection time, decrease of MPI, twice reduction of diastolic disturbances cases.

Prolonged QT interval due to doxorubicin-containing chemotherapy was found out in both groups without statin co-medication. Number of patients with a pathological interval underwent a twice rise into 2nd group. Within the group receiving pravastatin QTc shortening and interval normalization occurred in ⅔ patients with previous QT abnormalities.

An eloquent increment in plasmatic CK-MB activity was identified in control group after 3 month follow up and after 6 month – into 2nd group. Within the 3rd group a similar dynamic was prevented with pravastatin.

Aggravation or development of cardiovascular pathology was a clinical evidence of anthracycline cardiotoxicity and was estimated in 42,9% of 2nd group patients. Thus, heart failure functional class rose in 31,4% cases. Contrarily, statin co-medication acted upon previous cardiovascular pathology melioration in 21,4% cases. Its hypocholesterolemic effect resulted in significant decrease of total cardiovascular risk in 36% patients of 3rd group. Evaluation of statin influence on chemotherapeutic efficacy did not discover some meaningful evidences.

Considering many recent researches, statin-determined cardiac function melioration in different cardiovascular pathologies was noted. The obtained effectualness is probable based on the pleiotropic actions of statins: antioxidant, antiinflammatory, immunomodulatory, endothelial protection etc., wich are summarized and ensure the cardioprotecting effect of pravastatin in anthracycline-induced cardiotoxicity.