Cardiovascular Clinical Trialists (CVCT) Forum ? EVOLVE: A major cardiovascular outcomes trial in hemodialysis patients

Title : Cardiovascular Clinical Trialists (CVCT) Forum ? EVOLVE: A major cardiovascular outcomes trial in hemodialysis patientsSpeakers: Chris MIX,Amgen,USA - David WHEELER,London,GBRDiscussant: Ziad MASSY,Boulogne-Billancourt,FRAAbstract : EVOLVE: A major cardiovascular outcomes trial in hemodialysis patients.The extracellular calcium-sensing receptor (CaR) was first described in the parathyroid gland. Recent studies have shown that the CaR is also expressed in cardiomyocytes,peri-vascular nerves of the adventitia,vascular smooth muscle cells,and endothelial cells,but our understanding of its physiological functions in the cardiovascular system remains incomplete. A variety of studies point to a possible role of CaR activity modulation in the control of cardiovascular functions. A decrease in CaSR expression in cardiac and vascular structures has been demonstrated in several pathologies such as chronic kidney disease (CKD) and diabetes,and incriminated in the pathogenesis of the cardiovascular disturbances associated with these disease states. Recent in vitro and in vivo findings highlight the role of allosteric coactivators of the CaR,shown to interfere with the development of uremia-induced vascular calcification. Calcimimetics can prevent the vascular calcification process by controlling not only the uremiainduced secondary hyperparathyroidism,hypercalcemia and hyperphosphatemia,but also by directly modulating the activity of the CaR at the site of the vessel wall and thereby reduce vascular calcium and phosphate deposition. The mechanism(s) of this protective effect against vascular mineralization are under active evaluation. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis demonstrated that in these patients with moderate to severe secondary hyperparathyroidism,cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification. The preliminary results of the Phase 3 EVOLVE(TM) (EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events) trial,which evaluated Sensipar®/Mimpara® (cinacalcet) for the reduction of the risk of mortality and cardiovascular (CV) events among 3,883 patients with secondary hyperparathyroidism (HPT) and chronic kidney disease (CKD) receiving dialysis. The primary endpoint of the study was time to the composite event comprising all-cause mortality or first non-fatal cardiovascular event,including myocardial infarction,hospitalization for unstable angina,heart failure or peripheral vascular event. Although patients in the Sensipar/Mimpara arm experienced numerically fewer composite primary events,the results were not statistically significant,and the trial did not meet its primary endpoint in the intent-to-treat analysis.L'auteur n'a pas transmis de conflit d'intérêt concernant les données diffusées dans cette vidéo ou publiées dans la référence citée.Conférence enregistrée : 9th Global Cardiovascular Clinical Trialists Forum ? Paris 2012 Cardiovascular prevention in chronic kidney disease. New therapeutic options and future opportunities- Cardiovascular events are 10 to 20 fold higher in CKD patients. Heart failure is the main cardiovascular complication that occurs in renal patients. Nearly all CV prevention and heart failure trials excluded patients with moderate to severe CKD. Therefore,the general approach and recommendations for CV prevention in the general population may not be equally effective and completely safe in renal patients.- Renal failure is associated with increased vascular inflammation and oxidative stress linked to development of cardiovascular disease. Nrf-2 (NF-E2-related factor 2) is a regulator of anti-oxidant,anti-inflammatory and detoxification pathways. Intervention trials of the synthetic nrf2/nf?b modulator,bardoloxone methyl,in patients with advanced kidney disease associated with type 2 diabetes,demonstrated improvement of renal function (BEAM trial),suggesting that such agents may have therapeutic benefit in chronic renal failure.- The ongoing BEACON trial assesses the efficacy of bardoxolone methyl relative to placebo in delaying progression to end-stage renal disease and cardiovascular deaths in patients with Stage 4 CKD and type 2 diabetes.- More specifically in chronic hemodialysis patients,results from the very few clinical trials undertaken thus far,including trials on lipid reduction,normalization of hematocrit,and increased dialysis dosage,have been unsuccessful.- New CV prevention opportunities are being investigated in specific trials in CKD and hemodialysis patients.The aim of this workshop is to discuss innovative designs and execution plans of CV prevention trials in CKD as well as the interpretation and implementation of the results of such trials and the approvability - regitrsbaility of potentially new CV prevention in CKD indications.Chairpersons: David GOLDSMITH,London,GBR - Luis RUILOPE,Madrid,ESPRéalisation,production : Canal U/3S et CERIMESKeyword : Cardiovascular Clinical Trialists,Paris,2012,Cardiovascular prevention,Baro-stimulation

Disciplines : Sciences médicales. Médecine
Mots-clés : Cardiovascular Clinical Trialists,Paris,2012,Cardiovascular prevention,Baro-stimulation
Type de document : image en mouvement
Type de ressource : lecture
Niveau : higher education,formation continue
Auteurs ou éditeurs : Ziad MASSY