PERTINENT - PERindopril-Thrombosis, InflammatioN, endothelial dysfunction and neurohormonal activation trial: A sub-study of the EUROPA study

Ferrari, Roberto; Arbustini, E.; Blann, A.; Cokkinos, D.; Kluft, C.; de Maat, M. P. M.; Tavazzi, L.; Bertrand, R.; Ferrari, R.; Fox, K.; Remme, W. J.; Simoons, M. L.; Christakos, S.; Cokkinos, D.; Geleris, P.; Gialafos, J.; Kardaras, F.; Karidis, K.; Kelesides, C.; Koliopolos, N.; Pyrgakis, V.; Stamatelopoulos, S.; Stavridis, A.; Syribeis, S.; Vardas, P.; Vassiliadis, J.; Zacharoulis, A.; Zobolos, S.; Manolis, A.; Giannetto, M.; Azzolini, P.; Bellone, E.; Pela, G.; Brunelli, C.; Capponi, E.; Casaccia, M.; Ceci, V.; Corsini, G.; De Luca, I.; De Servi, S.; Guarnerio, M.; Di Pasquale, G.; Fiorentini, C.; Giannuzzi, P.; Giovannini, E.; Sinagra, G. F.; Pettinati, G.; Polimeni, M. R.; Santini, M.; Tantalo, L.; Tavazzi, L.; Vajola, S.; Di Giacomo, U.; Gaddi, O.; Iacono, A.; Riva, S.; Cappucci, A.; Marinoni, G. P.; Inama, G.; Antolini, R.; Celegon, L.; Sanguinetti, M.; Cucchini, F.; Renaldini, E.; Giordano, A.; Papi, S.; Marzilli, M.; Dalla Volta, S.; Volterrani, M.; Portaluppi, Francesco; Lorusso, R.; Di Donato, M.; Colombo, A.; Branzi, A.; Proto, C.; Leghissa, R.; Ferrera, R.; Marques, A. L.; Andrade, C. M. D.; Urena, C. G.; Salcedo, J. M. A.; Garcia, P. A.; Azcarate, J. A.; Martinez, V. B.; Coronado, J. L. B.; Cortada, J. B.; Barmejo, M. P.; Calini, J. S. E.; Horcajo, N. A.; Guerrero, J. J. G.; Lorente, J. L.; Montero, J. M. M.; Romero, P. M.; Mayor, J. L. B.; Lopez, F. N.; Peiro, F. N.; de Ros, J. O.; Mas, J. O.; Valderrama, J. C.; Lopez, D. G.; Sanz, A. S.; Bonnin, S. J.; Simarro, E.; Belsue, F. V.; Caimani, R. B.; Aranda, V. L. G.; Ligorit, A. D.; Cocina, E. G.; Miguel, C. M.; Sanpera, J. M. A.

doi:10.1023/A:1024394610648

BACKGROUND: Markers of thrombosis, inflammation, endothelial dysfunction and neurohumoral activation such as fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A are reported to be linked to the increase of cardiovascular risk for atherosclerosis progression and events in patients with cardiovascular diseases. METHODS: EUROPA is a double blind, placebo-controlled trial on 12,231 patients that evaluates the effect of an angiotensin converting enzyme inhibitor--perindopril--on prevention of cardiovascular events in patients with coronary artery disease. PERTINENT is a sub-study of EUROPA that evaluates (a) in Part A (300 patients): the influence of perindopril vs. placebo on fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A. In addition, NOS expression and induction of apoptosis on human umbilical vein endothelial cells and angiotensin converting enzyme levels are also studied; (b) in Part B (about 1200 patients): the predictive role of plasma levels of C-reactive protein and von Willebrand factor on the occurrence of cardiovascular events. To this end, matched case-control analyses are planned (patients with vs. patients without events). STATUS OF PERTINENT: Blood analyses are in progress in four specialised laboratories: (a) Gaubius Laboratory, Leiden, TNO-PG, The Netherlands; (b) University Department of Medicine, Birmingham, UK; (c) University of Pavia, Italy; (d) Fondazione Salvatore Maugeri, Cardiovascular Research Centre, Gussago, Italy. CONCLUSIONS: The PERTINENT sub-study might help elucidating the phenomena contributing to the pathophysiology of cardiovascular events in patients with coronary artery disease and the role of perindopril in such context.