Evaluation of antiproliferative efficacy of valsartan in patients with coronary artery disease during myocardial revascularisation (the PROLIV study)

Background. Nowadays coronary artery bypass graft (CABG) surgery is the most widely used treatment option in patients with multivessel coronary artery disease (CAD) including left main artery lesion. The long-term prognosis of these patients is determined by the properties of the grafts. Objective. To investigate antihypertensive and antiproliferative activity of the angiotesin-converting enzyme inhibitor Valsartan (Valz, Actavis Group, Iceland). Design and methods. Sixty CAD patients who underwent CABG surgery, were enrolled. Antihypertensive effects of Valsartan were assessed by 24-hour blood pressure monitoring. Venous specimens were taken during CABG surgery. Morphological changes in saphenous veins were studied by microscopy, histochemistry and immunological methods. Results. Antihypertensive effects of valsartan and perindopril were comparable. The mean systolic and diastolic blood pressure did not differ in valsartan and perindopril groups. No changes between groups were found by morphological methods. Proliferative activity of endothelial cells was significantly lower in valsartan group. Conclusion. Valsartan in CAD patients after CABG surgery is an effective therapeutic approach regarding the prevention of the intimal hyperplasia of venous grafts.

antihypertensive therapy, valsartan, myocardial revascularization, venous grafts, coronary artery bypass graft surgery

1. Бокерия Л.А., Гудкова Р.Г Итоги научных исследований по проблеме сердечно-сосудистой хирургии в 2009 г. // Грудная и сердечно-сосудистая хирургия, 2010. — № 5. — С. 4-10.

2. Акчурин Р.С. Хирургическое лечение ишемической болезни сердца — история и современность // «Микрохирургия в России. 30 лет развития». — М.: ГЭОТАР-Медиа, 2005.

3. Wijeysundera D.N., Beattie D. N., Djanini G. et al. Off-pump coronary artery surgery for reducing mortality and morbidity. Metaanalysis of randomized and observational studies // J. Am. Coll. Cardiol. — 2005. — Vol. 46, № 5. — P. 872-882.

4. Berger A., MacCarthy PA., Siebert U., Carlier S. Long-term patency of internal mammary artery bypass grafts: relationship with preoperative severity of native coronary artery stenosis // Circulation. — 2004. — Vol. 110, № 11, Suppl. 1. — P. 36-40.

5. Yamamoto K., Onoda K., Sawada Y. et al. Locally applied cilostazol suppresses neointimal hyperplasia and medial thickening in a vein graft model // Ann. Thorac. Cardiovasc. Surg. — 2007. — Vol. 13, № 5. — P. 322-330.

6. Blobe G.C., Schiemann W.P., Lodish H.F. Role of transforming growth factor beta in human disease // N. Engl. J. Med. — 2000. — Vol. 342, № 18. — P. 1350-1358.

7. HOPE Study Investigators. The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events // Can. J. Cardiol. — 1996. — Vol. 12, № 2. — P. 127-137.

8. Fox K.M.; EURopean trial On reduction of сardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, doubleblind, placebo-controlled, multicentre trial (the EUROPA study) // Lancet. — 2003. — Vol. 362, № 9386. — P. 782-788.

9. Miceli A., Capoun R., Fino C. et al. Effects of angiotensin-converting enzyme inhibitor therapy on clinical outcome in patients undergoing coronary artery bypass grafting // J. Am. Coll. Cardiol. — 2009. — Vol. 54. — P. 1747-1762.

10. Julius S., Kjeldsen S.E., Weber M. et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine:the VALUE randomised trial // Lancet. — 2004. — Vol. 363, № 9426. — Р. 2022-2031.

11. Cohn J.N., Tognoni G. A randomized trial of the angio-tensin-receptor blocker valsartan in chronic heart failure // N. Engl. J. Med. — 2001. — Vol. 345, № 23. — P. 1667-1675.

12. Pfeffer M.A., McMurray J.J., Velazquez E.J. et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both // N. Engl. J. Med. — 2003. — Vol. 349, № 20. — Р. 1893-1906.

13. Mochizuki S., Dahlof B., Shimizu M. et al. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study):a randomised, open-label, blinded endpoint morbidity-mortality study // Lancet. — 2007. — Vol. 369, № 9571. — Р. 1431-1439.

14. World Sales IMS Data, 2007.

15. Peters S., Gotting B., Trummel M., Rust H., Brattstrom A.. Valsartan for prevention of restenosis after stenting of type B2/C lesions: the VAL-PREST trial // J. Inv. Cardiol. — 2001. — Vol. 13, № 2. — P. 93-97.

16. Peters S., Trummel M., Meyners W., Koehler B., West-ermann K. Valsartan versus ACE inhibition after bare metal stent implantation — results of the VALVACE trial // Int. J. Cardiol. — 2005. — Vol. 98, № 2. — P. 331.