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Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril

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Abstract

Enalapril is effective in the suppression of left ventricular remodeling after acute myocardial infarction (AMI), but the effect of telmisartan is unclear. The consecutive 163 AMI patients underwent primary percutaneous coronary intervention and were randomized to telmisartan (n = 82) or enalapril (n = 81). Left ventriculography was performed in the acute and chronic (6 months) phases. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured by zymography in the acute (days 1, 7, and 14) and chronic (6 months) phases. Plasma pentraxin3 (PTX3), a marker of vascular inflammation, was also measured. There were no adverse effects in the telmisartan group. The analysis of the left ventriculograms in the acute and chronic phases revealed no difference between the two groups. MMP-9 activities at days 7 and 14 and in the chronic phase were decreased compared to that at day 1 in both groups. MMP-2 activity was also decreased in the acute phase, but increased in the chronic phase in both groups. There was no difference in the plasma PTX3 level in the acute phase, but in the chronic phase, PTX3 was significantly lower in telmisartan than in enalapril group (2.6 ± 1.4 vs. 3.2 ± 1.6 ng/ml, p = 0.04). Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalapril in AMI patients. Telmisartan can be an alternative to angiotensin converting enzyme inhibitor in patients with AMI.

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References

  1. The SOLVD Investigators (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 325:293–302

    Article  Google Scholar 

  2. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown RJ Jr, Cuddy TE, Davis BR, Gletman EM, Goldman S, Flaker GC, Klein M, Lamas GA, Packer M, Rouleau J, Rouleau JL, Rutherford J, Wertheimer JH, Hawkins CM (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Result of the survival and ventricular enlargement trial. N Engl J Med 327:669–677

    Article  CAS  PubMed  Google Scholar 

  3. Konstam MA, Kronenberg MW, Rousseauet MF, Undelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, Howe DM, Kilcoyne L, Metherall J, Benedict C, Yusuf S, Pouleur H (1993) Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. Circulation 88:2277–2283

    CAS  PubMed  Google Scholar 

  4. Falkenhahn M, Franke F, Bohle RM, Zhu YC, Stauss HM, Bachmann S, Danilov S, Unger T (1995) Cellular distribution of angiotensin-converting enzyme after myocardial infarction. Hypertension 25:219–226

    CAS  PubMed  Google Scholar 

  5. Hokimoto S, Yasue H, Fujimoto K, Yamamoto H, Nakao K, Kaikita K, Sakata R, Miyamoto E (1996) Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction. Circulation 94:1513–1518

    CAS  PubMed  Google Scholar 

  6. Dickstein K, Kjekshus J, the OPTIMAAL Steering Committee (2002) Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 360:752–760

    Article  CAS  PubMed  Google Scholar 

  7. Onodera H, Matsunaga T, Tamura Y, Maeda N, Higuma T, Sasaki S, Mori Y, Yoshimachi F, Ishizaka H, Hanada H, Osanai T, Okumura K (2005) Enalapril suppresses ventricular remodeling more effectively than losartan in patients with acute myocardial infarction. Am Heart J 150:689

    Article  PubMed  Google Scholar 

  8. Wienen W, Entzeroth M, van Meel JC, Stangier J, Busch U, Ebner T, Schmid J, Lehmann H, Matzek K, Kempthorne-Rawson J, Gladigau V, Hauel NH (2000) A review on telmisartan: a novel, long-acting angiotensin II-receptor antagonist. Neva Press, Branford, pp 127–156

    Google Scholar 

  9. Benson SC, Pershadsignh HA, Cl Ho, Chittiboyina A, Desai P, Pravenec M, Qi N, Wang J, Avery MA, Kurtz TW (2004) Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-γ-modulating activity. Hypertension 43:993–1002

    Article  CAS  PubMed  Google Scholar 

  10. Schupp M, Janke J, Clasen R, Unger T, Kintscher U (2004) Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-γ activity. Circulation 109:2054–2057

    Article  CAS  PubMed  Google Scholar 

  11. The ONTARGET Investigators (2008) Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 358:1547–1559

    Article  Google Scholar 

  12. Pilote L, Abrahamowicz M, Rodrigues E, Eisenberg MJ, Rahme E (2004) Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect? Ann Intern Med 141:102–112

    PubMed  Google Scholar 

  13. Spinale FG, Coker ML, Krombach SR, Mukherjee R, Houck WV, Clair MJ, Kribbs SB, Johnson LL (1999) Matrix metalloproteinase inhibition during the development of congestive heart failure. Effects on left ventricular dimensions and function. Circ Res 85:364–376

    CAS  PubMed  Google Scholar 

  14. Peterson JT, Hallak H, Johnson L, Li H, O’Brien PM, Sliskovic DR, Bocan TMA, Coker ML, Etoh T, Spinale FG (2001) Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure. Circulation 103:2303–2309

    CAS  PubMed  Google Scholar 

  15. Rohde LE, Ducharme A, Arroyo LH, Aikawa M, Sukhova GH, Lopez-Anaya A, McClure KF, Mitchell PG, Libby P, Lee RT (1999) Matrix metalloproteinases inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation 99:3063–3070

    CAS  PubMed  Google Scholar 

  16. Kai H, Ikeda H, Yasukawa H, Kai M, Seki Y, Kuwahara F, Ueno T, Sugi K, Imaizumi T (1998) Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute myocardial infarction. J Am Coll Cardiol 32:368–372

    Article  CAS  PubMed  Google Scholar 

  17. Naito Y, Tsujino T, Lee-Kawabata M, Matsumoto M, Ezumi A, Nakao S, Goda A, Ohyanagi M, Masuyama T (2009) Matrix metalloproteinase-1 and -2 levels are differently regulated in acute exacerbation of heart failure in patients with and without left ventricular systolic dysfunction. Heart Vessels 24:181–186

    Article  PubMed  Google Scholar 

  18. Mastunaga T, Abe N, Kameda K, Hagii J, Fujita N, Onodera H, Kamata T, Ishizaka H, Hanada H, Osanai T, Okumura K (2005) Circulating level of gelatinase activity predits ventricular remodeling in patients with acute myocardial infarction. Int J Cardiol 105:203–208

    Article  Google Scholar 

  19. Munger MA, Johnson B, Amber IJ, Callahan KS, Gilbert EM (1996) Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 77:723–727

    Article  CAS  PubMed  Google Scholar 

  20. Roig E, Orus J, Pare C, Azqueta M, Filella X, Perez-Villa F, Heras M, Sanz G (1998) Serum Interleukin-6 in congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 82:688–690

    Article  CAS  PubMed  Google Scholar 

  21. Orus J, Roig E, Perez-Villa F, Pare C, Azqueta M, Filella X, Heras M, Sanz G (2000) Prognostic value of serum cytokines in patients with congestive heart failure. J Heart Lung Transplant 19:419–425

    Article  CAS  PubMed  Google Scholar 

  22. Shioi T, Matsumori A, Kihara Y, Inoko M, Ono K, Iwanaga Y, Yamada T, Iwasaki A, Matsushima K, Sasayama S (1997) Increased expression of interleukin-1β and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload. Circ Res 81:664–671

    CAS  PubMed  Google Scholar 

  23. Levine B, Kalman J, Mayer L, Fillit HM, Packer M (1990) Elevated circulation levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323:236–241

    Article  CAS  PubMed  Google Scholar 

  24. Matsumori A (2004) Anti-inflammatory therapy for heart failure. Curr Opin Pharmacol 4:171–176

    Article  CAS  PubMed  Google Scholar 

  25. Rolph MS, Zimmer S, Bottazzi B, Garlanda C, Mantovani A, Hansson GK (2002) Production of the long pentraxin PTX3 in advanced atherosclerotic plaques. Arterioscler Thromb Vasc Biol 22:781

    Article  Google Scholar 

  26. Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, Pizzetti F, Maggioni AP, Moccetti T, Metra M, Cas LD, Ghezzi P, Sipe JD, Re G, Olivetti G, Mantovani A, Latini R (2000) PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 102:636–641

    CAS  PubMed  Google Scholar 

  27. Latini R, Maggioni AP, Peri G, Gonzini L, Lucci D, Mocarelli P, Vago L, Pasqualini F, Signorini S, Soldateschi D, Tarli L, Schweiger C, Fresco C, Cecere R, Tognoni G, Mantovani A (2004) Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction. Circulation 110:2349–2354

    Article  CAS  PubMed  Google Scholar 

  28. Kotooka N, Inoue T, Fujimatsu D, Morooka T, Hashimoto S, Hikichi Y, Uchida T, Sugiyama A, Node K (2008) Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening. Atherosclerosis 197:368–374

    Article  CAS  PubMed  Google Scholar 

  29. Suzuki S, Takeishi Y, Niizeki T, Koyama Y, Kitahara T, Sasaki T, Sagara M, Kubota I (2008) Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure. Am Heart J 155:75–81

    Article  CAS  PubMed  Google Scholar 

  30. Kameda K, Matsunaga T, Abe N, Hanada H, Ishizaka H, Ono H, Saitoh M, Fukui K, Fukuda I, Osanai T, Okumura K (2003) Correlation of oxidative stress with the activity of matrix metalloproteinase in patients with coronary artery disease: possible role for left ventricular remodeling. Eur Heart J 24:2180–2185

    Article  CAS  PubMed  Google Scholar 

  31. Kameda K, Matsunaga T, Abe N, Fujiwara T, Hanada H, Fukui K, Fukuda I, Osanai T, Okumura K (2006) Increased pericardial fluid level of matrix metalloproteinase-9 activity in patients with acute myocardial infarction. Possible role in the development of cardiac rupture. Circ J 70:673–678

    Article  CAS  PubMed  Google Scholar 

  32. Fujiwara T, Saito S, Osanai T, Kameda K, Abe N, Higuma T, Yokoyama J, Hanada H, Fukui K, Fukuda I, Okumura K (2008) Decreased plasma and cardiac matrix metalloproteinase activities in patients with coronary artery disease and treated with pravastatin. Eur J Pharmacol 594:146–151

    Article  CAS  PubMed  Google Scholar 

  33. Fujiwara T, Matsunaga T, Kameda K, Abe N, Ono H, Higuma T, Yokoyama J, Hanada H, Osanai T, Okumura K (2007) Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction. Heart Vessels 22:303–309

    Article  PubMed  Google Scholar 

  34. Ge CJ, Lu SZ, Chen YD, Wu XF, Hu SJ, Ji Y (2008) Synergistic effect of amlodipine and atorvastatin on blood pressure, left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia. Heart Vessel 23:91–95

    Article  Google Scholar 

  35. Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM, Valsartan in Acute Myocardial Infarction Trial Investigators (2003) Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 349:1893-906

    Google Scholar 

  36. Antman EM, Hand M, Armstrong PW, Bates ER, Green LA, Halasyamani LK, Hochman JS, Krumholz HM, Lamas GA, Mullany CJ, Pearle DL, Sloan MA, Smith SC (2008) 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 117:296–329

    Article  PubMed  Google Scholar 

  37. Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Unemori EN, Lark MW, Amento E, Libby P (1994) Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 75:181–189

    CAS  PubMed  Google Scholar 

  38. Lindsey M, Wedin K, Brown MD, Keller C, Evans AJ, Smolen J, Burns AR, Rossen RD, Michael L, Entman M (2001) Matrix-dependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischemia/reperfusion. Circulation 103:2181–2187

    CAS  PubMed  Google Scholar 

  39. Schwartz JD, Monea S, Marcus SG, Patel S, Eng K, Galloway AC, Mignatti P, Shamamian P (1998) Soluble factor(s) released from neutrophils activates endothelial cell matrix metalloproteinase-2. J Surg Res 76:79–85

    Article  CAS  PubMed  Google Scholar 

  40. Delanty N, Reilly MP, Pratico D, Lawson JA, McCarthy JF, Wood AE, Ohnishi ST, Fitzgerald DJ, FitzGerald GA (1997) 8-epi PGF2a generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo. Circulation 95:2492–2499

    CAS  PubMed  Google Scholar 

  41. Ohara Y, Peterson TE, Harrison DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91:2546–2551

    Article  CAS  PubMed  Google Scholar 

  42. Lods N, Ferrari P, Frey FJ, Kappeler A, Berthier C, Vogt B, Marti H (2003) Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis. J Am Soc Nephrol 14:2861–2872

    Article  CAS  PubMed  Google Scholar 

  43. Bruemmer D, Collins AR, Noh G, Wang W, Territo M, Arias-Magallona S, Fishbein MC, Blaschke F, Kintscher U, Graf K, Law RE, Hsueh WA (2003) Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest 112:1318–1331

    CAS  PubMed  Google Scholar 

  44. Wang M, Takagi G, Asai K, Resuello RG, Natividad FF, Vatner DE, Vatner SF, Lakatta EG (2003) Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates. Hypertension 1:1308–1316

    Article  Google Scholar 

  45. Fukuda D, Shimada K, Tanaka A, Kusuyama T, Yamashita H, Ehara S, Nakamura Y, Kawarabayashi T, Iida H, Yoshiyama M, Yoshikawa J (2006) Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris. Am J Cardiol 97:175–180

    Article  CAS  PubMed  Google Scholar 

  46. Takagi T, Yamamuro A, Tamita K, Yamabe K, Katayama M, Mizoguchi S, Ibuki M, Tani T, Tanabe K, Nagai K, Shiratori K, Morioka S, Yoshikawa J (2003) Pioglitazone reduced neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study. Am Heart J 46:366

    Article  Google Scholar 

  47. Marx N, Wohrle J, Nusser T, Walcher D, Rinker A, Hombach V, Koenig W, Hoher M (2005) Pioglitazone reduces neointima volume after coronary stent implantation: a randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation 112:2792–2798

    Article  CAS  PubMed  Google Scholar 

  48. Yokoyama J, Higuma T, Tomita H, Abe N, Oikawa K, Fujiwara T, Yokota T, Yokoyama H, Kimura M, Sasaki S, Hanada H, Osanai T, Okumura K (2009) Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril. Int J Cardiol 132:114–120

    Article  PubMed  Google Scholar 

  49. Salio M, Chimenti S, Angelis ND, Molla F, Maina V, Nebuloni M, Pasqualini F, Latini R, Garlanda C, Mantovani A (2008) Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction. Circulation 117:1055–1064

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, 036-8562, Japan

    Takashi Yokota, Tomohiro Osanai, Kenji Hanada, Motoi Kushibiki, Naoki Abe, Koichi Oikawa, Hirofumi Tomita, Takumi Higuma, Jin Yokoyama, Hiroyuki Hanada & Ken Okumura

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  1. Takashi Yokota
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  2. Tomohiro Osanai
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Yokota, T., Osanai, T., Hanada, K. et al. Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril. Heart Vessels 25, 460–468 (2010). https://doi.org/10.1007/s00380-010-0013-4

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