Clinical Research in Cardiology

, Volume 99, Issue 12, pp 787–794

Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease

  • A. R. Zankl
  • B. Ivandic
  • M. Andrassy
  • H. C. Volz
  • U. Krumsdorf
  • E. Blessing
  • H. A. Katus
  • C. P. Tiefenbacher
Original Paper



Peripheral artery disease (PAD) is associated with high cardiovascular mortality and a poor quality of life. The AT1-receptor blocker telmisartan has been shown to have pleiotropic effects and it may also improve endothelial function. The aim of this study was to analyze the effects of telmisartan on absolute walking distance (WD) and endothelial function in patients with PAD.


In a single centre, single-blinded, prospective study, 36 patients with PAD at stage Fontaine II or higher and mild to moderate arterial hypertension were treated with telmisartan 40/80 mg once daily or placebo for 12 months. Primary endpoint was the improvement of the absolute treadmill WD. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT), ankle-brachial index (ABI) and disease-related quality of life (DRQL) were examined as well.


After 12 months, maximum WD increased by 26% in the telmisartan group (P < 0.001). However, in the placebo group it was comparable to baseline. FMD rose by 40% in the telmisartan group while it deteriorated in the placebo group (P < 0.001). IMT and ABI were comparable in both groups at baseline and did not change considerably after 12 months. In non-diabetic patients (72.2%), the ABI did not change in the placebo group, whereas it increased by 11% in the telmisartan group (P < 0.001). While the DRQL remained stable in the telmisartan group, placebo treatment was associated with a marked deterioration (P < 0.01).


Telmisartan improves WD and endothelial function, the ABI in non-diabetic patients and it may prevent further loss of quality of life in patients with advanced PAD.


Endothelial dysfunction Peripheral artery disease Angiotensin receptor blockade Atherosclerosis 


  1. 1.
    O’Hare AM, Katz R, Shlipak MG, Cushman M, Newman AB (2006) Mortality and cardiovascular risk across the ankle-arm index spectrum: results from the Cardiovascular Health Study. Circulation 113:388–393CrossRefPubMedGoogle Scholar
  2. 2.
    Tiefenbacher CP, Bleeke T, Vahl C, Amann K, Vogt A, Kubler W (2000) Endothelial dysfunction of coronary resistance arteries is improved by tetrahydrobiopterin in atherosclerosis. Circulation 102:2172–2179PubMedGoogle Scholar
  3. 3.
    Yiginer O, Ozcelik F, Inanc T, Aparci M, Ozmen N, Cingozbay BY, Kardesoglu E, Suleymanoglu S, Sener G, Cebeci BS (2008) Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome. Clin Res Cardiol 97:334–340CrossRefPubMedGoogle Scholar
  4. 4.
    Daiber A, Wenzel P, Oelze M, Munzel T (2008) New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance. Clin Res Cardiol 97:12–20CrossRefPubMedGoogle Scholar
  5. 5.
    Mollnau H, Wendt M, Szocs K, Lassegue B, Schulz E, Oelze M, Li H, Bodenschatz M, August M, Kleschyov AL, Tsilimingas N, Walter U, Forstermann U, Meinertz T, Griendling K, Munzel T (2002) Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 90:E58–E65CrossRefPubMedGoogle Scholar
  6. 6.
    Higashi Y, Sasaki S, Nakagawa K, Ueda T, Yoshimizu A, Kurisu S, Matsuura H, Kajiyama G, Oshima T (2000) A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study. J Am Coll Cardiol 35:284–291CrossRefPubMedGoogle Scholar
  7. 7.
    Mancini GB, Henry GC, Macaya C, O’Neill BJ, Pucillo AL, Carere RG, Wargovich TJ, Mudra H, Luscher TF, Klibaner MI, Haber HE, Uprichard AC, Pepine CJ, Pitt B (1996) Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation 94:258–265PubMedGoogle Scholar
  8. 8.
    Schmieder RE, Schrader J, Zidek W, Tebbe U, Paar WD, Bramlage P, Pittrow D, Bohm M (2007) Low-grade albuminuria and cardiovascular risk: what is the evidence? Clin Res Cardiol 96:247–257CrossRefPubMedGoogle Scholar
  9. 9.
    Morimoto S, Yano Y, Maki K, Sawada K (2006) Renal and vascular protective effects of telmisartan in patients with essential hypertension. Hypertens Res 29:567–572CrossRefPubMedGoogle Scholar
  10. 10.
    Schmieder RE, Delles C, Mimran A, Fauvel JP, Ruilope LM (2007) Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes. Diabetes Care 30:1351–1356CrossRefPubMedGoogle Scholar
  11. 11.
    Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115:1285–1295PubMedGoogle Scholar
  12. 12.
    Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF (1995) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319PubMedGoogle Scholar
  13. 13.
    Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:7–17CrossRefPubMedGoogle Scholar
  14. 14.
    Fowkes FG (1988) The measurement of atherosclerotic peripheral arterial disease in epidemiological surveys. Int J Epidemiol 17:248–254CrossRefPubMedGoogle Scholar
  15. 15.
    Osmundson PJ, O’Fallon WM, Clements IP, Kazmier FJ, Zimmerman BR, Palumbo PJ (1985) Reproducibility of noninvasive tests of peripheral occlusive arterial disease. J Vasc Surg 2:678–683CrossRefPubMedGoogle Scholar
  16. 16.
    Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG (2007) Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 45(Suppl S):S5–S67CrossRefPubMedGoogle Scholar
  17. 17.
    Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Fatar M, Hernandez Hernandez R, Jaff M, Kownator S, Prati P, Rundek T, Sitzer M, Schminke U, Tardif JC, Taylor A, Vicaut E, Woo KS, Zannad F, Zureik M (2007) Mannheim carotid IMT consensus (2004–2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis 23:75–80Google Scholar
  18. 18.
    Bullinger M, Cachovan M, Creutzig A, Diehm C, Gruss J, Heidrich H, Kirchberger I, Loeprecht H, Rogatti W (1996) Development of an illness-specific instrument for assessment of quality of life in patients with arterial occlusive disease (Peripheral Arterial Occlusive Disease 86 Questionnaire). Vasa 25:32–40PubMedGoogle Scholar
  19. 19.
    Benndorf RA, Appel D, Maas R, Schwedhelm E, Wenzel UO, Boger RH (2007) Telmisartan improves endothelial function in patients with essential hypertension. J Cardiovasc Pharmacol 50:367–371CrossRefPubMedGoogle Scholar
  20. 20.
    Wassmann S, Hilgers S, Laufs U, Bohm M, Nickenig G (2002) Angiotensin II type 1 receptor antagonism improves hypercholesterolemia-associated endothelial dysfunction. Arterioscler Thromb Vasc Biol 22:1208–1212CrossRefPubMedGoogle Scholar
  21. 21.
    Warnholtz A, Ostad MA, Heitzer T, Thuneke F, Frohlich M, Tschentscher P, Schwedhelm E, Boger R, Meinertz T, Munzel T (2007) AT1-receptor blockade with irbesartan improves peripheral but not coronary endothelial dysfunction in patients with stable coronary artery disease. Atherosclerosis 194:439–445CrossRefPubMedGoogle Scholar
  22. 22.
    Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R (2002) Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol 40:505–510CrossRefPubMedGoogle Scholar
  23. 23.
    Sasamura H, Kitamura Y, Nakamura M, Ryuzaki M, Saruta T (2006) Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension. Clin Exp Hypertens 28:511–520CrossRefPubMedGoogle Scholar
  24. 24.
    Schindler C, Mueller A, Bramlage P, Boecking W, Kirch W, Schweizer J (2007) Comparison of selective AT1-receptor blockade versus ACE inhibition for restenosis prophylaxis in patients with peripheral occlusive arterial disease after stent angioplasty: a randomized, controlled, proof-of-concept study. Angiology 58:710–716CrossRefPubMedGoogle Scholar
  25. 25.
    Petrovic I, Petrovic D, Vukovic N, Zivanovic B, Dragicevic J, Vasiljevic Z, Babic R (2005) Ventricular and vascular remodelling effects of the angiotensin II receptor blocker telmisartan and/or the angiotensin-converting enzyme inhibitor ramipril in hypertensive patients. J Int Med Res 33(Suppl 1):39A–49APubMedGoogle Scholar
  26. 26.
    Ariff B, Zambanini A, Vamadeva S, Barratt D, Xu Y, Sever P, Stanton A, Hughes A, Thom S (2006) Candesartan- and atenolol-based treatments induce different patterns of carotid artery and left ventricular remodeling in hypertension. Stroke 37:2381–2384CrossRefPubMedGoogle Scholar
  27. 27.
    Ichihara A, Kaneshiro Y, Takemitsu T, Sakoda M, Itoh H (2006) Benefits of candesartan on arterial and renal damage of non-diabetic hypertensive patients treated with calcium channel blockers. Am J Nephrol 26:462–468CrossRefPubMedGoogle Scholar
  28. 28.
    O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22CrossRefPubMedGoogle Scholar
  29. 29.
    Menard JR, Smith HE, Riebe D, Braun CM, Blissmer B, Patterson RB (2004) Long-term results of peripheral arterial disease rehabilitation. J Vasc Surg 39:1186–1192CrossRefPubMedGoogle Scholar
  30. 30.
    Ruger LJ, Irnich D, Abahji TN, Crispin A, Hoffmann U, Lang PM (2008) Characteristics of chronic ischemic pain in patients with peripheral arterial disease. Pain 139:201–208CrossRefPubMedGoogle Scholar
  31. 31.
    Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C (2008) Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 358:1547–1559CrossRefPubMedGoogle Scholar
  32. 32.
    Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC et al (1995) Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26:1235–1241CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • A. R. Zankl
    • 1
  • B. Ivandic
    • 1
  • M. Andrassy
    • 1
  • H. C. Volz
    • 1
  • U. Krumsdorf
    • 1
  • E. Blessing
    • 1
  • H. A. Katus
    • 1
  • C. P. Tiefenbacher
    • 1
  1. 1.Department of Cardiology and AngiologyUniversity of HeidelbergHeidelbergGermany

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