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Published in: Journal of Neurology 1/2013

Open Access 01-01-2013 | Original Communication

Effects of cilostazol against the progression of carotid IMT in symptomatic ischemic stroke patients

Authors: Sung Hyuk Heo, Ji Sung Lee, Beom Joon Kim, Kyoung Jin Hwang, Jun-Hyun Kim, Dae-Il Chang

Published in: Journal of Neurology | Issue 1/2013

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Abstract

Carotid intima-media thickness (IMT) is a surrogate marker for evaluating atherosclerotic vascular diseases. The phosphodiesterase inhibitor cilostazol attenuates the increase in carotid IMT in diabetes patients. We studied whether cilostazol can reduce the progression of carotid IMT in symptomatic ischemic stroke patients. From our prospective registry of acute ischemic stroke patients who were admitted during a 4.5-year period, follow-up carotid ultrasound was performed in a random sample of survivors. Patients were divided into two groups: the cilostazol group, who continued cilostazol treatment during the follow-up period; and the control group, who were prescribed antiplatelets other than cilostazol. Analysis of covariance and propensity score-matched analysis were used to evaluate the difference between groups. Among a total of 1,049 cases in our registry, 208 patients were utilized to construct two comparable sets by propensity score analysis, including 101 who received cilostazol and 107 who took antiplatelet medication without cilostazol. Both maximum and mean carotid IMT values were significantly reduced in the cilostazol group but increased in the control group (maximum left –0.048 ± 0.186 vs. 0.022 ± 0.163 mm, p = 0.001; maximum right –0.037 ± 0.173 vs. 0.050 ± 0.200 mm, p = 0.001; mean left –0.052 ± 0.102 vs. 0.023 ± 0.112 mm, p < 0.001; and mean right –0.038 ± 0.106 vs. 0.042 ± 0.139 mm, p < 0.001). After matching by propensity score, the improvements in both maximum and mean carotid IMT values in the cilostazol group remained significant. This study shows that cilostazol causes a significant regression in carotid IMT in symptomatic stroke patients.
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Literature
1.
go back to reference Ahn CM, Hong SJ, Park JH, Kim JS, Lim DS (2010) Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up. Heart Vessels 26:502–510PubMedCrossRef Ahn CM, Hong SJ, Park JH, Kim JS, Lim DS (2010) Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up. Heart Vessels 26:502–510PubMedCrossRef
2.
go back to reference Aizawa T, Wei H, Miano JM, Abe J, Berk BC, Yan C (2003) Role of phosphodiesterase 3 in NO/cGMP-mediated antiinflammatory effects in vascular smooth muscle cells. Circ Res 93:406–413PubMedCrossRef Aizawa T, Wei H, Miano JM, Abe J, Berk BC, Yan C (2003) Role of phosphodiesterase 3 in NO/cGMP-mediated antiinflammatory effects in vascular smooth muscle cells. Circ Res 93:406–413PubMedCrossRef
3.
go back to reference Amarenco P, Labreuche J, Lavallee P, Touboul PJ (2004) Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 35:2902–2909PubMedCrossRef Amarenco P, Labreuche J, Lavallee P, Touboul PJ (2004) Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 35:2902–2909PubMedCrossRef
4.
go back to reference Austin PC, Grootendorst P, Anderson GM (2007) A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study. Stat Med 26:734–753PubMedCrossRef Austin PC, Grootendorst P, Anderson GM (2007) A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study. Stat Med 26:734–753PubMedCrossRef
5.
go back to reference Cacoub PP, Abola MT, Baumgartner I, Bhatt DL, Creager MA, Liau CS, Goto S, Rother J, Steg PG, Hirsch AT (2009) Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the reduction of atherothrombosis for continued health (REACH) registry. Atherosclerosis 204:e86–e92PubMedCrossRef Cacoub PP, Abola MT, Baumgartner I, Bhatt DL, Creager MA, Liau CS, Goto S, Rother J, Steg PG, Hirsch AT (2009) Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the reduction of atherothrombosis for continued health (REACH) registry. Atherosclerosis 204:e86–e92PubMedCrossRef
6.
go back to reference Chambless LE, Folsom AR, Clegg LX, Sharrett AR, Shahar E, Nieto FJ, Rosamond WD, Evans G (2000) Carotid wall thickness is predictive of incident clinical stroke: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 151:478–487PubMedCrossRef Chambless LE, Folsom AR, Clegg LX, Sharrett AR, Shahar E, Nieto FJ, Rosamond WD, Evans G (2000) Carotid wall thickness is predictive of incident clinical stroke: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 151:478–487PubMedCrossRef
7.
go back to reference Dixon BS, Beck GJ, Vazquez MA, Greenberg A, Delmez JA, Allon M, Dember LM, Himmelfarb J, Gassman JJ, Greene T, Radeva MK, Davidson IJ, Ikizler TA, Braden GL, Fenves AZ, Kaufman JS, Cotton JR Jr, Martin KJ, McNeil JW, Rahman A, Lawson JH, Whiting JF, Hu B, Meyers CM, Kusek JW, Feldman HI (2009) Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med 360:2191–2201PubMedCrossRef Dixon BS, Beck GJ, Vazquez MA, Greenberg A, Delmez JA, Allon M, Dember LM, Himmelfarb J, Gassman JJ, Greene T, Radeva MK, Davidson IJ, Ikizler TA, Braden GL, Fenves AZ, Kaufman JS, Cotton JR Jr, Martin KJ, McNeil JW, Rahman A, Lawson JH, Whiting JF, Hu B, Meyers CM, Kusek JW, Feldman HI (2009) Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med 360:2191–2201PubMedCrossRef
8.
go back to reference Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Grines CL, Block E, Ghazzal ZM, Morris DC, Liberman H, Parker K, Jurkovitz C, Murrah N, Foster J, Hyde P, Mancini GB, Weintraub WS (2005) Coronary stent restenosis in patients treated with cilostazol. Circulation 112:2826–2832PubMedCrossRef Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Grines CL, Block E, Ghazzal ZM, Morris DC, Liberman H, Parker K, Jurkovitz C, Murrah N, Foster J, Hyde P, Mancini GB, Weintraub WS (2005) Coronary stent restenosis in patients treated with cilostazol. Circulation 112:2826–2832PubMedCrossRef
9.
go back to reference Dzau VJ, Braun-Dullaeus RC, Sedding DG (2002) Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med 8:1249–1256PubMedCrossRef Dzau VJ, Braun-Dullaeus RC, Sedding DG (2002) Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med 8:1249–1256PubMedCrossRef
10.
go back to reference Elam MB, Heckman J, Crouse JR, Hunninghake DB, Herd JA, Davidson M, Gordon IL, Bortey EB, Forbes WP (1998) Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscler Thromb Vasc Biol 18:1942–1947PubMedCrossRef Elam MB, Heckman J, Crouse JR, Hunninghake DB, Herd JA, Davidson M, Gordon IL, Bortey EB, Forbes WP (1998) Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscler Thromb Vasc Biol 18:1942–1947PubMedCrossRef
11.
go back to reference Feijge MA, Ansink K, Vanschoonbeek K, Heemskerk JW (2004) Control of platelet activation by cyclic AMP turnover and cyclic nucleotide phosphodiesterase type-3. Biochem Pharmacol 67:1559–1567PubMedCrossRef Feijge MA, Ansink K, Vanschoonbeek K, Heemskerk JW (2004) Control of platelet activation by cyclic AMP turnover and cyclic nucleotide phosphodiesterase type-3. Biochem Pharmacol 67:1559–1567PubMedCrossRef
12.
go back to reference Flu WJ, van Kuijk JP, Hoeks SE, Kuiper R, Schouten O, Goei D, Winkel T, van Gestel YR, Verhagen HJ, Bax JJ, Poldermans D (2009) Intima media thickness of the common carotid artery in vascular surgery patients: a predictor of postoperative cardiovascular events. Am Heart J 158:202–208PubMedCrossRef Flu WJ, van Kuijk JP, Hoeks SE, Kuiper R, Schouten O, Goei D, Winkel T, van Gestel YR, Verhagen HJ, Bax JJ, Poldermans D (2009) Intima media thickness of the common carotid artery in vascular surgery patients: a predictor of postoperative cardiovascular events. Am Heart J 158:202–208PubMedCrossRef
13.
go back to reference Hedblad B, Wikstrand J, Janzon L, Wedel H, Berglund G (2001) Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: main results from the beta-blocker cholesterol-lowering asymptomatic plaque study (BCAPS). Circulation 103:1721–1726PubMedCrossRef Hedblad B, Wikstrand J, Janzon L, Wedel H, Berglund G (2001) Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: main results from the beta-blocker cholesterol-lowering asymptomatic plaque study (BCAPS). Circulation 103:1721–1726PubMedCrossRef
14.
go back to reference Huang Y, Cheng Y, Wu J, Li Y, Xu E, Hong Z, Li Z, Zhang W, Ding M, Gao X, Fan D, Zeng J, Wong K, Lu C, Xiao J, Yao C (2008) Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. Lancet Neurol 7:494–499PubMedCrossRef Huang Y, Cheng Y, Wu J, Li Y, Xu E, Hong Z, Li Z, Zhang W, Ding M, Gao X, Fan D, Zeng J, Wong K, Lu C, Xiao J, Yao C (2008) Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. Lancet Neurol 7:494–499PubMedCrossRef
15.
go back to reference Kamal AK, Naqvi I, Husain, Khealani BA (2011) Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin. Cochrane Database Syst Rev 19:CD008076 Kamal AK, Naqvi I, Husain, Khealani BA (2011) Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin. Cochrane Database Syst Rev 19:CD008076
16.
go back to reference Katakami N, Kim YS, Kawamori R, Yamasaki Y (2010) The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type 2 diabetes mellitus: principal results of the diabetic atherosclerosis prevention by cilostazol (DAPC) study: a randomized trial. Circulation 121:2584–2591PubMedCrossRef Katakami N, Kim YS, Kawamori R, Yamasaki Y (2010) The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type 2 diabetes mellitus: principal results of the diabetic atherosclerosis prevention by cilostazol (DAPC) study: a randomized trial. Circulation 121:2584–2591PubMedCrossRef
17.
go back to reference Kodama M, Yamasaki Y, Sakamoto K, Yoshioka R, Matsuhisa M, Kajimoto Y, Kosugi K, Ueda N, Hori M (2000) Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Thromb Res 97:239–245PubMedCrossRef Kodama M, Yamasaki Y, Sakamoto K, Yoshioka R, Matsuhisa M, Kajimoto Y, Kosugi K, Ueda N, Hori M (2000) Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Thromb Res 97:239–245PubMedCrossRef
18.
go back to reference Kwon SU, Cho YJ, Koo JS, Bae HJ, Lee YS, Hong KS, Lee JH, Kim JS (2005) Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis. Stroke 36:782–786PubMedCrossRef Kwon SU, Cho YJ, Koo JS, Bae HJ, Lee YS, Hong KS, Lee JH, Kim JS (2005) Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis. Stroke 36:782–786PubMedCrossRef
19.
go back to reference Langenfeld MR, Forst T, Hohberg C, Kann P, Lubben G, Konrad T, Fullert SD, Sachara C, Pfutzner A (2005) Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 111:2525–2531PubMedCrossRef Langenfeld MR, Forst T, Hohberg C, Kann P, Lubben G, Konrad T, Fullert SD, Sachara C, Pfutzner A (2005) Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 111:2525–2531PubMedCrossRef
20.
go back to reference Lonn E, Yusuf S, Dzavik V, Doris C, Yi Q, Smith S, Moore-Cox A, Bosch J, Riley W, Teo K (2001) Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 103:919–925PubMedCrossRef Lonn E, Yusuf S, Dzavik V, Doris C, Yi Q, Smith S, Moore-Cox A, Bosch J, Riley W, Teo K (2001) Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 103:919–925PubMedCrossRef
21.
go back to reference Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115:459–467PubMedCrossRef Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115:459–467PubMedCrossRef
22.
go back to reference Lovett JK, Coull AJ, Rothwell PM (2004) Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology 62:569–573PubMedCrossRef Lovett JK, Coull AJ, Rothwell PM (2004) Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology 62:569–573PubMedCrossRef
23.
go back to reference Meijer R, Grobee DE, Bots ML (2006) Mannheim consensus on carotid intima-media thickness: opposite and complementary points of view. Cerebrovasc Dis 21:415–416PubMedCrossRef Meijer R, Grobee DE, Bots ML (2006) Mannheim consensus on carotid intima-media thickness: opposite and complementary points of view. Cerebrovasc Dis 21:415–416PubMedCrossRef
24.
go back to reference Mitsuhashi N, Tanaka Y, Kubo S, Ogawa S, Hayashi C, Uchino H, Shimizu T, Watada H, Kawasumi M, Onuma T, Kawamori R (2004) Effect of cilostazol, a phosphodiesterase inhibitor, on carotid IMT in Japanese type 2 diabetic patients. Endocr J 51:545–550PubMedCrossRef Mitsuhashi N, Tanaka Y, Kubo S, Ogawa S, Hayashi C, Uchino H, Shimizu T, Watada H, Kawasumi M, Onuma T, Kawamori R (2004) Effect of cilostazol, a phosphodiesterase inhibitor, on carotid IMT in Japanese type 2 diabetic patients. Endocr J 51:545–550PubMedCrossRef
25.
go back to reference Nakamura N, Hamazaki T, Johkaji H, Minami S, Yamazaki K, Satoh A, Sawazaki S, Urakaze M, Kobayashi M, Osawa H, Yamabe H, Okomura K (2003) Effects of cilostazol on serum lipid concentrations and plasma fatty acid composition in type 2 diabetic patients with peripheral vascular disease. Clin Exp Med 2:180–184PubMedCrossRef Nakamura N, Hamazaki T, Johkaji H, Minami S, Yamazaki K, Satoh A, Sawazaki S, Urakaze M, Kobayashi M, Osawa H, Yamabe H, Okomura K (2003) Effects of cilostazol on serum lipid concentrations and plasma fatty acid composition in type 2 diabetic patients with peripheral vascular disease. Clin Exp Med 2:180–184PubMedCrossRef
26.
go back to reference Riccioni G (2009) Statins and carotid intima-media thickness reduction: an up-to-date review. Curr Med Chem 16:1799–1805PubMedCrossRef Riccioni G (2009) Statins and carotid intima-media thickness reduction: an up-to-date review. Curr Med Chem 16:1799–1805PubMedCrossRef
27.
go back to reference Rosenbaum PR (1995) Observational studies. Springer, New York Rosenbaum PR (1995) Observational studies. Springer, New York
28.
go back to reference Shinoda-Tagawa T, Yamasaki Y, Yoshida S, Kajimoto Y, Tsujino T, Hakui N, Matsumoto M, Hori M (2002) A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with type II diabetes. Diabetologia 45:188–194PubMedCrossRef Shinoda-Tagawa T, Yamasaki Y, Yoshida S, Kajimoto Y, Tsujino T, Hakui N, Matsumoto M, Hori M (2002) A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with type II diabetes. Diabetologia 45:188–194PubMedCrossRef
29.
go back to reference Sidhu JS, Kaposzta Z, Markus HS, Kaski JC (2004) Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus. Arterioscler Thromb Vasc Biol 24:930–934PubMedCrossRef Sidhu JS, Kaposzta Z, Markus HS, Kaski JC (2004) Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus. Arterioscler Thromb Vasc Biol 24:930–934PubMedCrossRef
30.
go back to reference Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS (2008) Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 21:93–111 (quiz 189–190)PubMedCrossRef Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS (2008) Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 21:93–111 (quiz 189–190)PubMedCrossRef
31.
go back to reference Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, Weissman NJ, Turco M (2009) Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 361:2113–2122PubMedCrossRef Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, Weissman NJ, Turco M (2009) Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 361:2113–2122PubMedCrossRef
32.
go back to reference Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, Ebrahim S, Fatar M, Hernandez–Hernandez R, Kownator S, Prati P, Rundek T, Taylor A, Bornstein N, Csiba L, Vicaut E, Woo KS, Zannad F (2004) Mannheim intima-media thickness consensus. Cerebrovasc Dis 18:346–349PubMedCrossRef Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, Ebrahim S, Fatar M, Hernandez–Hernandez R, Kownator S, Prati P, Rundek T, Taylor A, Bornstein N, Csiba L, Vicaut E, Woo KS, Zannad F (2004) Mannheim intima-media thickness consensus. Cerebrovasc Dis 18:346–349PubMedCrossRef
33.
go back to reference Tsivgoulis G, Vemmos K, Papamichael C, Spengos K, Manios E, Stamatelopoulos K, Vassilopoulos D, Zakopoulos N (2006) Common carotid artery intima-media thickness and the risk of stroke recurrence. Stroke 37:1913–1916PubMedCrossRef Tsivgoulis G, Vemmos K, Papamichael C, Spengos K, Manios E, Stamatelopoulos K, Vassilopoulos D, Zakopoulos N (2006) Common carotid artery intima-media thickness and the risk of stroke recurrence. Stroke 37:1913–1916PubMedCrossRef
34.
go back to reference Yanase T, Nasu S, Mukuta Y, Shimizu Y, Nishihara T, Okabe T, Nomura M, Inoguchi T, Nawata H (2006) Evaluation of a new carotid intima-media thickness measurement by B-mode ultrasonography using an innovative measurement software, Intimascope. Am J Hypertens 19:1206–1212PubMedCrossRef Yanase T, Nasu S, Mukuta Y, Shimizu Y, Nishihara T, Okabe T, Nomura M, Inoguchi T, Nawata H (2006) Evaluation of a new carotid intima-media thickness measurement by B-mode ultrasonography using an innovative measurement software, Intimascope. Am J Hypertens 19:1206–1212PubMedCrossRef
Metadata
Title
Effects of cilostazol against the progression of carotid IMT in symptomatic ischemic stroke patients
Authors
Sung Hyuk Heo
Ji Sung Lee
Beom Joon Kim
Kyoung Jin Hwang
Jun-Hyun Kim
Dae-Il Chang
Publication date
01-01-2013
Publisher
Springer-Verlag
Published in
Journal of Neurology / Issue 1/2013
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-012-6599-y

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