© 1998 American Heart Association, Inc.
Original Contributions |
Effect of the Novel Antiplatelet Agent Cilostazol on Plasma Lipoproteins in Patients With Intermittent Claudication
From the Departments of Pharmacology and Medicine, University of Tennessee Health Science Center and Veterans Affairs Medical Center, Memphis, Tenn (M.B.E.); Otsuka America Pharmaceutical, Inc, Rockville, Md (J.H., E.B.B., W.P.F.); the Department of Medicine, Bowman Gray Medical Center, Winston-Salem, NC (J.R.C.); the University of California Irvine Medical Center, Orange, and Veterans Affairs Medical Center Long Beach, Long Beach, Calif (I.L.G.); the Heart Disease Prevention Clinic, University of Minnesota, Minneapolis (D.B.H.); Baylor Medical Center, Houston, Tex (J.A.H.); and the Chicago Center for Clinical Research, Chicago, Ill (M.D.).
Correspondence to Marshall B. Elam, PhD, MD, Division of Clinical Pharmacology, Departments of Pharmacology and Medicine, University of Tennessee Health Science Center, 874 Union Ave, Memphis, TN 38163. E-mail melam{at}utmem1.utmem.edu
Abstract—Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.
Key Words: HDL • intermittent claudication • triglycerides • cilostazol • apoA1
This article has been cited by other articles:
 |
|
 |
|
  M. E. O'Donnell, S. A. Badger, M. A. Sharif, R. R. Makar, I. S. Young, B. Lee, and C.V. Soong The Vascular and Biochemical Effects of Cilostazol in Diabetic Patients With Peripheral Arterial Disease Vascular and Endovascular Surgery, April 1, 2009; 43(2): 132 - 143. [Abstract] [PDF]
|
|
|
|
 |
|
 R. M. de Albuquerque, C. E. Virgini-Magalhaes, F. Lencastre Sicuro, D. A. Bottino, and E. Bouskela Effects of Cilostazol and Pentoxifylline on Forearm Reactive Hyperemia Response, Lipid Profile, Oxidative Stress, and Inflammatory Markers in Patients With Intermittent Claudication Angiology, October 1, 2008; 59(5): 549 - 558. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Sobel and R. Verhaeghe Antithrombotic Therapy for Peripheral Artery Occlusive Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 815S - 843S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hiratsuka, Y. Hinai, T. Sasaki, Y. Konno, K. Imagawa, M. Ishikawa, and M. Mizugaki Characterization of Human Cytochrome P450 Enzymes Involved in the Metabolism of Cilostazol Drug Metab. Dispos., October 1, 2007; 35(10): 1730 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Casey, B. H. Tonnessen, W. C. Sternbergh III, and S. R. Money Medical Management of Intermittent Claudication Vascular and Endovascular Surgery, September 1, 2004; 38(5): 391 - 399. [Abstract] [PDF]
|
|
|
|
 |
|
 S. M Dean Pharmacologic treatment for intermittent claudication Vascular Medicine, November 1, 2002; 7(4): 301 - 309. [Abstract] [PDF]
|
|
|
|
|
|
D. L. Dawson, Qintian Zheng, S. A. Worthy, B. Charles, and D. V. Bradley Failure of Pentoxifylline or Cilostazol to Improve Blood and Plasma Viscosity, Fibrinogen, and Erythrocyte Deformability in Claudication Angiology, September 1, 2002; 53(5): 509 - 520. [Abstract] [PDF]
|
|
|
|
 |
|
 J. A. Beckman, M. A. Creager, and P. Libby Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management JAMA, May 15, 2002; 287(19): 2570 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Strandness Jr, R. L. Dalman, S. Panian, M. S. Rendell, P. C. Comp, P. Zhang, and W. P. Forbes Effect of Cilostazol in Patients with Intermittent Claudication: A Randomized, Double-Blind, Placebo-Controlled Study Vascular and Endovascular Surgery, March 1, 2002; 36(2): 83 - 91. [Abstract] [PDF]
|
|
|
|
|
|
E. R Mohler III, H. G Beebe, S. Salles-Cuhna, R. Zimet, P. Zhang, J. Heckman, and W. P Forbes Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication Vascular Medicine, August 1, 2001; 6(3): 151 - 156. [Abstract] [PDF]
|
|
|
|
 |
|
 I. L. Gordon, R. M. Conroy, M. Arefi, J. M. Tobis, E. A. Stemmer, and S. E. Wilson Three-Year Outcome of Endovascular Treatment of Superficial Femoral Artery Occlusion Arch Surg, February 1, 2001; 136(2): 221 - 228. [Abstract] [Full Text] [PDF]
|
|