Failure of pentoxifylline or cilostazol to improve blood and plasma viscosity, fibrinogen, and erythrocyte deformability in claudication.
Cilostazol, a potent phosphodiesterase type III inhibitor, selectively increases antiatherogenic high-density lipoprotein subclass LpA-I and improves postprandial lipemia in patients with type 2 diabetes mellitus.
State of treatment of coronary artery disease by drug releasing stents
The intermittent claudication questionnaire: A patient-assessed condition-specific health outcome measure.

Failure of pentoxifylline or cilostazol to improve blood and plasma viscosity, fibrinogen, and erythrocyte deformability in claudication. Reference: Angiology 2002 Sep-Oct;53(5):509-20 Peripheral artery disease is associated with altered blood rheologic properties, including increased viscosity and decreased red blood cell (RBC) deformability. Pentoxifylline and cilostazol are available therapies for intermittent claudication. Improvement of blood viscosity and erythrocyte deformability have been cited as potential mechanisms of action for pentoxifylline. Cilostazol is a new drug with antiplatelet and vasodilating activity, but the mechanism by which it promotes an improvement in walking is not known. This study was performed to evaluate and compare the hemorheologic effects of pentoxifylline and cilostazol on viscosity, fibrinogen levels, and erythrocyte deformability when administered to adults with moderate to severe claudication. A double-blind, controlled study was conducted and included 59 patients (46 male, 13 female; mean age 65 yr) randomized to pentoxifylline 400 mg orally thrice daily (n=20), cilostazol 100 mg orally twice daily (n=19), or placebo (n=20); all subjects were observed for 24 weeks. Walking ability was assessed before, during, and at the conclusion of treatment by standard constant speed, variable grade treadmill testing. Erythrocyte deformability was measured by passage of washed RBCs, 10% hematocrit in phosphate buffered saline (PBS), through a polycarbonate membrane with 4.7 to 5.0 microm pores. Whole blood and plasma viscosity were measured using a cone/plate viscometer at variable shear rates (from 4.5 to 450 sec(-1)). Erythrocyte sedimentation rate was measured by a modified Westergren technique. Fibrinogen was assayed by a commercial reference laboratory. Plasma viscosities did not change significantly in any treatment group. Within-group comparisons demonstrated a significant (p<0.01) drop in whole blood viscosity (week 24 compared with week 0) for cilostazol-treated subjects (at shear rates of 45, 90, 225, and 450 sec(-1)), but these changes were not significantly different from those in the placebo group. There were no significant changes in whole blood viscosity for subjects treated with pentoxifylline or placebo. There were no significant changes in erythrocyte deformability, fibrinogen, or erythrocyte sedimentation rate. A trend toward improved walking distances was noted for both pentoxifylline and cilostazol in comparison with placebo. This trend was not correlated with changes in any underlying rheologic parameter. Ex vivo rheologic characteristics of blood from patients with intermittent claudication are not significantly affected by long-term administration of pentoxifylline or cilostazol. Pentoxifylline did not modulate viscosity or red cell deformability, a finding at variance with its putative mechanism of action. Pentoxifylline cannot be differentiated from cilostazol based on specific hemorheologic effects evaluated in this study. Different mechanisms of action for these medications should be considered. Cilostazol, a potent phosphodiesterase type III inhibitor, selectively increases antiatherogenic high-density lipoprotein subclass LpA-I and improves postprandial lipemia in patients with type 2 diabetes mellitus. Reference: Metabolism 2002 Oct;51(10):1348-54 Low levels of high-density lipoproteins cholesterol (HDL-C) as well as impaired postprandial lipemia are known to be associated with the increased risk for coronary artery disease (CAD) in patients with type 2 diabetes mellitus (type 2 DM). HDL are heterogeneous in size and apolipoprotein composition. Recent evidence indicates that among the 2 major HDL subclasses, those without apolipoprotein A-II (LpA-I) are more antiatherogenic compared with those with apoA-II (LpA-I:A-II). Cilostazol, a novel selective phosphodiesterase type III inhibitor, has been shown to inhibit platelet activation and is also a potent vasodilator. Additionally, cilostazol has been shown to modulate lipoprotein profiles by raising HDL-C and lowering plasma triglyceride (TG) levels. The present study investigated the effect of cilostazol on HDL composition (LpA-I and LpA-I:A-II levels) and postprandial lipemia in patients with type 2 DM. Seventeen patients were given cilostazol 200 mg twice daily for 12 weeks. At weeks 0 and 12, fat tolerance tests (30 g/m(2)) were performed to assess postprandial lipemia. Plasma TG and remnant-like lipoprotein particles cholesterol (RLP-C) were significantly decreased by 17% and 26%, respectively (P <.05), and HDL-C was significantly increased by 14% (P <.01). LpA-I was significantly increased by 23% (P <.01) from the mean value of 45 mg/dL to 55 mg/dL. In contrast, LpA-I:A-II remained unchanged, resulting in significantly increased %LpA-I (apoA-I on LpA-I/total apoA-I x 100) from 35% to 40% (P <.01). Areas under the curve for TG and RLP-C after the fat meal were both nonsignificantly decreased by 17%. Patients with higher plasma TG levels had a greater benefit from the treatment with cilostazol as revealed by fasting TG levels and fat tolerance tests. HDL-C responses to cilostazol were independent of baseline plasma TG levels or percentage changes in TG, indicating that the underlying mechanisms for raising HDL and reducing TG levels are distinct. In conclusion, cilostazol selectively increased LpA-I, thus favorably altering HDL towards a more antiatherogenic composition. This finding, together with the improved postprandial lipemia, indicates that cilostazol has a potent antiatherogenic function by modulating HDL and remnant metabolism in patients with type 2 DM.                              State of treatment of coronary artery disease by drug releasing stents Reference: Herz 2002 Sep;27(6):508-13 BACKGROUND: Despite improved technologies restenosis remains the main drawback of catheter-based interventions in coronary artery disease. Local application of anti-proliferative drugs through drug releasing stents is a promising concept addressed to solve this problem.  DRUG RELEASING STENTS: Today, given the technical capabilities for controlled drug release from coronary stents, the development of drug eluting stents has emerged as one of the main research areas in interventional cardiovascular medicine. Several different approaches for drug loading on coronary stents as well as a variety of antiproliferative and anti-inflammatory agents, such as paclitaxel, actinomycin D, sirolimus, tacrolimus, everolimus and dexamethasone are under clinical investigation.  RESULTS: Since the first enthusiastic reports from first in-man observations with drug coated stents, the success of the combination of both a biological and a mechanical approach has been proved in several controlled studies with restenosis rates between 0% in the RAVEL trial (sirolimus, Cordis Bx Velocity trade mark stent), 0% in the TAXUS I trial (paclitaxel, Boston Scientific NIRx trade mark stent) and 4% in the ASPECT Study (paclitaxel, Cook V-Flex plus trade mark stent). The risk of stent thrombosis seems to depend on the dose of the antiproliferative drug - in the SCORE trial stent thrombosis occurred in 6.3% of patients with high dose of QP2 and the antiplatelet therapy, in the ASPECT subgroup with cilostazol instead of clopidogrel and high dose of paclitaxel in up to 25%, whereas in RAVEL and TAXUS I no stent thrombosis was observed. CONCLUSION: If the "one digit" restenosis rate observed in clinical trials could be confirmed in clinical practice without increase of complications, especially stent thrombosis using multiple and/or long stents, we can expect in the near future that implanting drug eluting stents in larger patient groups and lesion subsets will cause a reduction of patients with need for surgical revascularization.           The intermittent claudication questionnaire: A patient-assessed condition-specific health outcome measure. Reference: J Vasc Surg 2002 Oct;36(4):764-71 INTRODUCTION: As yet, there is no patient-assessed, condition-specific instrument for the assessment of health-related quality of life in intermittent claudication. We evaluated the intermittent claudication questionnaire (ICQ) for properties required of a measure of health outcome.  METHODS and RESULTS: Interviews with patients with intermittent claudication and vascular specialist opinion produced a pool of statements used to itemize a self-completed ICQ. This was piloted in 20 patients for practicality and then administered to 124 stable claudicants. Reliability was assessed through a retest in 63 (51%) patients at 14 days and analysis of Cronbach's alpha for internal consistency. Spearman's correlation coefficient was used to assess construct validity in comparisons between the ICQ and ankle brachial pressure index, treadmill-walking distances, the walking impairment questionnaire, the EuroQol, and the Short Form-36. Responsiveness of the ICQ to changes in health was assessed in 60 patients treated conservatively and 40 patients undergoing angioplasty. The standardized response mean was used to identify the most responsive instrument in the study. A 16-item ICQ with a test-retest intraclass correlation of 0.95 and Cronbach's alpha of.94 was produced. One hundred twenty-one (98%) patients completed the ICQ (mean time, 3.7 minutes). The ICQ correlated better with the EuroQol (r = 0.58) and 7 out of 8 subscales of the Short Form-36 (r = 0.33-0.68) compared with the walking impairment questionnaire. The ICQ demonstrated the largest standardized response mean in relation to health transition compared with the other instruments.  CONCLUSIONS: The patient-assessed ICQ is a practical, reliable, valid, and responsive measure of patient health-related quality of life in intermittent claudication.