Volume 3, Number 5: MAY 2000

Comparison of the Effects of Acetylsalicylic Acid, Ticlopidine and Cilostazol on Primary Hemostasis Using a Quantitative Bleeding Time Test Apparatus

Effect of cilostazol on cerebral blood flows in chronic stage of cerebral circulation. 

Long-term results following operation for diabetic foot problems: arterial disease confers a poor prognosis. 

Increased platelet aggregability in response to shear stress in acute myocardial infarction and its inhibition by combined therapy with aspirin and cilostazol after coronary intervention. 

 

Comparison of the Effects of Acetylsalicylic Acid, Ticlopidine and Cilostazol on Primary Hemostasis Using a Quantitative Bleeding Time Test Apparatus. 

Reference: Haemostasis 2000;29(5):269-276.

We examined and compared the effects of aspirin (ASA), ticlopidine (TP) and cilostazol (CS) on bleeding time (BT) in 10 healthy adult male subjects using a newly developed quantitative bleeding time (QBT) test apparatus capable of simultaneously measuring total blood loss (Tv), maximum bleeding rate (Rmax), and bleeding pattern in addition to BT. All 3 drugs inhibited platelet aggregation response to ADP, collagen, epinephrine and arachidonic acid (p < 0.05), but not to ristocetin. Following oral administration of ASA (330 mg/day) or TP (300 mg/day) for 3 days, BT was significantly prolonged (mean BT increased from 359.3 to 646.0 s, p < 0.001, and from 323.3 to 528.7 s, p < 0.01, respectively) and Tv was significantly increased (from 14.5 to 30.2 mul, p < 0.05, and from 12.5 to 19.2 mul, p < 0.01, respectively). Aspirin also increased Rmax (from 0.118 to 0.159 mul/s, p < 0.05). The prolonged bleeding patterns after administration of ASA and TP were both type III, which has been reported to be less likely to lead to bleeding accidents. In contrast, none of these QBT parameters were altered by CS administration.

Effect of cilostazol on cerebral blood flows in chronic stage of cerebral circulation. 

Reference: Keio J Med 2000;49S1:A146-7.

In order to find out the difference between cilostazol and ticlopidine hydrochloride in the cerebral vasodilating effect in the chronic stage of cerebral infarction, cerebral blood flows were measured while the patients were on ticlopidine hydrochloride and after ticlopidine hydrochloride was switched to cilostazol. Single photon emission computed tomography (SPECT) was performed using Prism 2000XP gamma camera system. Ultrasound examinations of the carotid artery was performed using Ultramark 9. The blood flows in the frontal white matter, temporal cortex and occipital cortex after cilostazol were significantly higher than those before cilostazol. The peak systolic velocity, time-averaged peak velocity and volume flow after cilostazol were significantly higher than those before cilostazol. The total cholesterol, triglyceride and apolipoprotein B concentrations after cilostazol were significantly lower than those before cilostazol. The present study suggests that cilostazol has better influence on cerebral circulation.

Long-term results following operation for diabetic foot problems: arterial disease confers a poor prognosis. 

Reference: Eur J Vasc Endovasc Surg 2000;19(2):174-7

OBJECTIVES: to describe the long-term outcome of local amputations and debridements of diabetic feet, with special reference to the presence or absence of arterial disease. 

MATERIALS AND METHODS: a consecutive series of 75 diabetic patients having local foot surgery during 1987-92 was
reviewed in 1998. A total of 136 operations had been done on 92 limbs, of which 52 (60%) had evidence of arterial disease. Survivors were interrogated in 1998, with follow-up intervals of 69-120 (median 92) months after their index operations. 

RESULTS: complete healing occurred in 48% feet, and 36% limbs required major amputation, after 1 day-7 years (median 24 days). Major amputation was more common in limbs with arterial disease (52% vs. 18%) -p;<0.001. At follow-up 20 (27%)
patients were alive (five lost to long-term follow-up) - five of 44 (11%) arteriopaths, and 15 of 26 (58%) of those without arterial disease (p<0.001). No patient who had arterial reconstruction at the outset survived to follow-up. Among the survivors, 78% feet had remained healed, with no recurrent ulceration. 

CONCLUSIONS: among diabetics requiring local foot surgery, the presence of arterial disease confers a poor long-term prognosis for both life and limb. Those with neuropathy alone tend to do well with good foot care.

Although antiplatelet therapy with a specific inhibitor of phosphodiesterase-3 cilostazol improves stent patency compared with use of aspirin (ASA) alone, the specific role of cilostazol on platelet aggregation in patients with acute myocardial infarction (AMI) is less well understood. Thirty-six patients with AMI who were successfully treated with primary angioplasty were randomized to 3 antiplatelet regimens: ASA alone (n = 12), ASA + ticlopidine (n = 12), and ASA + cilostazol (n = 12).
We measured shear stress-induced platelet aggregation (SIPA) using a modified cone-plate viscometer on admission and on day 7, and evaluated the inhibitory effects of combination therapy with ASA + cilostazol on SIPA. Compared with cases of stable coronary artery disease, significant increases in SIPA and plasma von Willebrand factor activity were observed in patients with AMI before they received antiplatelet therapy. On day 7 after primary angioplasty, ASA did not inhibit SIPA (65 +/- 15% vs 57 +/- 11%, p = 0.086), whereas both combination therapies of ASA + ticlopidine and ASA + cilostazol significantly inhibited SIPA in patients with AMI (ASA + ticlopidine: 61 +/- 15% vs 45 +/- 13%, p <0.0001; ASA + cilostazol: 64 +/- 14% vs 43 +/- 9%, p <0.005). There was a significant correlation of SIPA with adenosince diphosphate (ADP)-induced platelet aggregation
(r = 0.412, p = 0.003) and with plasma von Willebrand factor activity (r = 0.461, p = 0.0008). These data suggest that patients with AMI have increased platelet aggregability in response to high shear stress. Combined antiplatelet therapy with ASA + cilostazol appears to be as effective as therapy with ASA + ticlopidine for reducing SIPA in patients with AMI who are undergoing primary angioplasty.