beraprost and Arteriosclerosis

Beraprost sodium (BPS, an analogue of prostacyclin) and telmisartan (TS, an angiotensin receptor blocker) have been reported to have a preventive effect on arterial stiffness in patients with cardiovascular diseases. The purpose of this study was to estimate the effects of a combined therapy using BPS and TS on arterial pulse wave velocity (PWV) values in elderly patients with hypertension and cerebral infarction. Over a 3-month period, 80 subjects with hypertension and histories of cerebral infarction received BPS only (120 microg/day p.o.), TS only (40 mg/day p.o.), both BPS and TS, or no medication at all (control). Arterial PWV and ankle brachial indices (ABI) were determined prior to and after 3 months of drug administration. During the follow-up, there were no significant changes in any of the parameters monitored with the exception of a significant decrease in systolic blood pressure in the BPS only, TS only, and BPS plus TS groups when compared to controls. The difference values for PWV in the control group, BPS only group, TS only group, and BPS plus TS group were +232.5, -114.6, -151.5, and -248.1 cm/s, respectively. The reduction values were significantly more pronounced in the BPS plus TS group than in the BPS only (P=0.037) and the TS only (P=0.022) groups. When BPS is combined with TS, an overall additive effect is seen in the improvement of PWV in Japanese patients with hypertension and cerebral infarction. This combination therapy is more beneficial than the corresponding monotherapies.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Arteriosclerosis; Benzimidazoles; Benzoates; Blood Flow Velocity; Cerebral Infarction; Double-Blind Method; Drug Therapy, Combination; Epoprostenol; Female; Humans; Hypertension; Male; Platelet Aggregation Inhibitors; Telmisartan; Treatment Outcome

The present study was conducted to examine the effects of acute administration of prostacyclin derivatives on plasma levels of adhesion molecules, endothelial function, and pulse wave velocity in patients with coronary heart disease.. In 20 patients with coronary heart disease, plasma levels of vascular cell adhesion molecule-1, P-selectin, and beta-thromboglobulin, endothelial function, and pulse wave velocity were assessed before and after the cold pressor test. These assessments were performed again 2 hr after the oral administration of prostacyclin derivatives (beraprost sodium 40 micrograms) or placebo. Endothelial function was assessed by changes in forearm blood flow before and after reactive hyperemia. Pulse wave velocity was determined by the volume rendering method.. Prostacyclin derivatives significantly improved endothelial function and decreased plasma beta-thromboglobulin level, but did not affect blood pressure and pulse wave velocity. Prostacyclin derivatives did not prevent the elevations of blood pressure and pulse wave velocity induced by the cold pressor test, but did prevent the elevations of P-selectin and beta-thromboglobulin induced by the cold pressor test.. Prostacyclin derivatives improved endothelial function and prevented platelet activation induced by the cold pressor test. Prostacyclin apparently has an anti-atherogenic effect.

Topics: Aged; Anti-Inflammatory Agents; Arteriosclerosis; beta-Thromboglobulin; Coronary Artery Disease; Endothelium, Vascular; Epoprostenol; Female; Humans; Male; Middle Aged; Pulse; Vascular Cell Adhesion Molecule-1

Prostacyclin (PGI(2)) inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. Arterial stiffness assessed by pulse wave velocity (PWV) predicts mortality in various cardiovascular diseases. To study the preventive effects of a prostacyclin analogue, beraprost sodium, on arterial PWV values in elderly patients with cerebral infarction. Forty-four patients with a history of cerebral infarction received beraprost sodium (120 microg/day p.o.) or no beraprost sodium (control) for 3 months. Arterial PWV and ankle brachial indices (ABI) were determined prior to starting the medication and after 3 months of medication. Initially, there were no differences in age, blood pressure, and body mass index. Further, PWV or ABI did not differ between the beraprost sodium group (n = 22) and the control group (n = 22). After 3 months, PWV in beraprost sodium group was significantly reduced (-123 +/- 282) when compared with the control group (147 +/- 274)(P = 0.006). ABI was not significantly different when comparing the two groups at 3 months. Long-term administration of beraprost sodium prevents the decline in arterial biomechanics in elderly patients with cerebral infarction.

Topics: Administration, Oral; Aged; Aged, 80 and over; Arteriosclerosis; Cerebral Infarction; Disease Progression; Double-Blind Method; Epoprostenol; Female; Humans; Male

We examined the effect of beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on restenosis after balloon angioplasty in the atherosclerotic artery in rabbits. Regional atherosclerosis was induced in the femoral artery of New Zealand white rabbits by balloon deendothelialization and 2% cholesterol diet. After establishment of atheroma in the femoral artery, angioplasty was performed. In all, 65 rabbits were assigned to the following six subcutaneous drug treatment groups: control group (n = 13, saline 0.25 ml/kg); BPS low-dose group (n = 11, BPS 50 micrograms/kg twice daily); BPS high-dose group (n = 12, BPS 100 micrograms/kg twice daily); 2-day BPS high-dose group (n = 11, BPS 100 micrograms/kg twice daily for 2 days after angioplasty); aspirin (ASA) group (n = 10, ASA 30 mg once daily); and BPS+ASA group (n = 8, BPS 50 micrograms/kg twice daily plus ASA 30 mg once daily). Administration of each drug was started 30 min before balloon angioplasty and was continued until 4 weeks thereafter, except in the 2-day BPS high-dose group. Re-examination 4 weeks after the angioplasty showed significant (p < 0.05) preservation of the luminal diameter in the BPS high-dose and 2-day BPS high-dose groups (1.30 +/- 0.15 and 1.25 +/- 0.09 mm, respectively) as compared with that in the control group (0.83 +/- 0.10 mm); however, the luminal diameter in the BPS low-dose, ASA, and BPS+ASA groups (0.94 +/- 0.18, 1.06 +/- 0.11, and 1.05 +/- 0.15 mm, respectively) was not significantly different from that in the control group.

Topics: Administration, Oral; Angioplasty, Balloon; Animals; Arteriosclerosis; Aspirin; Cholesterol, Dietary; Disease Models, Animal; Drug Synergism; Epoprostenol; Femoral Artery; Iliac Artery; Injections, Subcutaneous; Male; Platelet Aggregation Inhibitors; Rabbits; Random Allocation; Recurrence

Patients with carotid atheromatous lesions were prospectively studied with indium-111 platelet imaging, platelet aggregability and B-mode real-time ultrasound tests to determine the short-term effects of orally active prostacyclin analogue TRK-100 (40 micrograms, three times daily for 4 weeks). To establish baseline values, all patients underwent indium-111 platelet imaging, platelet aggregation study and B-mode ultrasound. The results were positive for carotid plaque and platelet accumulation. Visual analysis showed repeated platelet scintigrams to be unchanged in five patients without antithrombotic therapy; repeated ultrasound studies showed no change in eight of ten plaques, while one showed progression and one regression of the plaque. In five TRK-100 treated patients, five of seven lesions with platelet accumulation at the baseline became negative, and two remained unchanged during the treatment; repeated B-mode ultrasound tests indicated eight of nine plaques remained unchanged, while one showed plaque size reduction. Quantitative analysis demonstrated that, TRK-100 significantly reduced the ADP aggregation (1 microM) from 55.2 +/- 21.3% to 24.0 +/- 14.7% (+/- SD; p less than 0.05) and the platelet accumulation index (25.7 +/- 17.2% vs 10.4 +/- 10.4%; p less than 0.05). However, there was no significant reduction in plaque scores during TRK-100 therapy compared with the baseline (2.70 +/- 2.75 mm vs 2.51 +/- 2.58 mm). The data obtained suggested that short-term TRK-100 therapy has an inhibitory effect on platelet accumulation in carotid atheroma but does not cause significant changes in plaque size.

Topics: Administration, Oral; Aged; Arteriosclerosis; Blood Platelets; Carotid Artery Diseases; Epoprostenol; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Thrombosis