Anti-atherosclerotic effect of sarpogrelate, a selective 5-HT2 antagonist, on arteriosclerosis obliterans (ASO) - On objective data, subjective symptoms, and overall improvement in a 30-month prospective study

Background: A selective 5-HT2 receptor antagonist, sarpogrelate, has been known to improve clinical symptoms in patients with arteriosclerosis obliterans (ASO). Many physicians have conducted in vitro studies to elucidate the mechanism involved in this effect and established that sarpogrelate inhibits platelet aggregation and proliferation of the vascular smooth muscle cells (VSMC). Methods: A total of 50 patients (30 older men and 20 postmenopausal women), all with a history of intermittent claudication and given a diagnosis of ASO, served as the subjects of this study. Sarpogrelate (200-300 mg/day) was prescribed for about 30 months. They were grouped by Fontaine classification (0-3). The intimal-medial thickness (IMT) of their carotid artery and cardiac function were measured and analyzed by ultrasonography and ultracardiosonography. The results of blood chemical analysis, blood pressure, and heart rate were analyzed at intervals of 3 or 6 months (starting at 0, then on the 3rd, 6th, 9th, 12th, 18th, 24th, and 30th month). Pulse wave velosity (PWV) was measured only for the last two years because no devices were available prior to that. The co-morbidity of these patients included: hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular disease, chronic renal failure, chronic glomerulonephritis, nephrotic syndrome, hyperlipidemia, and congestive heart failure. For these conditions, appropriate medication was prescribed in addition to sarpogrelate. Results: The IMT gradually decreased in most of the patients within the 30-month period (p < 0.0001). Sarpogrelate also improved PWV, ankle brachial pressure index (ABI), and cardiac functions (p < 0.0001) in spite of the complications cited above. The medication also enabled the patients with intermittent claudication to walk further distances and for a longer duration without pain in their lower extremities. This finding indicated that sarpogrelate exerts a direct effect to attenuate and inhibit both the progression and exacerbation of atherosclerosis (including arteriosclerosis). None of the patients experienced side effects from sarpogrelate during the trial. Conclusion: In the present study involving patients with ASO, sarpogrelate markedly improved the conditions of intermittent claudication, with increases in ABI and decreases in IMT and PWV, especially in those with diabetes mellitus.