Sarpogrelate Hydrochloride

To assess the efficacy and safety of sarpogrelate (300 mg) for symptom improvement in patients having peripheral arterial disease (PAD) and/or being at risk of PAD in clinical practice using the Peripheral Artery Questionnaire (PAQ).

Symptomatic changes with antiplatelets in patients with PAD are limited.

To determine the effect and safety of sarpogrelate on the PAQ at 24 weeks from baseline.

A total of 1003 patients having PAD and/or being at risk of PAD from 17 tertiary hospitals in South Korea who were treated with sarpogrelate, were enrolled in this study. PAQs were collected at baseline and at 12 and 24 weeks, together with physical examination and vital signs measurements. Lifestyle pattern was also investigated.

The average PAQ Summary Score in the efficacy evaluation analysis group significantly improved from 62.9 ± 23.7 at baseline to 68.9 ± 21.7 at 24 weeks (P<0.0001). Physical limitation items significantly improved from 69.5 ± 30.0 at baseline to 72.9 ± 28.3 after 24 weeks (P=0.0011). Symptom stability also significantly improved from 52.1 ± 21.6 at baseline to 63.6 ± 22.9 after 24 weeks (P<0.0001). Symptoms, treatment satisfaction, quality of life, and social limitation domains all improved after treatment. A total of 201 patients reported adverse events (20.0%), not directly associated with treatment.

Treatment with 300 mg (orally) of sarpogrelate demonstrated statistically significant improvements in all domains and for the summary score of the PAQ at 24 weeks, it gave good results in terms of safety. Sarpogrelate may be helpful in reducing symptoms related to PAD.

Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT₂ receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT₂ blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT₂ antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT_1/5/7, 5-HT₇, 5-HT_1D and 5-HT_1F receptor agonists, respectively). Blocking 5-HT_1D/1F/7 receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT_1D/1F and 5-HT₇ activation.