A multicenter, randomized, open-labelled, non-inferiority trial of sustained-release sarpogrelate versus clopidogrel after femoropopliteal artery intervention. Optimal antiplatelet therapy after endovascular therapy (EVT) for peripheral artery disease is controversial. This trial aimed to evaluate whether sarpogrelate plus aspirin was non-inferior for preventing early restenosis after femoropopliteal (FP) EVT compared to clopidogrel plus aspirin. In this open-label, prospective randomized trial, 272 patients were enrolled after successful EVT for FP lesions. Patients in each group received aspirin 100 mg and clopidogrel 75 mg or sarpogrelate 300 mg orally once per day for 6 months. The primary outcome was target lesion restenosis at 6 months, tested for noninferiority. Patient
Effects of sarpogrelate on blood viscosity. The objective of the present study was to evaluate the effects and safety of sarpogrelate hydrochloride (sarpogrelate) in patients with elevated blood viscosity (BV), after 12 and 24 weeks of twice (BID) or thrice (TID) daily administrations of sarpogrelate (100 mg). The participants received oral sarpogrelate administration for 24 weeks and visited the hospital every 12 ± 2 week for blood viscosity measurements at shear rates of 5 and 300 s. The BV measured at shear rate of 5 s in male patients decreased significantly from 18.91 cP at the baseline to 16.3 cP after 24 weeks of sarpogrelate administration (13.6 % drop, p < 0.001). The BV measured at 5 s in female decreased more significantly from 17.5 cP at the baseline to 13.4 cP after 24 weeks
Effect of sarpogrelate and high-dose statin on the reduction of coronary spasm in vasospastic angina: A two by two factorial, pilot randomized study. Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high-dose statin have some effects on the reduction of coronary spasm in patients with VSA. We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high-dose statin (Group A, n = 25), sarpogrelate with low-dose or no statin (Group B, n = 25), placebo with high-dose statin (Group C, n = 25), and placebo with low-dose or no statin (Group D, n = 25). The primary endpoint
The Prevention of Contrast Induced Nephropathy by Sarpogrelate: a Prospective Randomized Controlled Clinical Trial. Although some strategies are used for prophylaxis of contrast induced nephropathy, their efficacy is not fully established. Sarpogrelate can relieve vasospasm and have anti-inflammatory action. This study examined whether sarpogrelate reduces the incidence of contrast induced nephropathy (CIN) or subsequent renal impairment during four weeks after coronary angiography compared with a control group. Seventy-four participants with chronic renal failure were randomly assigned to the sarpogrelate or control group. Patients assigned to the sarpogrelate group received oral saporogelate from 24 hours before contrast exposure up to one month after contrast exposure. The primary outcome
The Role of ERK1/2 Activation in Sarpogrelate-Mediated Neuroprotection. To characterize the mediators of 5-HT2A serotonin receptor-driven retinal neuroprotection. Albino mice were treated intraperitoneally with saline or sarpogrelate, a 5-HT2A antagonist, immediately before light exposure (LE). Following LE, retinas were harvested for a high-throughput phosphorylation microarray to quantify activated phosphorylated proteins in G protein-coupled receptor (GPCR) signaling. To confirm microarray results and define temporal changes, Western blots of select GPCR signaling proteins were performed. Since both methodologies implicated MAPK/ERK activation, the functional significance of sarpogrelate-mediated ERK1/2 activation was examined by inhibition of ERK1/2 phosphorylation via pretreatment
Effects of sarpogrelate, eicosapentaenoic acid and pitavastatin on arterioslcerosis obliterans-related biomarkers in patients with type 2 diabetes (SAREPITASO study) The aim was to evaluate the significance of arteriosclerosis obliterans-related biomarkers in patients with type 2 diabetes mellitus (T2DM), and to compare the effects of sarpogrelate, eicosapentaenoic acid (EPA) and pitavastatin on these markers. Seventy-two arteriosclerosis obliterans patients with T2DM were classified into two groups, pitavastatin with either sarpogrelate (PS) or EPA (PE). We observed no differences in all biomarkers between the PS and PE groups before treatments. The levels of body mass index, hemoglobin A1c, soluble E-selectin, soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1 and platelet
Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4-Way Replicate Crossover Investigation by a Reference-Scaled Average Bioequivalence Approach. Sarpogrelate is widely used to treat peripheral vascular disorders. However, it has been demonstrated to have a poor pharmacokinetic (PK) profile and marked within-subject variability. Here , the bioequivalence of 2 formulations of sarpogrelate (100-mg tablets) was assessed by using the reference-scaled average bioequivalence (RSABE) method, and the PK parameters were quantified in healthy Chinese subjects under fasting (n = 38) and fed (n = 35) conditions. In this open and randomized 4-way replicate study, a single dose of sarpogrelate was administered followed by a 3-day washout period
Sarpogrelate Based Triple Antiplatelet Therapy Improved Left Ventricular Systolic Function in Acute Myocardial Infarction: Retrospective Study The purpose of this study was to assess the potential benefit of a 5-hydroxytryptamine receptor antagonist, sarpogrelate-based triple antiplatelet therapy (TAPT) in comparison with dual antiplatelet therapy (DAPT) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). 119 patients of STEMI were retrospectively assessed. All patients received aspirin and clopidogrel per standard of care. Among them, 53 patients received an additional loading dose of sarpogrelate and a maintenance dose for 6 months post-PCI (TAPT group), while others did not (DAPT group). The rates of complete ST
Effect of sarpogrelate, a selective 5-HT Sarpogrelate, a 5-hydroxytryptamine type 2A antagonist, is a potential antiplatelet agent. We performed a randomized study to evaluate the effect of sarpogrelate on vascular health in Korean patients with diabetes. Forty diabetic patients aged 58.6 ± 6.8 years with 10-75% coronary artery stenosis, as assessed by coronary computed tomography angiography , were randomly assigned to sarpogrelate 300 mg/day plus aspirin 100 mg/day (SPG + ASA group) or aspirin 100 mg/day alone (ASA group) for 6 months. The primary endpoint of this study was the change in coronary artery disease including the calcium score (CACS), maximal stenosis, and plaque volume (calcified vs. noncalcified). The secondary endpoints were changes in biochemical parameters related
Multiple-Dose Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety in Healthy Subjects: A Comparison of Controlled-Release Sarpogrelate and Immediate-Release Sarpogrelate. To compare the pharmacokinetics, pharmacodynamics, and safety of sarpogrelate between controlled-release (CR) and immediate-release (IR) formulations after multiple-dose administration. This study was a randomized , open-label, 2-period, 2-treatment, crossover study in healthy subjects. All subjects received CR sarpogrelate 300 mg once daily and IR sarpogrelate 100 mg three times daily by random order each for 3 days with a 7-day washout period. Serial blood sampling was performed over 24 h. Pharmacokinetic parameters were determined by noncompartmental methods. Platelet aggregation to collagen, measured
Comparison of the Improvement and Safety of the Ankle Brachial Arterial Pressure Index of Sarpogrelate and Clopidogrel in Stroke Patients With Decreased Ankle Brachial Arterial Pressure Index and Intermittent Claudication of Lower Limb Vascular Atheroscl The clinical trial aims to confirm the improvement effect of the ankle brachial index and the safety of sarpogrelate administration compared to clopidogrel in stroke patients with decreased ankle brachial arterial pressure index and intermittent claudication of lower limb vascular atherosclerosis. Subjects are assigned to one of the two combinations through random allocation. Intervention group: Aspirin 100mg + sarpogrelate 300mg dosing group, Control group: Aspirin 100mg + clopidogrel 75mg dosing group. This clinical trial is a prospective open
Comparison of efficacy and safety of sarpogrelate-based anti-platelet therapy with clopidogrel-based anti-platelet therapy following arterial endovascular therapy: A systematic review PROSPERO International prospective register of systematic reviews Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith
Effectiveness of sarpogrelate after endovascular treatment for femoropopliteal artery disease: ESPALIER study. Optimal medical therapy following endovascular therapy (EVT) for femoropopliteal (FP) lesions remains unclear. Therefore, we investigated whether sarpogrelate improves primary patency after EVT for FP lesions. This study was performed as a multicenter, randomized, open-label clinical trial. 186 patients (mean age 75 ± 9 years, 78 % men) with Rutherford class 2-5 due to an FP lesion were randomly assigned to receive or not receive sarpogrelate in addition to aspirin. Primary endpoint was 1-year primary patency and the secondary endpoints were target lesion revascularization (TLR) and secondary patency. Primary patency was defined as a treated vessel without restenosis or repeat
Comprehensive Proteome Profiling of Platelet Identified a Protein Profile Predictive of Responses to An Antiplatelet Agent SarpogrelateSarpogrelate is an antiplatelet agent widely used to treat arterial occlusive diseases. Evaluation of platelet aggregation is essential to monitor therapeutic effects of sarpogrelate. Currently, no molecular signatures are available to evaluate platelet aggregation. Here, we performed comprehensive proteome profiling of platelets collected from 18 subjects before and after sarpogrelate administration using LC-MS/MS analysis coupled with extensive fractionation. Of 5423 proteins detected, we identified 499 proteins affected by sarpogrelate and found that they strongly represented cellular processes related to platelet activation and aggregation, including
Application of physiologically based pharmacokinetic modeling in predicting drug–drug interactions for sarpogrelate hydrochloride in humans Evaluating the potential risk of metabolic drug-drug interactions (DDIs) is clinically important. To develop a physiologically based pharmacokinetic (PBPK) model for sarpogrelate hydrochloride and its active metabolite, ()-1-{2-[2-(3-methoxyphenyl)ethyl ]-phenoxy}-3-(dimethylamino)-2-propanol (M-1), in order to predict DDIs between sarpogrelate and the clinically relevant cytochrome P450 (CYP) 2D6 substrates, metoprolol, desipramine, dextromethorphan, imipramine, and tolterodine. The PBPK model was developed, incorporating the physicochemical and pharmacokinetic properties of sarpogrelate hydrochloride, and M-1 based on the findings from in vitro
Beneficial Effects of Sarpogrelate and Rosuvastatin in High Fat Diet/Streptozotocin-Induced Nephropathy in Mice Chronic kidney disease (CKD) is a major complication of metabolic disorders such as diabetes mellitus, obesity, and hypertension. Comorbidity of these diseases is the factor exacerbating CKD progression. Statins are commonly used in patients with metabolic disorders to decrease the risk of cardiovascular complications. Sarpogrelate, a selective antagonist of 5-hydroxytryptamine (5-HT) 2A receptor, inhibits platelet aggregation and is used to improve peripheral circulation in diabetic patients. Here, we investigated the effects of sarpogrelate and rosuvastatin on CKD in mice that were subjected to a high fat diet (HFD) for 22 weeks and a single low dose of streptozotocin (STZ, 40 mg/kg). When
Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database Addition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion
Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly
Prospective Randomized Study of Sarpogrelate Versus Clopidogrel-based Dual Antiplatelet Therapies in Patients Undergoing Femoropopliteal Arterial Endovascular Interventions: Preliminary Results. Sarpogrelate is a selective 5-hydroxytryptamine (5-HT) receptor subtype 2A antagonist which blocks 5-HT induced platelet aggregation and proliferation of vascular smooth muscle cells. We compared the efficacy of sarpogrelate-based dual antiplatelet therapies for the prevention of restenosis and target lesion revascularization (TLR) rates comparing with that of clopidogrel after percutaneous endovascular interventions (EVIs) of femoropopliteal (FP) arterial lesions. This prospective, multicenter, randomized clinical trial recruited a total of 120 patients with successful EVI of FP lesions at seven
Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy. To determine if sarpogrelate, a selective 5-HT2A receptor antagonist, is protective against light-induced retinopathy in BALB/c mice. BALB/c mice were dosed intraperitoneally with 5, 15, 30, 40, or 50 mg/kg sarpogrelate 48, 24, and 0 hours prior to bright light exposure (10,000 lux) as well as 24 and 48 hours after exposure. Additionally, a single injection regimen was evaluated by injecting mice with 50 mg/kg sarpogrelate once immediately prior to light exposure. To investigate the potential for additive effects of serotonin receptor agents, a combination therapy consisting of sarpogrelate (15 mg/kg) and 8-OH-DPAT (1 mg/kg) was evaluated with the 5-day treatment regimen. Neuroprotection