Add-on Antiplatelet Effects of Eicosapentaenoic Acid With Tailored Dose Setting in Patients on Dual Antiplatelet Therapy

Abstract

SummaryThe aim of this study was to investigate the antiplatelet effects of eicosapentaenoic acid (EPA) at a sufficient dose following coronary stent implantation. Thirty-one patients on dual antiplatelet therapy with aspirin and clopidogrel were treated with highly purified EPA-E (Epadel ® ) for 12 weeks. Based on our previous study, patients with a high baseline EPA/arachidonic acid (AA) ratio (≥ 0.37; n = 11) were given a standard dose (1800 mg daily) of EPA-E, whereas those with a low EPA/AA ratio (< 0.37; n = 20) were given a high dose (2700 mg daily) to reach the target value of > 0.92. Platelet function was then evaluated with agonist-induced aggregation using light transmittance aggregometry and VerifyNow ® . After EPA-E treatment, the EPA/AA ratio significantly increased from 0.28 to 1.31 (P < 0.001). Collagen (1, 2, and 4 μg/mL)-induced maximal platelet aggregation (MPA) was significantly suppressed after EPA-E administration (from 28.0 to 24.0, P = 0.033; from 44.0 to 40.0, P = 0.016; from 60.0 to 56.0, P = 0.010; respectively). However, there were no changes in MPA induced by adenosine diphosphate and AA and in P2Y12 reaction units (PRU) and aspirin reaction units. After EPA-E treatment, PRU was significantly suppressed in 8 patients showing high on-treatment platelet reactivity (HTPR) (baseline 305; 266-321 versus on-treatment 256; 233-261, P = 0.012), but not in those without HTPR (201; 156-220 versus 183; 159-233, P = 0.212). In conclusion, EPA treatment at a sufficient dose suppressed platelet aggregation and showed possible add-on effects in patients with clopidogrel hyporesponsiveness. (Int Heart J 2017; 58: 481-485) Key words: EPA/AA ratio, Clopidogrel, Platelet function, Coronary artery disease E icosapentaenoic acid (EPA) is believed to inhibit platelet function. 1-3) However, except for animal experiments, the antiplatelet effect of EPA has not yet been clinically established, especially in patients with coronary stent implantation who are on dual antiplatelet therapy with acetyl salicylic acid (ASA) and clopidogrel. We have studied the effects of highly purified EPA (EPA-E; Epadel ® 1,800 mg daily for 4 weeks) on adenosine diphosphate (ADP)-, collagen-, and arachidonic acid (AA)-induced platelet aggregation in patients following coronary stent implantation, and the results were insignificant. 4) However, in that particular study, the on-treatment plasma EPA level or the EPA/AA ratio were negatively correlated with collagen-induced maximum platelet aggregation (MPA), and platelet function was significantly suppressed in subjects whose EPA/AA ratios were over the median cut-off value of 0.92. Accordingly, it is important to know whether administering a sufficient dose of EPA-E in a tailor-made manner could raise the EPA/AA ratio to > 0.92 in every patient and whether platelet function could be effectively suppressed using this strategy.As for antiplatelet therapy following coronary stent implantation in the era of the drug-eluting stent (DES), the effectiveness and safety of dual antiplatele...

Omega-3 Polyunsaturated Fatty Acids and Stroke Burden

“…On the other hand, 1800 mg of EPA showed a significant reduction in stroke incidence in the JELIS study in the secondary stroke prevention subgroup, and moreover, 4 g of EPA reduced stroke incidence in the REDUCE-IT study [52,54]. There is evidence that EPA at a sufficient dose (1800 or 2700 mg/d) suppressed the platelet aggregation function in patients on antiplatelet therapy [55]. Therefore, high doses of n-3 PUFAs, especially EPA, might have a stroke prevention effect.…”

Outcomes in Patients with Critical Limb Ischemia due to Arteriosclerosis Obliterans Who Did Not Undergo Arterial Reconstruction

“…DAPT carries a risk of bleeding diseases such as gastrointestinal tract and intracranial bleeding. 24,25) In our study, DAPT was administered in 25% of all patients and in 50% of patients who lived for longer than two years. The management of other medical conditions is important prior to surgery and prior to other treatments for CLI.…”

Initial Report of the Perioperative Platelet Aggregation Test Using Hematracer ZEN in Neuroendovascular Therapy

“…In this method, after a platelet-aggregation-inducing substance (ADP, collagen) is added to whole blood, aspiration through a micromesh filter (diameter: 30 mm) is performed to measure the aspiration pressure associated with blood-clot-related clogging. The PATI, as a minimum concentration of a plateletaggregation-inducing substance required to obtain secondary As factors that influence the responsiveness to CLP on a platelet aggregation test using the VerifyNow system, combination therapy with EPA preparations, which may reduce the PRU value, 18) and statin preparations, which may increase the PRU value, 19,20) were reported. In this study, there were no significant differences in the rate of patients who received EPA or statin preparations between the excessive CLP efficacy and optimal groups on preoperative assessment.…”