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

The 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.

Hyper-Response to Clopidogrel in Japanese Patients Undergoing Transcatheter Aortic Valve Implantation.

Dual antiplatelet therapy is empirically recommended following transcatheter aortic valve implantation (TAVI). The aims of the present study were to analyze the effect of clopidogrel on platelet function and to determine the relative contribution of each CYP2C19 loss-of-function genotype undergoing TAVI.Thirty-two patients undergoing TAVI and with clopidogrel treatment were studied. All patients were treated with an Edwards SapienXT valve. Platelet reactivity was measured by the VerifyNow P2Y12 point-of-care assay at 7 days and 30 days after the procedure and a cutoff value of 95 PRU was used to identify a hyper-response of platelet reactivity. The Spartan RX(TM) sample-to-result point-of-care DNA testing system was used to identify CYP2C19 loss-of-function genotypes. Hyper-response of platelet reactivity was identified in 11 (34.3%) patients, although 24 (80%) were carriers of at least one CYP2C19 reduced-function allele. The PRU values did not change significantly from 7 days to 30 days after TAVI (136.7 ± 73.4 versus 150.4 ± 83.2, P = 0.13). The incidences of life-threatening bleeding, minor bleeding, and transfusion were significantly higher among the hyper-response of platelet reactivity group (27.3% versus 0%, P = 0.03, 36.4% versus 4.8%, P = 0.04, 81.8% versus 42.9%, P = 0.04, respectively).A hyper-response to clopidogrel was observed in one-third of patients undergoing TAVI and was related to bleeding events, even though 80% of the patients were carriers of the CYP2C19 reduced-function allele.

Effects of eicosapentaenoic acid on platelet function in patients taking long-term aspirin following coronary stent implantation.

Eicosapentaenoic acid (EPA) has been widely accepted to have antiatherosclerotic effects. The aim of this study was to investigate the antiplatelet effect of EPA combined with acetylsalicylic acid (ASA) following stent implantation. Eighteen patients who had undergone coronary stent implantation at least 8 months previously were included. All patients were given EPA ethyl ester (EPA-E) 1.8 g/day in addition to ASA 100 mg/day for 12 weeks. After the treatment, the plasma EPA/arachidonic acid (AA) ratio increased significantly from 0.40 ± 0.2 to 1.08 ± 0.39 (P < 0.001). There were no changes in the maximum platelet aggregation (MPA) induced by adenosine diphosphate (5 and 20 µmol/L), AA (0.3 and 0.5 mg/mL), or collagen (2 and 4 µg/mL). Furthermore, no significant differences were observed in the expression of PAC-1 and CD62P on the platelet surface membranes or in the soluble P-selectin concentration. With further analysis, a significant negative correlation was found between collagen (2 µg/mL)-induced MPA and plasma EPA/AA ratio (r = -0.507, P = 0.032). The patients were then divided into 2 groups according to the median EPA/AA ratio value of 0.92. In the high EPA/AA ratio group (n = 10), collagen-induced MPA was significantly suppressed after EPA-E administration (45.3 ± 15.9 versus 39.0 ± 16.3, P = 0.033). In contrast, there were no significant changes in platelet aggregation (56.0 ± 9.8 versus 57.1 ± 11.4, P = 0.745) in the low EPA/AA ratio group (n = 8). EPA treatment had a potential to suppress collagen-induced platelet aggregation in patients with a high plasma EPA/AA ratio.

Efficacy and safety of transcatheter aortic valve implantation with Edwards SAPIEN 3 and XT in smaller Asian anatomy.

We aimed to compare the efficacy and safety of transcatheter aortic valve implantation (TAVI) using Edwards SAPIEN 3 (S3) valve and SAPIEN XT) in smaller anatomy. The new generation S3 TAVI device has been used worldwide; however, its efficacy and safety in smaller Asian anatomy remain unknown. Between February 2014 and March 2017, 166 consecutive patients (S3, 54; XT, 112) were treated with balloon-expandable TAVI in a single center and their outcomes were analyzed. Median patient age was 85 (range: 81-88) years and mean body surface area was 1.41 ± 0.15 m2. A 23-mm size valve was used in S3 and XT groups (70 vs. 62%, p = 0.224). The transfemoral approach was more frequently used in the S3 than in the XT group (96 vs. 72%, p < 0.001). Although, the minimal luminal diameter of the femoral artery was smaller in the S3 group (5.9 vs. 6.4 mm, p = 0.001), the rates of major (2 vs. 11%, p = 0.226) and minor (11 vs. 5%, p = 0.107) vascular complications did not increase. The frequency of paravalvular leaks (PVL) ≥ 2 was significantly reduced in the S3 group (11 vs. 61%, p < 0.001); however, pre- (24 vs. 91%, p < 0.001) and post- (4 vs. 19%, p < 0.001) dilatations were less frequently performed. Pacemaker implantation incidence did not increase (4 vs. 5%, p = 1.0) and peak velocity of the transcatheter heart valve was significantly higher in the S3 group (2.3 vs. 2.2 m/s, p = 0.046). Device success was high (89 vs. 93%, p = 0.387) while the 30-day all-cause mortality was low (2 vs. 1%, p = 0.583) in both groups. TAVI with the S3 device was safe and effective, with low incidence of vascular complications and reduced PVL, in smaller body-sized Asians.

Predominant microvessel proliferation in coronary stent restenotic tissue in patients with diabetes: insights from optical coherence tomography image analysis.

BACKGROUND: Coronary optical coherence tomography (OCT) enables virtual depiction of histological findings of in-stent restenotic tissue. The aim of this study was to investigate the microvessel proliferation within in-stent restenotic tissue and the influence of diabetes mellitus (DM). METHODS: We examined 54 in-stent restenotic coronary artery lesions (stenotic area>50%) from 50 consecutive patients including 28 with DM (56%) and 9 insulin-treated DM patients (18%); who underwent coronary time-domain OCT imaging with automatic pull back (1mm/s, 20 frames/s). Microvessels were defined as low-signal cavities with a diameter of 50-150 microns and a trajectory parallel to the lumen recognized on 3 consecutive cross-sectional OCT image frames. The microvessel index was calculated as the number of frames with microvessel/total number of frames × 100. Patients were stratified into 3 groups: 1) without microvessels, 2) with a low (< median value) microvessel index, 3) with a high microvessel index. RESULTS: Microvessels were detected in 566 frames (3.1%) from 26 lesions (48%) in 24 patients (48%). A greater incidence of DM and higher serum glucose levels were observed in the high microvessel index group (DM: 42% vs 58% vs 83%, p=0.049; serum glucose level: 118.2 ± 44.6 vs 122.6 ± 31.0 vs 172.8 ± 63.1mg/dL, p=0.03 between low and high microvessel index group, p=0.005 between no microvessel and high microvessel index group). CONCLUSIONS: Microvessel formation may be a unique pathophysiological factor of in-stent restenoses in patients with DM.