Impact of timing from blood sampling to pharmacodynamic assessment on measures of platelet reactivity in patients treated with P2Y12 receptor inhibitors.

Several platelet function tests (PFT) are available to assess the pharmacodynamic (PD) effects of P2Y12 inhibitors. However, there are technical variances between PFT, and P2Y12 inhibitors differ in pharmacological properties. Manufactures of PFT recommend a time-frame within which assessments needs to be executed. However, if the timing from blood sampling to processing affects PD results is unknown. We conducted a prospective study assessing the impact of timing from blood sampling to processing on PD measures using three different PFT. We studied 60 aspirin-treated patients with coronary artery disease (CAD) on maintenance P2Y12 inhibiting therapy [clopidogrel 75 mg/day (n=20), prasugrel 10 mg/day (n=20) and ticagrelor 90 mg bid (n=20)]. PD assessments (trough levels) were performed by VerifyNow P2Y12 (VN), light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP) at 30 minutes, 2 and 4 hours post-sampling; VASP was also performed at 24 hours. P2Y12 reaction units (PRU) by VN significantly decreased over time with all P2Y12 inhibitors (clopidogrel p<0.001; prasugrel p=0.016; ticagrelor p<0.001). PRU at 30 minutes and 2 hours were similar, but decreased at 4 hours. LTA showed consistent findings with VN. Conversely, PD measures as assessed by VASP were stable over time (p>0.1 for all P2Y12 inhibitors). In conclusion, in CAD patients on maintenance therapy with P2Y12 inhibitors, timing from blood sampling to processing significantly influences PD measures as assessed by VN and LTA, but not by VASP.

[Assessment of dynamic coronary plaque changes and the clinical consequences in type-II diabetic patients: a serial intracoronary ultrasound study]. / Evaluación de los cambios dinámicos de las placas coronarias y sus consecuencias clínicas en pacientes con diabetes mellitus tipo 2: un estudio de ecografía intracoronaria seriada.

INTRODUCTION AND OBJECTIVES: One of the aims of secondary prevention is to achieve plaque stabilization. This study sought to investigate the clinical consequences and predictive factors of the change in the type of plaque (CTP) as assessed by serial intracoronary ultrasound in type II diabetic patients with known coronary artery disease. METHODS: 237 segments (45 patients) from the DIABETES I, II, and III trials were included. Intracoronary ultrasound from motorized pullbacks (0.5mm/s) after index procedure and at 9-month angiographic follow-up was performed in the same coronary segment. Nontreated mild lesions (angiographic stenosis <25%) with ≥0.5mm plaque thickening and ≥5mm of length assessed by intracoronary ultrasound were included. As different types of plaques may be encountered throughout a given coronary lesion, each study lesion was divided into 3 segments for serial quantitative and qualitative analyses. Statistical adjustment by multiple lesion segments per patient (generalized estimating equations method) was performed. A CTP was defined as any qualitative change in plaque type at follow-up. At 1-year follow-up, major adverse cardiac events - death, myocardial infarction and target vessel revascularization) - were recorded. RESULTS: A CTP was observed in 48 lesions (20.2%) and occurred more frequently (52.1%) in mixed plaques. Independent predictors of CTP were glycated hemoglobin levels (odds ratio [OR] 1.2; 95% confidence interval [CI] 1.01-1.5; P=.04); glycoprotein IIb-IIIa inhibitors (OR 0.3; 95% CI 0.1-0.7; P=.004) and statin administration (OR 0.3; 95% CI 0.1-0.8; P=.02). At 1-year follow-up CTP was associated with an increase in major adverse cardiac events rate (CTP 20.8% vs non-CTP 13.8%, P=.008; hazard ratio=1.9, 95% CI 1.3-1.9, P=.01). CONCLUSIONS: Qualitative changes in mild stenosis documented by intracoronary ultrasound in type II diabetics are associated with suboptimal secondary prevention and may have clinical consequences. Full English text available from: www.revespcardiol.org.

Assessment of potential relationship between wall shear stress and arterial wall response after bare metal stent and sirolimus-eluting stent implantation in patients with diabetes mellitus.

BACKGROUND: Wall shear stress (WSS) has been associated with neointimal hyperplasia (NIH) following bare metal stent (BMS) implantation. Drug-eluting stents (DES) almost abolish NIH. Conversely, diabetes mellitus amplifies NIH response. The association between WSS and arterial wall response following DES and BMS implantation in diabetic patients remains to be evaluated. METHODS: The study involved 20 diabetic patients randomized to BMS (n = 9) or sirolimus-eluting stent (SES; n = 11) implantation in native coronary arteries. A computational fluid dynamic model applied 3D intravascular ultrasound (IVUS) and two-plane angiographic to measure WSS (Pa). IVUS assessments were performed post-procedure and at 9-months follow-up. The target segment encompassed the stent plus 5 mm distal and proximal edges. A total of 93 subsegments were evaluated: in-stent segments divided in three subsegments (proximal, mid and distal; n = 60) and proximal and distal edges (n = 33). RESULTS: Stent length was similar between BMS (17.4 +/- 7.3 mm) and SES (19.8 +/- 6.8 mm) groups. NIH was observed in all BMS subsegments (n = 27) versus one subsegment in the SES group (n = 33). WSS ranged from 0.52 to 4.20 Pa in the BMS and from 0.42 to 3.06 Pa in the SES group. There was no correlation between WSS and NIH in either stent group. In addition, there were no correlation between the change of external elastic membrane (EEM) or plaque growth at the edges and WSS. CONCLUSION: WSS was not associated with NIH after implantation of SES or BMS in diabetic patients. Plaque growth or the change of EEM at the edges were not associated with WSS either.

Angiographic and 3D intravascular ultrasound assessment of overlapping bare metal stent and three different formulations of drug-eluting stents in patients with diabetes mellitus.

OBJECTIVES: The aim of this study was to examine the impact of overlapping bare-metal stent (BMS) and three different formulations of drug-eluting stent (DES) on intimal hyperplasia (IH) response of patients with diabetes mellitus (DM). METHODS: Forty-nine DM patients treated with overlapping BMS (19 lesions), sirolimus-eluting stent (SES 12 lesions), paclitaxel-eluting stent (PES 8 lesions) or tacrolimus-eluting stent (TES 10 lesions) were studied. Baseline and 9-month follow-up volumetric intravascular vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) analysis were performed in the entire stented segment and in the overlapped (OL) and non-overlapped (non-OL) subsegments. Clinical outcomes were evaluated at 1-year follow-up. RESULTS: Post-procedure (PO-) QCA measurements were similar in all stent groups, and between OL and non-OL subsegments in each individual type of stents. Percent IH was lower in SES and PES vs. BMS (p < 0.05). Percent IH was significantly greater in OL subsegment compared with non-OL subsegment in BMS (p < 0.05), but not in all type of DES groups. SES showed significantly less %IH compared with PES and TES in OL and non-OL subsegments. Vessel area at the OL remained unchanged from PO to FU in all type of DES and BMS groups. There were no aneurysm formation and no stent thrombosis up to 1-year follow-up. CONCLUSIONS: Overlapping BMS is associated with enhanced IH response in diabetic patients, whereas overlapping DES, particularly SES and PES, appear effective to inhibit IH without detectable late vascular adverse effects.