ABSTRACT: ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) trial demonstrated improved clinical outcome in patients undergoing percutaneous coronary intervention (PCI) pretreated with 600 vs. 300 mg clopidogrel loading dose. ARMYDA-2 SELECT is a prospectively planned subanalysis to investigate the effects of those different loading regimens on P-selectin levels.
From the ARMYDA-2 population, we investigated a subgroup of 84 patients (41 randomized to a 600 mg and 43 to a 300 mg clopidogrel loading dose given at a mean time of 6 h before PCI), in whom soluble P-selectin levels were measured at baseline (at the time of clopidogrel administration), immediately after the procedure, and after 8 and 24 h.
In the overall study population, a significant decrease of P-selectin levels was observed from baseline to intervention (from 91 ± 10 to 53 ± 15 ng/ml; P < 0.001). Baseline P-selectin levels were similar in the two groups, whereas at the time of intervention they were significantly lower in the high-dose arm (50 ± 13 vs. 58 ± 15 ng/ml; P = 0.048). P-selectin values between the two arms were not different at the subsequent determinations. The lowest procedural P-selectin levels were observed in patients of the 600 mg arm who had no postprocedural increase of troponin-I above normal limits (P ≤ 0.040).
Pretreatment with clopidogrel before PCI decreases peri-procedural P-selectin levels; moreover, a 600 mg clopidogrel loading dose, compared with the 300 mg regimen, is associated with reduction of peri-procedural myocardial damage and significant attenuation of P-selectin levels at the time of intervention. These results may help in identifying mechanisms underlying clinical benefit of the high clopidogrel load in PCI.
Journal of Cardiovascular Medicine 11/2010; 12(3):151-6. · 1.51 Impact Factor
ABSTRACT: The goal of this work was to investigate whether protection from myocardial injury during percutaneous coronary intervention (PCI) by atorvastatin is related to reduction of endothelial inflammatory response.
In the randomized ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) trial, 7-day pre-treatment with atorvastatin before PCI significantly reduced procedural myocardial injury; mechanisms underlying this effect are not characterized.
In a planned subanalysis of the ARMYDA trial, a subgroup of 76 patients was blind-tested for measurement of plasma levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and E-selectin: 38 patients belonged to atorvastatin (40 mg/day) and 38 to the placebo arm. Adhesion molecules were evaluated 7 days before intervention, immediately before PCI, and after 8 and 24 h.
Reduction of procedural myocardial injury after statin pre-treatment was also confirmed in this subgroup. Intercellular cell adhesion molecule-1, E-selectin, and VCAM-1 levels were not different at randomization and before intervention in either arm. At 8 h, increase of ICAM-1 levels was similar in the 2 arms, whereas 24-h levels were significantly lower in the atorvastatin versus placebo group (282 +/- 56 vs. 325 +/- 70 ng/ml; p = 0.007). Attenuation of E-selectin elevation occurred at 8 h in the atorvastatin group (50 +/- 8 vs. 59 +/- 13 ng/ml; p = 0.002) and became even more significant at 24 h (57 +/- 9 vs. 73 +/- 18 ng/ml; p = 0.0008). Vascular cell adhesion molecule-1 levels were not different at any time point in the 2 arms.
In patients undergoing PCI, reduction of procedural myocardial injury after 7-day pre-treatment with atorvastatin is paralleled by concomitant attenuation of post-procedural increase of ICAM-1 and E-selectin levels; thus, reduction of endothelial inflammatory response may explain this protective effect of statins.
Journal of the American College of Cardiology 11/2006; 48(8):1560-6. · 14.16 Impact Factor
ABSTRACT: Plasma concentrations of intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin may increase after percutaneous coronary intervention (PCI).
The aim of this study was to assess whether anti-inflammatory treatment with steroid-eluting stents influenced concentrations of adhesion molecules after PCI in patients with unstable coronary syndromes.
Consecutive patients with unstable coronary syndromes who were prospectively assigned to undergo implantation of a dexamethasone-eluting stent were compared with a control group of consecutive historical patients who received a similar non-drugeluting stent in the period immediately preceding availability of the steroid-eluting stents. Circulating concentrations of adhesion molecules were measured before the procedure and at 6 and 24 hours after implantation.
The study included 50 patients who received the dexamethasone-eluting stent (41 men, 9 women; mean [SD] age, 60  years) and 50 historical controls who received the non-drug-eluting stent (40 men, 10 women; mean age, 63  years). Baseline values for the adhesion molecules were similar in the 2 groups: in patients who received the dexamethasone-eluting stent, mean (SD) values were 210 (41) ng/mL for ICAM-1, 637 (119) ng/mL for VCAM-1, and 46 (9) ng/mL for E-selectin; in the control group, the corresponding values were 218 (42), 618 (140), and 43 (10) ng/mL. Circulating concentrations at 24 hours were significantly lower in patients receiving the drug-eluting stent compared with controls for both ICAM-1 (279  vs 338  ng/mL, respectively; P = 0.001) and VCAM-1 (772  vs 896  ng/mL; P = 0.004). There was no significant between-group difference in E-selectin concentrations at 24 hours (60  vs 56  ng/mL).
In this study, dexamethasone-eluting stents reduced plasma concentrations of ICAM-1 and VCAM-1 after PCI in patients with unstable coronary syndromes compared with historical controls.
Clinical Therapeutics 10/2005; 27(9):1411-9. · 2.32 Impact Factor
ABSTRACT: Endothelial dysfunction has been shown to be a critical early component of organ injury after myocardial ischemia and reperfusion. Circulating levels of adhesion molecules have been regarded as a valid index of endothelial activation. Recent reports suggest that statins, widely used in the control of hypercholesterolemia, exert a protective effect on the endothelium reflected by a reduced level of circulating adhesion molecules. In this study, the effects of preoperative simvastatin treatment, at doses equivalent to those used orally for cholesterol control, were studied on plasma levels of VCAM-1, ICAM-1, and ELAM-1.
A case-control study.
Fifteen patients taking simvastatin with good control of cholesterol levels, 15 patients not responsive to the simvastatin treatment, and 15 normocholesterolemic patients (control) undergoing elective coronary artery bypass surgery.
The plasma levels of VACM-1, ICAM-1, and ELAM-1 were evaluated at baseline; during cardiopulmonary bypass; and 6 hours, 24 hours, and 48 hours postoperatively. In the late postoperative samples, the plasma levels of ICAM-1 and ELAM-1 were lower in both simvastatin-treated patients compared with the control patients. No significant difference was found between the patients responsive to statin and those not responsive. Finally, no significant difference was found for VCAM-1 plasma levels between the control group and the 2 treatment groups.
Pretreatment with simvastatin significantly reduces the increase of ICAM-1 and ELAM-1 after coronary artery bypass surgery, by a mechanism that seems not related to its efficacy in lowering cholesterol levels.
Journal of Cardiothoracic and Vascular Anesthesia 11/2004; 18(5):605-9. · 1.64 Impact Factor