Resistance to thienopyridines: Clinical detection of coronary stent thrombosis by monitoring of vasodilator‐stimulated phosphoprotein phosphorylation

Abstract

We carried out a prospective evaluation of a new vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay in order to detect patients with high-risk coronary subacute stent thrombosis (SAT) despite thienopyridine regimen. Twenty healthy donors (group 1) without any medication were compared to 16 stented patients (group 2) treated by ticlopidin or clopidogrel initiated 2 days before stenting and aspirin (250 mg/day). No difference in platelet reactivity was noted between group 1 and group 2 treated only with aspirin (72.00% +/- 4.17% vs. 69.73% +/- 5.62%, respectively; P = NS). Significant differences were found between patients of group 2 treated with aspirin alone (69.73% +/- 5.62%), after 2.0 days (60.14% +/- 9.60%; P < 0.05), and after 4.8 +/- 1.3 days (48.37% +/- 11.19%; P < 0.05) with thienopyridine-aspirin. Among 1,684 consecutive stented patients, 16 patients who presented an SAT (group 3) were compared with 30 other stented patients free of SAT (group 4). We found a significant difference between group 3 (63.28% +/- 9.56%) and group 4 (39.80% +/- 10.9%; P < 0.0001). VASP phosphorylation analysis may be useful for the detection of coronary SAT.

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

“…In this publication the authors did not discuss the importance of strict standardisation of the VASP-P assay, which might explain these differing cut-offs: a PRI calculated from the median FI is significantly higher than the PRI calculated from the mean FI (48) as confirmed by our data. The consensus cut-off is based on four publications, two of which used the mean FI to calculate the PRI (11,40), one used the geometric mean FI (21) and another one used the median FI for PRI calculation (41). We are able to show for the first time (ǠTable 2B) that such significant differences in the calculations of PRI also translate into clinically relevant differences in the respective cut-offs.…”

“…The relative risk for MACE in patients without HTPR was 89% lower compared to patients with HTPR. It has previously been proven that the PRI is not influenced by GP-IIb/ IIIa-inhibitors (17) and, moreover, the VASP-P assay has previously been shown to predict MACE including stent thrombosis (11,21,(40)(41)(42). However, knowledge of the predictive value of the VASP-P assay in high-risk STEMI patients is missing except for one recent publication which outlined that the VASP-P assay might be helpful in predicting cardiovascular death above a cut-off of PRI=61% in unselected patients (43).…”

Controversies in Antiplatelet Therapy for Patients With Cardiovascular Disease

“…24 Multiple other possible mechanisms include underdosing, impaired gastric absorption, ADP receptor P 2 Y 12 polymorphisms, and intracellular signaling variability. 25 Increased rates of subacute stent thrombosis 23 and recurrent ischemic events after primary PCI 26 have been noted in clopidogrel nonresponders. However, further work is needed in defining clopidogrel "resistance," measuring it, and correlating it with adverse clinical events before it becomes clinically relevant.…”

High-residual platelet activity despite dual antiplatelet treatment associated with subacute stent thrombosis

“…Despite the accessibility of this treatment, there is still a cohort of patients with major cardiovascular events after successful treatment, and these events seem to be associated with low antiplatelet effect of clopidogrel [7,15,16]. Response variability and resistance to clopidogrel therapy was first reported in 2003 [17].…”