Effects of Endothelial Dysfunction on Residual Platelet Aggregability After Dual Antiplatelet Therapy With Aspirin and Clopidogrel in Patients With Stable Coronary Artery Disease

Abstract

Background-Dual antiplatelet therapy with aspirin and clopidogrel is widely used in patients with coronary stents. High residual platelet reactivity (high RPR) after dual antiplatelet therapy is associated with increased cardiovascular events. Endothelial function could affect platelet reactivity in vivo. We hypothesized that endothelial dysfunction could be associated with high RPR after dual antiplatelet therapy in patients with stable coronary artery disease. Methods and Results-We screened patients with stable coronary artery disease for cytochrome P450 (CYP) 2C19 genotypes and enrolled 103 patients who lacked CYP2C19*2 or *3 loss-of-function allele to minimize the effect of this gene on high RPR. All patients received aspirin (100 mg/d) and clopidogrel (75 mg/d for long-term treatment or a loading dose of 300 mg) before the following tests. Platelet aggregability was assessed as P2Y12 reaction unit using the VerifyNow System. High RPR was defined as P2Y12 reaction unit ≥230. Peripheral endothelial function was expressed as reactive hyperemia index using reactive hyperemia peripheral arterial tonometry. Fifty-three patients exhibited high RPR. High RPR patients were significantly older, had higher levels of B-type natriuretic peptide, and were predominantly hypertensive compared with non-high RPR patients.

Assessment of platelet‐derived thrombogenicity with the total thrombus‐formation analysis system in coronary artery disease patients receiving antiplatelet therapy

“…The sample size was calculated on the basis of previous reports that assessed PRU levels in Japanese CAD patients [23,24]. On the basis of the proportions of patients in our hospital, we estimated that the study subjects should include eight patients who were not treated with clopidogrel for every 10 patients treated with aspirin/clopidogrel.…”

Utility of Noninvasive Endothelial Function Test for Prediction of Deep Vein Thrombosis After Total Hip or Knee Arthroplasty

“…In this study, the RHI showed a negative correlation with the Framingham risk score and was associated with postoperative DVT independently of the Framingham risk score, DVT-related traditional risk factors, and Qthrombosis risk score. We suspect that the RHI could be associated with VTE through cardiovascular disease risk factors, including unknown factors, 8,21,44, 45 and also through intrinsic properties of the venous endothelium. It has been reported that 894 G>T polymorphism in the endothelial nitric oxide synthase gene is associated with endothelial dysfunction and the risk of VTE.…”

Secondary Prevention Strategy of Cardiovascular Disease Using Endothelial Function Testing

“…43 Moreover, in patients with CAD on dual antiplatelet therapy, peripheral endothelial function as assessed by RH-PAT is associated with residual platelet reactivity that may also contribute to an increased risk of in-stent thrombosis. 44 Both systemic and local endothelial dysfunction may be modifiable factors in the prevention of in-stent thrombosis, and several stent technologies are being developed in an attempt to decrease the risk of late thrombotic events, including bioabsorbable polymers, nonpolymeric stent surfaces, bioabsorbable stents, and an EPC capture stent. Possible mechanisms involved in the pathogenesis of instent restenosis include platelets and inflammatory cell activation by procedural vascular injury with subsequent local release of cytokines and growth factors, leukocyte adherence, smooth muscle cell proliferation, and extracellular matrix synthesis.…”