High Platelet Reactivity on Clopidogrel Therapy Correlates With Increased Coronary Atherosclerosis and Calcification

Abstract

OBJECTIVES To evaluate the relationship between platelet reactivity and atherosclerotic burden in patients undergoing percutaneous coronary intervention (PCI) with pre-intervention volumetric intravascular ultrasound (IVUS) imaging. BACKGROUND Atherosclerosis progresses by the pathologic sequence of sub-clinical plaque rupture, thrombosis and healing. In this setting, increased platelet reactivity may lead to more extensive arterial thrombosis at the time of plaque rupture, leading to a more rapid progression of the disease. Alternatively, abnormal vessel wall biology with advanced atherosclerosis is known to enhance platelet reactivity. Therefore, it is possible that by either mechanism, increased platelet reactivity may be associated with greater atherosclerotic burden. METHODS We analyzed patients who underwent PCI with pre-intervention IVUS imaging and platelet reactivity functional assay (P2Y12 reaction-units [PRU]) performed >16 hours post-PCI after stabilization of clopidogrel therapy (administered pre-PCI). A PRU value of >230 defined high on-treatment platelet reactivity (HPR). RESULTS Among 335 patients (mean age 65.0; 71% male), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with HPR being associated with diabetes and chronic renal insufficiency. By IVUS analysis, HPR patients had significantly greater target lesion calcium length, calcium arc, and calcium index. Furthermore, HPR patients tended to have longer lesions and greater volumetric dimensions, indicating higher plaque volume, larger total vessel volume and also greater lumen volume, despite similar plaque burden. By multivariable analysis controlling for baseline clinical variables, HPR was the single consistent predictor of all IVUS parameters examined, including plaque volume, calcium length and calcium arc. CONCLUSIONS Increased platelet reactivity on clopidogrel treatment, as defined by a PRU value of >230, is associated with greater coronary artery atherosclerotic disease burden and plaque calcification.

Resistant in‐stent restenosis in the drug eluting stent era

“…Our hypothesis is supported by the fact that 62% of our population suffered from diabetes and 52% showed moderate to severe calcification. These are established vasculopathy markers that are directly related to increased inflammation and enhanced platelet reactivity . Additionally, the presence of severely calcified lesions adversely affects optimal stent deployment, leading to under‐expansion, malapposition, and polymer damage .…”

Prognostic impact of high residual platelet reactivity after chronic total occlusion percutaneous coronary intervention in patients with diabetes mellitus

“…Previous studies on PCI in diabetic patients have shown an increased mortality in insulin-requiring DM patients and the reported long-term mortality rates are < 30% [4][5][6]34]. No study focused on the incremental risk associated with HRPR in diabetics, while an intravascular ultrasound study documented a relationship between HRPR and coronary atherosclerotic burden [35]. The results of our study show that the assessment of platelet reactivity while on clopidogrel treatment is clinically relevant, since it allows for the identification of patients at very high risk of cardiac death.…”

Clopidogrel response variability is associated with endothelial dysfunction in coronary artery disease patients receiving dual antiplatelet therapy

“…This was also observed when intravascular ultrasound was applied in patients with CAD under clopidogrel treatment [33] or in patients with stable CAD undergoing elective PCI which might partly account for higher risk of periprocedural myocardial infarction [34]. Though, this observation may be an epiphenomenon such as the increased number of atherosclerotic lesions in patients with diabetes mellitus [35,36].…”