Proteinuria Predicts Resistance to Antiplatelet Therapy in Ischemic Stroke

Abstract

The occurrence of a stroke while on antiplatelet agents presents a therapeutic dilemma. One of the main causes for recurrent strokes is antiplatelet resistance more commonly known as high on treatment platelet reactivity (HTPR). Prior studies have established that proteinuria is associated with HTPR following myocardial infarction. Here, we investigated whether dipstick proteinuria correlates with HTPR in patients presenting with stroke. We performed a retrospective cohort analysis of 102 patients admitted for a recurrent ischemic stroke that had either a VerifyNow aspirin or VerifyNow clopidogrel laboratory test performed to assess platelet reactivity. Dipstick proteinuria was defined as > 30 mg/dl (2+ or more). HTPR was defined as an aspirin resistance unit > 550 for aspirin and a P2Y12 reactivity unit > 208 for clopidogrel. Patients with proteinuria on dipstick were significantly more likely to have HTPR to either aspirin (p value 0.017) or clopidogrel (p value 0.017). After controlling for age, smoking, diabetes, hypertension, CAD and GFR, proteinuria was an independent predictor of HTPR for patient taking aspirin (p = 0.025). Platelet resistance is an entity that undermines the activity of antiplatelet agents in reducing stroke risk. Here, we demonstrate an association with increased platelet reactivity and proteinuria. This highlights a potential new therapeutic target in reducing future stroke risk.

Periprocedural Variability of Platelet Functions in Carotid Artery Stenting: An Analysis Using VerifyNow

“…Various predictors for hypo-response to aspirin such as increased body weight, body mass index, and proteinuria have been reported. 6 , 7) In the present study, co-administration of cilostazol and a higher NASCET degree of stenosis were more frequent in the ARU hypo-response group. A double-blind randomized multi-center trial in Korea revealed that cilostazol add-on to aspirin in ischemic stroke patients made no significant difference in the percentage of aspirin resistance compared to placebo 8) ; however, the mean ARU value before treatment had the tendency to be higher in the cilostazol group.…”

“…This effect is termed "hypo-response," also known as "high on-treatment platelet reactivity" or "resistance." [4][5][6][7][8][9][10][11] Besides, DAPT increases the risk of life-threatening hemorrhagic complications. 12) Therefore, we need to manage DAPT in the optimum range to prevent not only thromboembolic but also hemorrhagic complications.…”

“…The VerifyNow (Accumetrics, Inc., San Diego, CA, USA) assay analyses platelet functions quickly and easily. 4) Many studies using VerifyNow have provided useful evidence about hypo-response to aspirin or clopidogrel, [4][5][6][7][8][9][10][11][13][14][15][16][17] as well as hyper-response to clopidogrel. 4,13,18) Recently, dynamic variability in response to clopidogrel after endovascular treatment has been reported 10,[18][19][20][21][22][23] ; however, individual changes in platelet functions in the short period under DAPT have not been described yet.…”

Antithrombotic Therapy in Patients with Stroke An observational study

“…Thus, proteinuria is an independent predictor of HTPR, but after risk factors such as older age, smoking, diabetes, hypertension. Platelet resistance is a genetic clinical entity that compromises the effectiveness of treatment with antityrombotics and, especially with platelet antiaggregants [23,24].…”

Biomarkers for Antiplatelet Therapies in Acute Ischemic Stroke: A Clinical Review

“…Aspirin resistance can be relevant with the prediction of concentration of proteinuria in patients with AIS, and these are on aspirin therapy. Thus, proteinuria can be considered as a tool in identifying aspirin resistance ( 11 ), and AR is useful as a prognostic marker for cardiovascular disorders and other comorbidities of AIS ( 85 ).…”