Impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease patients complicated with end-stage renal disease

Abstract

It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PL_AA) or adenosine diphosphate (PL_ADP), and the P2Y₁₂ reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PL_AA remained unchanged after hemodialysis. In patients taking clopidogrel, the PL_ADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PL_ADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PL_ADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.

Keywords: Antiplatelet therapy; Coronary artery disease; End-stage renal disease; Hemodialysis.

Fig. 1

Platelet activities on different antiplatelet agents before and after hemodialysis. PL_AA represents the pharmacological effects of aspirin (a); PL_ADP and PRU reflect the activity of the P2Y₁₂ receptor and represent the pharmacological effects of clopidogrel (b) and ticagrelor (c). BD before dialysis, AD after dialysis, PL_AA The maximum platelet aggregation rate induced by arachidonic acid, PL_ADP The maximum platelet aggregation rate induced by adenosine diphosphate, PRU P2Y₁₂ reaction unit

Fig. 2

Platelet activities in different groups before and after hemodialysis with different membrane materials. PL_AA represents the pharmacological effects of aspirin (a) before and after hemodialysis with polysulfone or polyamide membrane; PL_ADP and PRU  represent the pharmacological effects of clopidogrel (b) and ticagrelor (c) before and after hemodialysis with polysulfone or polyamide membrane. Asp aspirin, Clop clopidogrel, Tica ticagrelor, PS polysulfone membrane, PA polyamide membrane, BD before dialysis, AD after dialysis, PL_AA the maximum platelet aggregation rate induced by arachidonic acid, PL_ADP the maximum platelet aggregation rate induced by adenosine diphosphate, PRU P2Y₁₂ reaction unit

Fig. 3

Platelet activities and the incidences of drug resistance in ESRD patients and those with NRF. a and b show the aspirin response and the incidence of aspirin resistance in ESRD patients and those with normal renal function. c and d show the clopidogrel response and the incidence of CR in ESRD patients and those with normal renal function; The striped portions represent the proportion of drug resistance. ESRD End-stage renal disease, NRF normal renal function, ESRD-BD patients with end-stage renal disease before dialysis, ESRD-AD patients with end-stage renal disease after dialysis, CR clopidogrel resistance, PL_ADP the maximum platelet aggregation rate induced by adenosine diphosphate, PL_AA the maximum platelet aggregation rate induced by arachidonic acid