Consequences of oral antithrombotic use in patients with chronic kidney disease

Abstract

We assessed the risks of bleeding, acute kidney injury (AKI), and kidney failure associated with the prescription of antithrombotic agents (oral anticoagulants and/or antiplatelet agents) in patients with moderate-to-advanced chronic kidney disease (CKD). CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at baseline. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs) for bleeding (identified through hospitalizations), AKI, and kidney failure. Prescriptions of oral antithrombotics were treated as time-dependent variables. At baseline, 339 (11%) patients (65% men; 69 [60-76] years) were prescribed oral anticoagulants only, 1095 (36%) antiplatelets only, and 101 (3%) both type of oral antithrombotics. Over a median (interquartile range [IQR]) follow-up period of 3.0 (IQR, 2.8-3.1) years, 152 patients experienced a bleeding event, 414 patients experienced an episode of AKI, and 270 experienced kidney failure. The adjusted HRs (95% confidence interval [95% CI]) for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were, respectively, 0.74 (95% CI, 0.46-1.19), 2.38 (95% CI, 1.45-3.89), and 3.96 (95% CI, 2.20-7.12). An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR, 1.90, 95% CI, 1.47-2.45) but not the prescription of antiplatelets (HR, 1.24, 95% CI, 0.98-1.56). Kidney failure was not associated with the prescription of oral antithrombotics of any type. This study confirms the high risk of AKI associated with oral anticoagulants prescription in patients with CKD and also highlights the potential aggravating effect of combining vitamin K antagonist (VKA) and antiplatelets on the risk of bleeding.

FIGURE 1

Study flow chart. CKD‐REIN, chronic kidney disease study; eGFR, estimated glomerular filtration rate

FIGURE 2

Description of the bleeding events requiring an emergency department visit or hospital admission, according to type of event and whether or not the event was major (n = 152)

FIGURE 3

Crude and adjusted hazard ratios for bleeding events, according to the prescription of oral antithrombotic agents as a time‐dependent variable in all patients. CI, confidence interval. ^*Adjusted for age, sex, estimated glomerular filtration rate (eGFR; <30 vs. ≥30 ml/min/1.73 m²), serum albumin, cardiovascular history, diabetes, gastrointestinal bleeding history, and number of drugs per patient at baseline. Stroke history, cerebral hemorrhage history, alcohol abuse, lipid‐modifying agent, and selective serotonin reuptake inhibitors were tested in a univariate analysis but did not meet the criteria for inclusion in the multivariable analysis (p = 0.22, 0.25, 0.44, 0.32, and 0.45, respectively). An interaction between antithrombotic treatment and eGFR was statistically significant (p = 0.03)

FIGURE 4

Crude and adjusted hazard ratios for acute kidney injury (AKI) events according to prescriptions of oral anticoagulant and antiplatelet agents as time‐dependent variables in all patients. CI, confidence interval. ^*Adjusted for age, sex, estimated glomerular filtration rate (eGRF), serum albumin, anemia, proteinuria/creatininuria ratio, cardiovascular history, diabetes, history of AKI, number of drugs per patient at baseline, treatment adherence, renin‐angiotensin system inhibitors at baseline, and proton pump inhibitors at baseline. Systolic blood pressure and nonsteroidal anti‐inflammatory drug baseline prescriptions were tested in a univariate analysis but did not meet the criteria for inclusion in the multivariable analysis (p = 0.18 and p = 0.22, respectively). The interaction between oral anticoagulant and antiplatelet was not statistically significant (p = 0.20), as well as the interaction between oral anticoagulant and eGFR (p = 0.30)

FIGURE 5

Crude and adjusted hazard ratios for kidney failure events according to prescriptions of oral anticoagulant and antiplatelet agents as time‐dependent variables in patients with a baseline estimated glomerular filtration rate (eGFR) greater than or equal to 15 ml/min/1.73 m². CI, confidence interval. ^*Adjusted for age, sex, eGFR, body mass index, serum albumin, anemia, proteinuria/creatininuria ratio, systolic blood pressure, cardiovascular history, diabetes, history of acute kidney injury, number of drugs per patient at baseline, treatment adherence, renin‐angiotensin system inhibitors at baseline, diuretics at baseline, and proton pump inhibitors at baseline. The interaction between oral anticoagulant and antiplatelet was not statistically significant (p = 0.51), as well as the interaction between oral anticoagulant and eGFR (p = 0.30)