Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function

Abstract

Background and objectives: Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established.

Design, setting, participants, & measurements: The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization.

Results: At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m². Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m² per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m² per year among persons receiving aspirin only (P=0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P=0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3).

Conclusions: We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke.

Keywords: Animals; Aspirin; Confidence Intervals; Disease Progression; Humans; Incidence; Models, Animal; Random Allocation; Renal Insufficiency, Chronic; Secondary Prevention; Stroke; Stroke, Lacunar; Ticlopidine; antiplatelet; blood pressure; clopidogrel; creatinine; decline; diabetes mellitus; eGFR; glomerular filtration rate; hypertension.

Figure 1.

Similar trajectories of eGFR during first five years of follow-up in each antiplatelet arm of Secondary Prevention of Small Subcortical Strokes study. Estimates from the generalized estimating equation model with inverse probability of censoring weighting were used to account for study dropout. Median follow-up was 3.1 years.