Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulationResearch in context

Summary: Background: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). Methods: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.73 m2, ≥30% eGFR decline, and ≥50% eGFR decline) and composite outcomes (all-cause mortality, eGFR <15 mL/min/1.73 m2, and ≥50% eGFR decline) was estimated by pooled logistic regression using intention-to-treat (ITT) and per-protocol (PP) approach. Findings: 1,437,014 eligible person-trials were identified (statin initiators n = 30,907; non-initiators n = 1,406,107), from which 30,892 statin initiators and 108,380 non-initiators were included after propensity-score matching. Relative to non-initiators, significant risk reduction was found among statin initiators in all-cause mortality (HR [95% confidence interval (CI)], ITT: 0.97 [0.95–0.98]; PP: 0.91 [0.88–0.93]), progression to eGFR <15 mL/min/1.73 m2 (ITT: 0.91 [0.89–0.93]; PP: 0.77 [0.74–0.80]), ≥50% eGFR decline (ITT: 0.95 [0.93–0.98]; PP: 0.89 [0.84–0.93]), and composite outcomes (ITT: 0.96 [0.94–0.97]; PP: 0.90 [0.88–0.92]). Statin therapy initiation was also associated significantly with reduced risk of ≥30% eGFR decline using PP approach (0.94 [0.92–0.96]). Interpretation: Over a 10-year follow-up period, initiating statin therapy in patients with CKD was associated with a small yet significant decrease in all-cause mortality and a modest reno-protective effect. Future research should aim to clarify the effects of statin intensity, duration, and adherence. Funding: National Natural Science Foundation of China.