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A Target Trial Emulation to Investigate Kidney Protection from Statin Initiation in Adults with Normal Kidney
Franco W T Cheng1,2,3, Ivy L Mak1, Zoey C T Wong1
1Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Key Points:
Statin initiation in adults with normal kidney function lowered risks of mortality and major adverse kidney events. Statins yielded modest yet clinically meaningful absolute risk reductions for mortality and GFR declines. The observed pleiotropic benefits justified using statins for simultaneous cardiovascular risk reduction and kidney protection.
Background:
Evidence on the kidney-protective effects of statins in individuals with normal kidney function is mixed, with some trials suggesting benefits and others raising concerns about AKI. This study evaluates the effect of statin initiation on kidney function in adults with normal kidney function.
Methods:
Sequential target trial emulation on the basis of electronic health records in the Hong Kong Hospital Authority were conducted. Patients aged 18 year or older with normal kidney function (eGFR ≥60 ml/min per 1.73 m 2 ) who met the indication for statin therapy ( i.e ., LDL-cholesterol ≥100 mg/dl without cardiovascular disease or ≥70 mg/dl with cardiovascular diseases) in Hong Kong between January 2008 and December 2017 were included. Statin initiators and noninitiators were matched using 1:1 propensity score matching. Hazard ratio (HR) and 10-year absolute risk reduction (ARR) of outcomes, including impaired kidney function (eGFR <15 and <60 ml/min per 1.73 m 2 ), kidney function deterioration (≥30% and ≥50% eGFR decline), and all-cause mortality, were estimated using weighted pooled logistic regression on intention-to-treat approach.
Results:
Among 449,595 statin initiators and 449,595 matched noninitiators, statin use was associated with a lower risk of eGFR <15 ml/min per 1.73 m 2 (HR, 0.92 [0.90 to 0.95]; ARR, -0.33% [-0.42% to -0.24%]), eGFR <60 ml/min per 1.73 m 2 (HR, 0.97 [0.96 to 0.98]; ARR, -0.98% [-1.12% to -0.84%]), ≥30% eGFR decline (HR, 0.94 [0.93 to 0.95]; ARR, -1.81% [-2.00% to -1.60%]), ≥50% eGFR decline (HR, 0.90 [0.88 to 0.91]; ARR, -0.98% [-1.11% to -0.85%]), and all-cause mortality (HR [95% confidence interval], 0.90 [0.89 to 0.91]; ARR [95% confidence interval], -1.63% [-1.76% to -1.49%]).
Conclusions:
Statin initiation in adults with normal kidney function was associated with modestly lower all-cause mortality and kidney function impairment, supporting a potential kidney protective benefit of statins without increasing the risks of adverse kidney outcomes.
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