Among 5,178 critically ill patients with acute coronary syndrome across three major ICU databases (MIMIC-IV, eICU, MIMIC-III), early high-intensity statin therapy produced a modest but signal-generating 2.39 percentage-point increase in 7-day severe acute kidney injury (KDIGO stage 2–3) or renal replacement therapy versus moderate-intensity statins (risk ratio 1.16; 95% CI 0.99–1.39). Risk separation sharpened substantially in hemodynamically unstable patients (5.78 pp difference) and those carrying high drug-interaction burdens (6.24 pp). Renal replacement therapy initiation carried a statistically significant 1.33 pp excess risk with high-intensity therapy.
High-intensity statins — rosuvastatin 20–40 mg, atorvastatin 40–80 mg — are guideline-mandated after ACS, yet the ICU environment introduces variables that fixed dosing protocols rarely accommodate: fluctuating renal perfusion, vasopressor use, and polypharmacy. This analysis attempts to operationalize a dynamic safety checkpoint rather than a blanket dose reduction, which is clinically meaningful. The target trial emulation methodology with overlap weighting is methodologically credible for observational data, but residual confounding from unmeasured illness severity remains a real concern. The overall risk difference is narrow and the confidence interval crosses the null, urging caution against overinterpretation. This is a preprint posted to medRxiv and has not yet been peer-reviewed — findings could shift materially after expert scrutiny. Provisionally, this is confirmatory rather than paradigm-shifting, but it argues compellingly for individualized, real-time statin intensity reassessment in ICU-based ACS care.