Background
The high heterogeneity of ARDS contributes to paradoxical conclusions from previous investigations of rosuvastatin for ARDS. Identification of the population (phenotype) who could benefit from rosuvastatin is a novel exploration for precise treatment of ARDS.
Methods
The patient population for this analysis consisted of unique patients with ARDS enrolled in the SAILS trial (Rosuvastatin vs. Placebo). Phenotypes were derived using consensus k means clustering applied to routinely available clinical variables within 6 hours of hospital presentation before receiving placebo or rosuvastatin. Kaplan–Meier statistic was used to estimate the 90 day cumulative mortality for screening specific population who could benefit from rosuvastatin, with cut-off value as P <0.05.
Results
The derivation cohort included 585 patients with ARDS. Of the 4 derived phenotypes, phenotype 3 was identified as "specific population who could benefit from rosuvastatin" since rosuvastatin resulted in a significant reduction in 90 day cumulative mortality for ARDS (hazard ratio [HR] 0.29 [95% CI 0.09, 0.93]; P=0.027). Meanwhile, there were no significant differences in baseline characteristics between those assigned to rosuvastatin and those assigned to placebo. Additionally, rosuvastatin markedly improved the free of cardiovascular failure (10.08±3.79 in Rosuvastatin group vs 7.31±4.94 in Placebo group, P=0.01) and coagulation abnormality (13.65±1.33 vs 12.15±3.77, P=0.02) to day 14 in phenotype 3. Patients classified as phenotype 3 exhibited but not limited to the relative higher platelet count (390.05±79.43×10^9/L), lower CRP (20.23±11.99μg/L) and Creat (1.42±1.08 mg/dl), compared with patients classified as other phenotypes. Besides that, rosuvastatin seemed to increase 90 day mortality for patients in phenotype 4 (HR 2.76[95% CI 0.09, 9.93], P=0.076), with its adverse effect on the reduction of free of renal failure to day 14(4.70±4.99 vs 10.17±4.69, P=0.01). Patients in phenotype 4 showed a relative severe illness baseline features particularly renal failure.
Conclusions
This secondary analysis of SAILS trial identified the specific population who can benefit from rosuvastatin using machine learning applied to clinical variables at the time of hospital presentation, which uncovered a novel value of rosuvastatin for the treatment of ARDS, with validation clinical trials to be warranted to assess these further.