Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial

Publication date: Available online 2 August 2018Source: The Lancet Respiratory MedicineAuthor(s): Carolyn S Calfee, Kevin L Delucchi, Pratik Sinha, Michael A Matthay, Jonathan Hackett, Manu Shankar-Hari, Cliona McDowell, John G Laffey, Cecilia M O'Kane, Daniel F McAuley, Andrew J Johnston, Archana Paikray, Cat Yates, Petra Polgarova, Esther Price, Amy McInerney, Katarzyna Zamoscik, Ged Dempsey, Colette Seasman, Lynn GilfeatherSummaryBackgroundPrecision medicine approaches that target patients on the basis of disease subtype have transformed treatment approaches to cancer, asthma, and other heterogeneous syndromes. Two distinct subphenotypes of acute respiratory distress syndrome (ARDS) have been identified in three US-based clinical trials, and these subphenotypes respond differently to positive end-expiratory pressure and fluid management. We aimed to investigate whether these subphenotypes exist in non-US patient populations and respond differently to pharmacotherapies.MethodsHARP-2 was a multicentre, randomised controlled trial of simvastatin (80 mg) versus placebo done in general intensive care units (ICUs) at 40 hospitals in the UK and Ireland within 48 h of onset of ARDS. The primary outcome was ventilator-free days, and secondary outcomes included non-pulmonary organ failure-free days and mortality. In a secondary analysis of HARP-2, we applied latent class analysis to baseline data without consideration of outcomes to identify subphenotypes, and we compared clinical o...
Source: The Lancet Respiratory Medicine - Category: Respiratory Medicine Source Type: research