Simvastatin ineffective in acute respiratory distress syndrome [HARP-2 trial]

1. When compared with placebo, simvastatin did not significantly reduce the number of ventilator-free days in patients presenting with acute respiratory distress syndrome.

2. Moreover, simvastatin did not significantly reduce 28-day mortality as compared with placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Acute respiratory distress syndrome (ARDS) refers to a spectrum of illnesses characterized by respiratory failure, often requiring mechanical ventilation. The PaO2 to FiO2 ratio (PF ratio) is often used to diagnose ARDS and assess severity. While a previous randomized controlled trial suggested that simvastatin reduced nonpulmonary organ dysfunction in ARDS, the trial was limited to a single centre and was underpowered to assess the effect on clinical outcomes. The purpose of this study was to determine if simvastatin treatment would improve clinical outcomes in patients presenting with ARDS irrespective of etiology.

In summary, this trial found that simvastatin treatment was not associated with any significant reductions in ventilator-free days when compared with placebo (mean difference 1.1 days; 95%CI -0.6 to 2.8). Moreover, there were no significant differences in 28-day mortality (RR 0.8; 95%CI 0.6-1.1). A strength of this study was its heterogeneous study population. By including all patients with ARDS regardless of cause, the findings are more generalizable. The findings of this study, taken along with the results from the Statins for Acutely Injured Lungs from Sepsis (SAILS) trial, suggest that there is little value in using statins to treat ARDS.

Click to read the study, published today in NEJM

Relevant Reading: Rosuvastatin for sepsis-associated acute respiratory distress syndrome

In-Depth [randomized, controlled study]: This study was conducted in 40 intensive care units across the United Kingdom and Ireland. Patients were eligible if they were intubated and ventilated within 48 hours after the onset of ARDS (i.e., PF ratio ≤300 mmHg). Exclusion criteria included age <16 years, pregnancy, severe renal impairment, severe liver disease, and treatment with statins in the 2 weeks prior to randomization. A total of 540 patients were randomized to receive either simvastatin 80 mg daily or placebo. The primary outcome measure was the number of ventilator-free days to day 28. Secondary outcomes included change in the oxygenation index and Sequential Organ Failure Assessment (SOFA) score, and 28-day mortality.

There were no significant differences between the two groups in the number of ventilator-free days (mean difference 1.1 days; 95%CI -0.6 to 2.8). After adjusting for baseline PF ratio, there was still no significant difference in ventilator-free days (mean difference 1.4 days; 95%CI -0.3 to to 3.2). The two groups were not significantly different in terms of change in oxygenation index or SOFA score. Moreover, there was no significant difference between the groups in terms of 28-day mortality (RR 0.8; 95%CI 0.6-1.1).

Image: PD

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