COMMENTARY

How Useful Are Statins for Treating Acute Lung Injury?

Greg Martin, MD

Disclosures

October 07, 2011

A Randomized Clinical Trial of Hydroxymethylglutaryl–Coenzyme A Reductase Inhibition for Acute Lung Injury (The HARP Study)

Craig TR, Duffy MJ, Shyamsundar M, et al
Am J Respir Crit Care Med. 2011;183:620-626

Study Summary

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are related forms of severe edematous lung injury with high morbidity and mortality and reported incidence of 15%-20% in patients ventilated for more than 24 hours.[1] Hydroxylmethylglutaryl coenzyme A reductase inhibitors (statins) may be beneficial in either preventing or treating ALI/ARDS because they directly alter some of the mechanisms involved in this condition.[2]

The authors sought to determine whether statins favorably impact the physiology and biology involved in ALI by randomly assigning 60 patients with ALI to receive 80 mg of simvastatin or a placebo for up to 14 days or until extubated. Simvastatin was well tolerated, with no increase in adverse events. There was no difference in extravascular lung water, a measure of pulmonary edema, by day 7, but the simvastatin group had decreased interleukin-8 in bronchoalveolar lavage fluid and improvements in nonpulmonary organ dysfunction by day 14. Intensive care unit mortality was 30% in both groups. The authors conclude that treatment with simvastatin is safe and may improve organ dysfunction in ALI through reductions in pulmonary and systemic inflammation.

Viewpoint

This study extends a long history of the investigation of statins for preventing or treating ALI/ARDS, which includes animal models and early human studies.[3,4] These findings are particularly important for a condition where no direct pharmacologic therapy exists to treat the condition, and where mortality has remained elevated for decades.[5] However, as a small pilot study these results are not sufficient to change clinical practice, but they are encouraging, even in the face of recent observational data suggesting that statins may not beneficially affect ALI/ARDS or related organ dysfunction.[6]

Larger studies planned by this group and ongoing studies by the ARDS Network will help to answer this question in the not-too-distant future.[7] The challenge to answering this question will be (at least) 2-fold. The first challenge is the complexity of the clinical condition -- there are numerous causes of ALI/ARDS, with variable timing of onset and heterogeneity in outcomes that are at least partially caused by coexisting medical conditions that inevitably alter care and outcomes. These challenges can be managed in the environment of a randomized, controlled clinical trial, but they limit the application in a real-world setting. The other problem is considering whether statins are most effective in preventing ALI/ARDS before it occurs, or treating it once the ALI/ARDS has become established. The mechanisms involved in prevention and treatment of ALI/ARDS are different and statins may not work for both problems. Of course, preventing all cases of ALI/ARDS is attractive, but unlikely, so developing therapeutics for this potentially lethal disease remains important.

Abstract

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