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Rebuttal From Drs Mermis and SimpsonRebuttal From Drs Mermis and Simpson FREE TO VIEW

Joel D. Mermis, MD; Steven Q. Simpson, MD, FCCP
Author and Funding Information

From the Division of Pulmonary and Critical Care Medicine, University of Kansas School of Medicine.

CORRESPONDENCE TO: Steven Q. Simpson, MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of Kansas School of Medicine, 3901 Rainbow Blvd, Mail Stop 3007, Kansas City, KS 66160; e-mail: ssimpson3@kumc.edu


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(6):1436-1437. doi:10.1378/chest.14-2226
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We agree that the pleotropic effects of statins provide mechanistic plausibility for treating critically ill patients. However, over the past decades, we have been baited with mechanistically promising antiinflammatory and other treatments, such as anti-tumor necrosis factor therapies, IL-1ra, and drotrecogin α, which have all failed to benefit patients. We are, sadly, left without specific therapies for common critical illnesses, such as sepsis or ARDS. Understandably, we are eager for new therapies.

Drs Flannery and Kruger1 point out that discontinuing a patient’s statin medication at ICU admission could result in inadvertently not resuming the medication at ICU or hospital discharge. In the modern era of electronic medical records and pharmacist-driven medicine reconciliation, data demonstrate that this is less of a concern.2 Therefore, the decision really concerns the risk-benefit of continuing the medication during a patient’s critical illness.

Our opponents cite multiple studies that provide support for continuation of statins in several critical illnesses, including candidemia, sepsis, ventilator-associated pneumonia, and delirium. We believe that their conclusions overstate the current evidence. Nearly all these studies supporting statin continuation evaluated a small population and were observational in nature. Observational studies evaluating potential benefits of statin use across a broad range of indications have been contradictory in their results and risk healthy user bias. Such reports have suggested that statins reduce the risk of a broad range of diseases, including infection, fractures, VTE, and other illnesses, but a large study of > 129,000 patients taking statins found that all these reported benefits were attributable to selection bias and confounding.3

Similarly, the promise for statin use in critically ill patients provided by observational studies has been dispelled by more rigorous studies that closely examined for healthy user bias. For example, one nested cohort study and one observational study suggested that statin continuation provided mortality benefit.4,5 However, a study in 1,895 patients on statins examining for healthy user bias in the 354 patients in whom statins were continued following admission for pneumonia and sepsis found the mortality benefit no longer evident after propensity scoring accounted for the impact of healthy user bias.6 Although a few reports suggested that statins provide protection against ICU delirium, these studies are again observational. For now, we feel compelled to rely on high-level evidence, specifically randomized controlled trials. In one randomized trial, prior statin users continued on statins in the ICU demonstrated a 28-day mortality reduction, which is of questionable benefit because the same cohort of patients did not experience reduced Sequential Organ Failure Assessment scores, hospital lengths of stay, or 90-day mortality.

Although the benefit of statin continuation in critically ill patients is not proven, the two largest randomized trials evaluating statins in critically ill patients demonstrate hazard. The Rosuvastatin in Sepsis-Induced Acute Respiratory Distress Syndrome trial demonstrated increased risk of renal and hepatic dysfunction, and the Statins and Ventilator-Associated Pneumonia study was stopped for futility after simvastatin demonstrated a 6% absolute increase in 28-day mortality.7,8 High-level evidence of benefit from statin continuation is lacking, whereas safety concerns remain. We recommend discontinuing statins on ICU admission in critically ill patients.

References

Flannery AH, Kruger PS. Point: should patients receiving statins prior to ICU admission be continued on statin therapy? Yes. Chest. 2014;146(6):1431-1433.
 
Conklin JR, Togami JC, Burnett A, Dodd MA, Ray GM. Care transitions service: a pharmacy-driven program for medication reconciliation through the continuum of care. Am J Health Syst Pharm. 2014;71(10):802-810. [CrossRef] [PubMed]
 
Smeeth L, Douglas I, Hall AJ, Hubbard R, Evans S. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol. 2009;67(1):99-109. [CrossRef] [PubMed]
 
Al Harbi SA, Tamim HM, Arabi YM. Association between statin therapy and outcomes in critically ill patients: a nested cohort study. BMC Clin Pharmacol. 2011;11:12. [CrossRef] [PubMed]
 
Bruyere R, Vigneron C, Prin S, et al. Impact of prior statin therapy on the outcome of patients with suspected ventilator-associated pneumonia: an observational study. Crit Care. 2014;18(2):R83. [CrossRef] [PubMed]
 
Yende S, Milbrandt EB, Kellum JA, et al. Understanding the potential role of statins in pneumonia and sepsis. Crit Care Med. 2011;39(8):1871-1878. [CrossRef] [PubMed]
 
Truwit JD, Bernard GR, Steingrub J, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191–-2200. [CrossRef] [PubMed]
 
Papazian L, Roch A, Charles PE, et al; STATIN-VAP Study Group. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA. 2013;310(16):1692-1700. [CrossRef] [PubMed]
 

Figures

Tables

References

Flannery AH, Kruger PS. Point: should patients receiving statins prior to ICU admission be continued on statin therapy? Yes. Chest. 2014;146(6):1431-1433.
 
Conklin JR, Togami JC, Burnett A, Dodd MA, Ray GM. Care transitions service: a pharmacy-driven program for medication reconciliation through the continuum of care. Am J Health Syst Pharm. 2014;71(10):802-810. [CrossRef] [PubMed]
 
Smeeth L, Douglas I, Hall AJ, Hubbard R, Evans S. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol. 2009;67(1):99-109. [CrossRef] [PubMed]
 
Al Harbi SA, Tamim HM, Arabi YM. Association between statin therapy and outcomes in critically ill patients: a nested cohort study. BMC Clin Pharmacol. 2011;11:12. [CrossRef] [PubMed]
 
Bruyere R, Vigneron C, Prin S, et al. Impact of prior statin therapy on the outcome of patients with suspected ventilator-associated pneumonia: an observational study. Crit Care. 2014;18(2):R83. [CrossRef] [PubMed]
 
Yende S, Milbrandt EB, Kellum JA, et al. Understanding the potential role of statins in pneumonia and sepsis. Crit Care Med. 2011;39(8):1871-1878. [CrossRef] [PubMed]
 
Truwit JD, Bernard GR, Steingrub J, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191–-2200. [CrossRef] [PubMed]
 
Papazian L, Roch A, Charles PE, et al; STATIN-VAP Study Group. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA. 2013;310(16):1692-1700. [CrossRef] [PubMed]
 
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