Prior statin use is associated with improved outcomes in community-acquired pneumonia.

Evidence for the pleiotrophic benefits of statins continues to mount. This recent paper published by Chalmers et al. adds to the growing evidence that the use of statins belongs to all physicians, not just cardiologists, and now it is the turn of the pulmonologist/intensivist to reap the benefits.

Community-acquired pneumonia (CAP) continues to be a leading cause of mortality and morbidity in both the developed and developing world. There has been improvement in outcomes since the introduction of antibiotics in the 1940s; however, 10-20% of patients hospitalised for CAP still require admission to the ICU, with a mortality of 20-50% in these patients {1,2}. With emerging antimicrobial resistance and few new antibiotics in development, any adjunctive treatment that shows benefit could have a significant role to play in the management of this common condition. Chalmers et al. have provided us with a prospective observational study of patients admitted with CAP. The primary outcome was 30-day mortality, with secondary outcomes including the need for mechanical ventilation, inotropic support, development of empyema/parapneumonic effusions and C-reactive protein levels on day 4. Using multivariate logistic regression, patients with prior statin use had lower 30-day mortality (adjusted odds ratio (AOR) 0.46, 95% CI: 0.25-0.85, p=0.01) and developed complicated pneumonia less frequently (AOR 0.44, 95% CI: 0.25-0.76, p=0.0060). Prior statin use was not associated with reduction in requirements for inotropic support or invasive ventilation. Also of interest is that those patients who had previously been prescribed statins had more severe pneumonia, as indicated by a higher Pneumonia Severity Index (PSI) score (PSI 4 compared with PSI 3). This makes the improved outcome seen in those patients with prior statin use even more relevant. It was also found that patients in the statin group had C-reactive protein levels on admission that were lower (median 119mg/L, IQR 46-215) than those of patients prescribed other cardiovascular drugs (176mg/L, IQR 67-290) or no cardiovascular drugs (182mg/L, IQR 66-326), p<0.0001. Statin use was also found to be independently protective against a C-reactive protein that failed to decrease by 50% or more at day 4 (AOR 0.52, 95% CI: 0.30-0.89, p=0.02).

The authors were aware of the potential of benefit being due to "healthy user effect" and, therefore, also correlated the outcome for patients taking other cardiovascular drugs (aspirin, beta blockers, ACE inhibitors, and angiotensin II antagonists) that may also have had these benefits, to allow for comparison. Prior use of these drugs was not associated with statistically significant benefit, and, furthermore, prior beta-blocker use was associated with independent higher 30-day mortality and an increased risk for invasive ventilation or inotropic support. This is not the first study to have investigated the effect of prior statin use on pneumonia outcomes. There have been three retrospective studies which showed improved outcome in patients taking statins {3-5}. Another recently published study showed further statin benefit in a large population-based cohort study of 29,900 adults hospitalised with pneumonia in Northern Denmark. Mortality among statin users was shown to be 10.3% versus 15.7% after 30 days and 16.8% versus 22.4% after 90 days, with corresponding adjusted 30- and 90-day mortality rate ratios of 0.69 (95% CI: 0.58-0.82) and 0.75 (0.65-0.86) {6}. These positive studies need to be counterbalanced by at least one negative population-based prospective cohort study which showed no reduced mortality or need for admission to the ICU in patients with pneumonia {7}. The exact mechanism of these benefits, should they be real, have not been fully identified, but there is evidence that statins reduce cytokine levels together with other inflammatory markers in cardiac patients {8}, and it is postulated that the improved outcome is due to the anti-inflammatory and immunomodulatory effects of the statins. A number of questions still remain that hopefully will be addressed by ongoing studies, including a consideration of how statins would perform when prescribed for the first time as part of the initial management, together with antibiotics, in patients with CAP.

References: {1} Fine et al. JAMA 1996, 275:134-41 [PMID:8531309]. {2} Kaplan et al. Am J Respir Crit Care Med 2002, 165:766-72 [PMID:11897642]. {3} Schlienger et al. Pharmacotherapy 2007, 27:325-32 [PMID:17316144]. {4} Mortensen et al. Eur Respir J 2008, 31:611-7 [PMID:17959631]. {5} Mortensen et al. Respiratory Research 2005, 6:82 [PMID:16042797]. {6} Thomsen et al. Arch Intern Med 2008, 168:2081-7 [PMID:18955636]. {7} Majumdar et al. BMJ 2006, 333:999 [PMID:17060337]. {8} Strandberg et al. Lancet 1999, 353:118-9 [PMID:10023901].