Statins' Effect on Pneumonia Mortality Murky in Meta-Analysis

SAN DIEGO – Statins may reduce mortality after pneumonia, but this possible benefit may weaken or disappear in important subgroups of patients, results of a double meta-analysis suggest.

The analyses of data from 13 studies including 254,950 adults with pneumonia found a significant 38% decreased likelihood of dying in patients who were on statins compared with non-statin users, before adjusting for confounding factors, Dr. Vineet Chopra and his associates reported at the annual meeting of the Society of Hospital Medicine.

The investigators then pooled adjusted data from the studies accounting for the effects of various confounders, and found a combined reduction in the risk for death after pneumonia of 34% in statin users compared with nonusers, which also was statistically significant, said Dr. Chopra, a hospitalist at the University of Michigan, Ann Arbor.

He and his associates took it a step further, however, and conducted their own subgroup analyses of the studies’ data because of the heterogeneity of the studies and their patient populations, and because most studies used administrative data sets, which often don’t include the severity of illness and other important factors influencing mortality from pneumonia. Authors of 7 of the 13 studies provided unpublished data.

The subgroup analyses done by Dr. Chopra and his colleagues adjusted for the effects of smoking, vaccination status, severity of pneumonia, and whether the studies featured a score for the propensity of a patient to receive statins. They also looked at whether the studies included "uncommon covariates" such as time to antibiotic delivery, the presence of bacteremia, the presence of advance directives, the use of home health services, residence in a nursing home, and measures of frailty other than comorbidity indices.

"When we started teasing out from each model whether or not they adjusted for" any of these potential confounders and pooled the effects separately for each confounder, "any effect of statin use on mortality after pneumonia was completely eliminated," Dr. Chopra said.

A randomized controlled trial will be needed to understand the effects of statins on outcomes in patients with pneumonia, he said. The findings of the current meta-analyses are to be published in the American Journal of Medicine in October, he added.

The meta-analyses included 10 cohort studies (7 retrospective and 3 prospective), 2 case-control studies, and 1 randomized controlled trial published only as an abstract by Korean investigators who did not respond to requests for more information. "I have some doubts about this study," Dr. Chopra said.

The smallest study included 67 patients, and the largest had 121,254 patients. ("This is a nightmare to deal with" in a meta-analysis, he said.) Eight studies focused on hospitalized patients and five on outpatients. Four studies reported only in-hospital mortality, six reported 30-day mortality, two reported 60-day mortality, and one reported mortality 6 months after pneumonia diagnosis.

The variety in study designs and models limits the significance of the meta-analyses’ findings. The observational nature of meta-analyses and the source of data being observational studies also were limitations. In addition, restrictive inclusion criteria were a constraint: The meta-analyses excluded studies of influenza or ventilator-associated pneumonia because the investigators "wanted a pure cohort of community-acquired pneumonia," he said. Sepsis studies in which mortality could not be linked directly to pneumonia also were excluded.

Pneumonia is the eighth-leading cause of death in hospitalized patients. For hospitalists, "pneumonia is our bread and butter," Dr. Chopra said.

The advent of antibiotics greatly reduced mortality from pneumonia, but the drugs have nearly no effect on mortality in the first 5 days of treatment, he said. Sixty-six percent of deaths from pneumonia happen within 7 days of illness.

Inflammation may be an important factor. A recent study found a 15% reduction in the probability of hospital-acquired pneumonia after chest trauma if patients received hydrocortisone therapy (JAMA 2011;305:1242-3).

Statins have anti-inflammatory properties, and several recent studies have reported that statin users had lower risks of developing pneumonia or complications of pneumonia, or of dying of pneumonia (Respir. Res. 2005;6:82; Chest 2007;131:1006-12; Am. J. Med. 2008;121:1002-7; Pharmacoepidemiol. Drug Saf. 2009;18:697-703).

One study of 8,652 veterans found a 46% lower risk of 30-day mortality after pneumonia in statin users compared with nonusers (Eur. Respir. J. 2008;31:611-7).

Some experts have argued that these perceived benefits could all be due to confounding factors and methodological constraints in the studies, prompting the current study.

Dr. Chopra reported having no financial disclosures.

SAN DIEGO – Statins may reduce mortality after pneumonia, but this possible benefit may weaken or disappear in important subgroups of patients, results of a double meta-analysis suggest.

The analyses of data from 13 studies including 254,950 adults with pneumonia found a significant 38% decreased likelihood of dying in patients who were on statins compared with non-statin users, before adjusting for confounding factors, Dr. Vineet Chopra and his associates reported at the annual meeting of the Society of Hospital Medicine.

The investigators then pooled adjusted data from the studies accounting for the effects of various confounders, and found a combined reduction in the risk for death after pneumonia of 34% in statin users compared with nonusers, which also was statistically significant, said Dr. Chopra, a hospitalist at the University of Michigan, Ann Arbor.

He and his associates took it a step further, however, and conducted their own subgroup analyses of the studies’ data because of the heterogeneity of the studies and their patient populations, and because most studies used administrative data sets, which often don’t include the severity of illness and other important factors influencing mortality from pneumonia. Authors of 7 of the 13 studies provided unpublished data.

The subgroup analyses done by Dr. Chopra and his colleagues adjusted for the effects of smoking, vaccination status, severity of pneumonia, and whether the studies featured a score for the propensity of a patient to receive statins. They also looked at whether the studies included "uncommon covariates" such as time to antibiotic delivery, the presence of bacteremia, the presence of advance directives, the use of home health services, residence in a nursing home, and measures of frailty other than comorbidity indices.

"When we started teasing out from each model whether or not they adjusted for" any of these potential confounders and pooled the effects separately for each confounder, "any effect of statin use on mortality after pneumonia was completely eliminated," Dr. Chopra said.

A randomized controlled trial will be needed to understand the effects of statins on outcomes in patients with pneumonia, he said. The findings of the current meta-analyses are to be published in the American Journal of Medicine in October, he added.

The meta-analyses included 10 cohort studies (7 retrospective and 3 prospective), 2 case-control studies, and 1 randomized controlled trial published only as an abstract by Korean investigators who did not respond to requests for more information. "I have some doubts about this study," Dr. Chopra said.

The smallest study included 67 patients, and the largest had 121,254 patients. ("This is a nightmare to deal with" in a meta-analysis, he said.) Eight studies focused on hospitalized patients and five on outpatients. Four studies reported only in-hospital mortality, six reported 30-day mortality, two reported 60-day mortality, and one reported mortality 6 months after pneumonia diagnosis.

The variety in study designs and models limits the significance of the meta-analyses’ findings. The observational nature of meta-analyses and the source of data being observational studies also were limitations. In addition, restrictive inclusion criteria were a constraint: The meta-analyses excluded studies of influenza or ventilator-associated pneumonia because the investigators "wanted a pure cohort of community-acquired pneumonia," he said. Sepsis studies in which mortality could not be linked directly to pneumonia also were excluded.

Pneumonia is the eighth-leading cause of death in hospitalized patients. For hospitalists, "pneumonia is our bread and butter," Dr. Chopra said.

The advent of antibiotics greatly reduced mortality from pneumonia, but the drugs have nearly no effect on mortality in the first 5 days of treatment, he said. Sixty-six percent of deaths from pneumonia happen within 7 days of illness.

Inflammation may be an important factor. A recent study found a 15% reduction in the probability of hospital-acquired pneumonia after chest trauma if patients received hydrocortisone therapy (JAMA 2011;305:1242-3).

Statins have anti-inflammatory properties, and several recent studies have reported that statin users had lower risks of developing pneumonia or complications of pneumonia, or of dying of pneumonia (Respir. Res. 2005;6:82; Chest 2007;131:1006-12; Am. J. Med. 2008;121:1002-7; Pharmacoepidemiol. Drug Saf. 2009;18:697-703).

One study of 8,652 veterans found a 46% lower risk of 30-day mortality after pneumonia in statin users compared with nonusers (Eur. Respir. J. 2008;31:611-7).

Some experts have argued that these perceived benefits could all be due to confounding factors and methodological constraints in the studies, prompting the current study.

Dr. Chopra reported having no financial disclosures.

SAN DIEGO – Statins may reduce mortality after pneumonia, but this possible benefit may weaken or disappear in important subgroups of patients, results of a double meta-analysis suggest.

The analyses of data from 13 studies including 254,950 adults with pneumonia found a significant 38% decreased likelihood of dying in patients who were on statins compared with non-statin users, before adjusting for confounding factors, Dr. Vineet Chopra and his associates reported at the annual meeting of the Society of Hospital Medicine.

The investigators then pooled adjusted data from the studies accounting for the effects of various confounders, and found a combined reduction in the risk for death after pneumonia of 34% in statin users compared with nonusers, which also was statistically significant, said Dr. Chopra, a hospitalist at the University of Michigan, Ann Arbor.

He and his associates took it a step further, however, and conducted their own subgroup analyses of the studies’ data because of the heterogeneity of the studies and their patient populations, and because most studies used administrative data sets, which often don’t include the severity of illness and other important factors influencing mortality from pneumonia. Authors of 7 of the 13 studies provided unpublished data.

The subgroup analyses done by Dr. Chopra and his colleagues adjusted for the effects of smoking, vaccination status, severity of pneumonia, and whether the studies featured a score for the propensity of a patient to receive statins. They also looked at whether the studies included "uncommon covariates" such as time to antibiotic delivery, the presence of bacteremia, the presence of advance directives, the use of home health services, residence in a nursing home, and measures of frailty other than comorbidity indices.

"When we started teasing out from each model whether or not they adjusted for" any of these potential confounders and pooled the effects separately for each confounder, "any effect of statin use on mortality after pneumonia was completely eliminated," Dr. Chopra said.

A randomized controlled trial will be needed to understand the effects of statins on outcomes in patients with pneumonia, he said. The findings of the current meta-analyses are to be published in the American Journal of Medicine in October, he added.

The meta-analyses included 10 cohort studies (7 retrospective and 3 prospective), 2 case-control studies, and 1 randomized controlled trial published only as an abstract by Korean investigators who did not respond to requests for more information. "I have some doubts about this study," Dr. Chopra said.

The smallest study included 67 patients, and the largest had 121,254 patients. ("This is a nightmare to deal with" in a meta-analysis, he said.) Eight studies focused on hospitalized patients and five on outpatients. Four studies reported only in-hospital mortality, six reported 30-day mortality, two reported 60-day mortality, and one reported mortality 6 months after pneumonia diagnosis.

The variety in study designs and models limits the significance of the meta-analyses’ findings. The observational nature of meta-analyses and the source of data being observational studies also were limitations. In addition, restrictive inclusion criteria were a constraint: The meta-analyses excluded studies of influenza or ventilator-associated pneumonia because the investigators "wanted a pure cohort of community-acquired pneumonia," he said. Sepsis studies in which mortality could not be linked directly to pneumonia also were excluded.

Pneumonia is the eighth-leading cause of death in hospitalized patients. For hospitalists, "pneumonia is our bread and butter," Dr. Chopra said.

The advent of antibiotics greatly reduced mortality from pneumonia, but the drugs have nearly no effect on mortality in the first 5 days of treatment, he said. Sixty-six percent of deaths from pneumonia happen within 7 days of illness.

Inflammation may be an important factor. A recent study found a 15% reduction in the probability of hospital-acquired pneumonia after chest trauma if patients received hydrocortisone therapy (JAMA 2011;305:1242-3).

Statins have anti-inflammatory properties, and several recent studies have reported that statin users had lower risks of developing pneumonia or complications of pneumonia, or of dying of pneumonia (Respir. Res. 2005;6:82; Chest 2007;131:1006-12; Am. J. Med. 2008;121:1002-7; Pharmacoepidemiol. Drug Saf. 2009;18:697-703).

One study of 8,652 veterans found a 46% lower risk of 30-day mortality after pneumonia in statin users compared with nonusers (Eur. Respir. J. 2008;31:611-7).

Some experts have argued that these perceived benefits could all be due to confounding factors and methodological constraints in the studies, prompting the current study.

Dr. Chopra reported having no financial disclosures.