Inhaled Steroids Lower All-Cause Mortality in COPD

WINNIPEG, Manitoba, Sept. 13 -- Inhaled corticosteroids sharply reduce the risk of death from all causes for patients with chronic obstructive pulmonary disease (COPD), according to researchers here.

COPD patients 65 or older had a 25% risk reduction in all-cause mortality between 90 and 365 days after discharge if they were using inhaled corticosteroids, according to Christine Macie, M.D., then at the University of Manitoba and now at Cambridge Memorial Hospital in Cambridge, Ontario.

Younger patients -- ages 35 to 64 -- had a 53% reduction in mortality risk, Dr. Macie and colleagues reported in the September issue of CHEST.

The findings, derived from a large-scale pharmaco-epidemiologic study here, are consistent with several other studies that have reported mortality risk reductions associated with the use of inhaled corticosteroids, Dr. Macie and colleagues noted.

But in this study the reduction in the overall risk in both age groups was mainly driven by a significant reduction in cardiovascular events among patients treated with inhaled corticosteroids, the researchers found. The use of inhaled corticosteroids reduced deaths attributable to COPD, but not significantly so.

The researchers took advantage of the universal Manitoba health care system, which allowed them to identify all patients 35 or older admitted to hospital in the province from April 1, 1996, to March 31, 2000, who were later discharged with a primary diagnosis of COPD.

Pharmacy records and a population registry were also linked to the database, allowing the researchers to identify patients taking inhaled corticosteroids, bronchodilators, or neither, and to ascertain causes of death.

The study found 5,491 eligible patients, but 604 died with 90 days of discharge and were excluded from the study. Of the remainder, 1,007 (18.0%) were 35 to 64 years old and 4,584 (82.0%) were older.

The age groups were divided into those who were given inhaled corticosteroids and those who weren't, Dr. Macie and colleagues reported, and they were compared for the primary variable -- death from any cause between 90 and 365 days after discharge. The study also compared those given bronchodilators, with or without steroids, with those who did not get bronchodilators, with or without steroids.

The researchers also conducted a nested case-control study, using the same population, in which patients who died within 90 to 365 days of discharge were compared with respect to inhaled corticosteroids exposure before death with age-matched and gender-matched controls who had survived to the same point.

The study found:

• For patients 65 or older, the use of inhaled corticosteroids led to a relative risk reduction of 0.75, with a 95% confidence interval from 0.61 to 0.91.
• For the younger group, the relative risk reduction was 0.47, with a 95% confidence interval from 0.23 to 0.98.
• Compared to those who were given bronchodilators, the use of inhaled corticosteroids at any age resulted in a 23% reduction in risk, with a 95% confidence interval from 6% to 37%.
• The reduction in risk for death from cardiovascular events was significant: compared to those getting bronchodilators, the risk was reduced by 38%, with a 95% confidence interval from 11% to 57%.
• The medications also reduced the risk of COPD death, but the reduction was not significant.

The effect of the medication was most evident in the short term, Dr. Macie and colleagues found, with significant reductions in all-cause, COPD, and cardiovascular mortality for patients who got inhaled corticosteroids within 30 days of discharge but this was not the case for greater time intervals.

"Our results indicate that the effect of inhaled corticosteroids is relatively short-term and that those currently using them are relatively better protected," Dr. Macie said. "Inhaled corticosteroids should be prescribed as soon as clinically indicated."

In an accompanying editorial, Don Sin, M.D., and Paul Man, M.D., both of St. Paul's Hospital in Vancouver, British Columbia, said the findings add to the weight of evidence that inhaled corticosteroids are beneficial in COPD, but "should not be considered definitive."

Like all database studies, they wrote, the study is subject to residual or external confounding. Also, the researchers were unable to confirm diagnoses of COPD or to stratify the study population according to the severity of disease.

Despite that, they argued, the study adds to the evidence that COPD can be treated with inhaled corticosteroids, raising the "tantalizing possibility" of reducing the risk of death associated with the disease.

But it's still too early to incorporate the notion into routine clinical practice, until more is understood about the mechanism of any benefit, they argued.

Dr. Macie and colleagues did not report any conflicts in interest, but both Dr. Sin and Dr. Man have received honoraria and research funding from GlaxoSmithKline and AstraZeneca, both of which make inhaled corticosteroids.