SAN DIEGO — In patients with chronic obstructive pulmonary disease (COPD), simvastatin has no effect on the number of exacerbations, according to a new prospective analysis.
This finding conflicts with results from retrospective trials that have shown a protective effect of statins.
"Thousands of patients worth of observational data" suggested that simvastatin would have an independent effect on the rate of COPD exacerbations, said Gerard Criner, MD, professor of medicine and director of critical care and pulmonary care medicine at the Temple University School of Medicine in Philadelphia.
The researchers conducted the Simvastatin Therapy for Moderate and Severe COPD (STATCOPE) trial to determine if this was true, he explained.
The results, presented here at the American Thoracic Society (ATS) 2014 International Conference, were published online simultaneously in the New England Journal of Medicine.
The randomized placebo-controlled trial compared simvastatin with placebo in 885 patients with COPD.
Participants had a smoking history of 10 or more pack-years (mean, 50.6 years) and had received supplemental oxygen, glucocorticoid treatment, antibiotic treatment, or hospital or emergency department treatment for COPD in the previous year.
Patients with diabetes or cardiovascular disease were excluded from the study, as were patients already taking statins or who should have been prescribed statins on the basis of Adult Treatment Panel III criteria.
The primary end point — annual exacerbation rate — was similar in the simvastatin and placebo groups.
Table 1. Outcomes
| Outcome | Simvastatin | Placebo | P Value |
| Mean number of COPD exacerbations per person-year | 1.36 | 1.39 | .54 |
| Median time to first exacerbation | 223 days | 231 days | .34 |
| Number of deaths | 28 | 30 | .89 |
The data safety and monitoring board stopped the trial before enrollment was complete because there was no apparent therapeutic benefit with simvastatin.
"I think we're pretty conclusive in showing that simvastatin doesn't have any effect on the lung itself," said Dr. Criner. "If you are giving statins with the intent of decreasing the COPD exacerbation rate, don't give them. We probably need to look at other therapies that are more potent."
The researchers also evaluated whether the participants should have been receiving statin therapy.
"The retrospective studies didn't do that," Dr. Criner explained. "We found that 10% of exclusions in our study were people who should have been on statin therapy but were never tested for that."
It is possible that many patients in those retrospective studies who weren't on statins should have been, he said. It is also possible that some of the events considered COPD exacerbations were the result of unrelated cardiovascular events.
The study did show that statin therapy is fairly safe in these patients. "We were concerned that this group might be more susceptible to side effects because they're frail, but it was safe and well tolerated," he added.
Simvastatin does absolutely nothing for exacerbation of COPD in the absence of coronary artery disease, said Paul Jones, MD, PhD, professor of respiratory medicine at St. George's University of London, United Kingdom.
However, the study does suggest that in other studies, some of the exacerbations of COPD triggered by cardiovascular disease were reduced with statins, he told Medscape Medical News.
A previous retrospective study of statins reported a beneficial effect in COPD (Am J Respir Crit Care Med. 187;2013:A6017). However, the prospective study by Dr. Criner's team puts those results in a new light.
The failure to reproduce retrospective studies is not uncommon in COPD, said Dr. Jones. "It's quite consistent: When they've been tested in a randomized controlled trial, with clear inclusion and exclusion criteria, there's no signal at all."
Strike 2: Acute Respiratory Distress Syndrome
Statins also struck out in a trial looking at the effectiveness of rosuvastatin in sepsis-associated acute respiratory distress syndrome (ARDS). It too was presented at the ATS meeting and published online simultaneously in the New England Journal of Medicine.
The 745 patients in the trial were randomized to receive either rosuvastatin or placebo. The primary outcome was in-hospital mortality; secondary outcomes included the number of ventilator-free days.
There were no significant differences in mortality or ventilator-free days between the 2 groups.
Table 2. Outcomes
| Outcome | Rosuvastatin | Placebo | P value |
| Mortality | 28.5% | 24.9% | 0.21 |
| Ventilator-free days | 15.1 | 15.1 | 0.96 |
This study was also stopped early by the data safety and monitoring board.
"Although both trials had negative results, they had to be done — not because statins were widely used for COPD or sepsis-associated ARDS, but because we needed to bridge the gap between information gleaned by deduction from observation (something we thought was working) and information gleaned from interventional experimentation (something we know works — or in this case, does not work)," write Jeffrey Drazen, MD, and Annetine Gelijns, PhD, in an editorial accompanying the 2 studies.
The COPD study was funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research. The ARDS study was funded by the National Heart, Lung, and Blood Institute and AstraZeneca. Dr. Criner and Dr. Jones have disclosed no relevant financial relationships.
American Thoracic Society (ATS) 2014 International Conference. Presented May 18, 2014.
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Cite this: Statins Don't Live Up to Hopes in Treatment of COPD or ARDS - Medscape - May 19, 2014.
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