May 18th, 2014
Statins Disappoint In COPD And ARDS
Two NHLBI studies have failed to find any benefit for statin therapy in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Previous observational studies had raised the possibility that statins, perhaps due to their anti-inflammatory effects, might improve outcomes in people with these serious diseases. But both trials were stopped early by their data and safety monitoring boards for futility. The results of the trials were presented at the annual meeting of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.
STATCOPE (Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations) randomized 885 patients with COPD to either simvastatin or placebo; patients taking or requiring statins were excluded. After 641 days of follow-up, there was no significant difference in the rate of COPD exacerbations or in the time to first exacerbation, the primary endpoint of the study.
There were also no differences in mortality, the rate of nonfatal serious adverse events, quality of life, or lung function. As expected, LDL levels were lower in the simvastatin group.
In a trial performed by the NHLBI’s ARDS Clinical Trials Network, 745 patients (out of a planned 1,000 patients) with sepsis-associated ARDS were randomized to either rosuvastatin or placebo. There was no significant difference in in-hospital mortality (28.5% in the rosuvastatin group vs. 24.9% in the placebo group, p=0.21). There was also no difference in the number of ventilator-free days.
However, in the first two weeks, patients on rosuvastatin had small but significant reductions in the number of days free of renal failure (10.1 + 5.3 vs.11.0 + 4.7, p =0.01) or hepatic failure (10.8 + 5.0 vs. 11.8 + 4.3, p =0.003). Rosuvastatin-treated patients also had higher levels of, and more adverse events relating to, aspartate aminotransferase, but it was unclear if these findings were clinically significant.
Although the trials were negative, they needed to be performed, write Jeffrey Drazen, Editor-in-Chief of the New England Journal of Medicine, and Annetine Gelijns in an accompanying editorial. “We needed to bridge the gap between information gleaned by deduction from observation…and something gleaned from interventional experimentation… It would have been a big mistake to accept the findings without a test… Had we accepted the observational data at face value, we might have spent the cost of the trials many times over in useless treatments before recognizing our errors. That raises a hard question: With the advent of big data, which observational associations should we test in rigorous trials?”