From the Journals

Statins linked to lower death rates in COPD

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Life after STATCOPE

Despite [its] limitations, the study results are intriguing and in line with findings from other retrospective cohorts. How then can we reconcile the apparent benefits observed in retrospective studies with the lack of clinical effect seen in prospective trials, particularly the Simvastatin in the Prevention of COPD Exacerbation (STATCOPE) study? Could it be that both negative and positive studies are “correct”? Prospective studies have thus far not been adequately powered for mortality as an endpoint. Perhaps the choice of the particular statin matters? While STATCOPE involved simvastatin, the majority of the cohort reported by Raymakers et al. received atorvastatin. [Or perhaps] the negative results of STATCOPE could be related to careful selection of study participants with a low burden of systemic inflammation.

This most recent study reinforces the idea that statins may play a beneficial role in COPD, but it isn’t clear which patients to target for therapy. It is unlikely that the findings by Raymakers et al. will reverse recent recommendations by the American College of Chest Physicians and Canadian Thoracic Society against the use of statins for the purpose of prevention of COPD exacerbations, but the suggestion of survival advantage related to statins certainly may breathe new life into an enthusiasm greatly tempered by STATCOPE.

Or Kalchiem-Dekel, MD, and Robert M. Reed, MD, are at the pulmonary and critical care medicine division, University of Maryland, Baltimore. Neither editorialist had conflicts of interest (Chest. 2017;152:456-7. doi: 10.1016/j.chest.2017.04.156).



Receiving a statin prescription within a year after diagnosis of chronic obstructive pulmonary disease was associated with a 21% decrease in the subsequent risk of all-cause mortality and a 45% drop in risk of pulmonary mortality, according to the results of a large retrospective administrative database study.

A notepad that says, "Diagnosis COPD" copyright designer491/Thinkstock
COPD affects about 12% of adults aged 30 years and older worldwide and is associated with increased risk of progressive cardiovascular disease and cardiovascular mortality. “Localized chronic inflammation of the airways has long been observed in COPD patients, but there is a growing understanding of systemic inflammation in a subset of patients,” the researchers noted. For example, studies have linked chronic low-level systemic inflammation or elevated C-reactive protein levels with increased risks of severe airway obstruction, other pulmonary outcomes, and adverse cardiovascular events. Such findings prompted experts to suggest that COPD progression results from systemic inflammation, not a “spill over” of pulmonary inflammation, and that statins might help slow or block this process. Although STATCOPE did not support this idea, several prior observational studies did.

To further explore the question, the researchers analyzed linked health databases from nearly 40,000 patients aged 50 years and older who had received at least three prescriptions for an anticholinergic or a short-acting beta agonist in 12 months some time between 1998 and 2007. The first prescription was considered the date of COPD “diagnosis.” The average age of the patients was 71 years; 55% were female.

A total of 7,775 patients (19.6%) who met this definition of incident COPD were prescribed a statin at least once during the subsequent year. These patients had a significantly reduced risk of subsequent all-cause mortality in univariate and multivariate analyses, with hazard ratios of 0.79 (95% confidence intervals, 0.68 to 0.91; P less than .002). Statins also showed a protective effect against pulmonary mortality, with univariate and multivariate hazard ratios of 0.52 (P = .01) and 0.55 (P = .03), respectively.

The protective effect of statins held up when the investigators narrowed the exposure period to 6 months after COPD diagnosis and when they expanded it to 18 months. Exposure to statins for 80% of the 1-year window after COPD diagnosis – a proxy for statin adherence – also led to a reduced risk of all-cause mortality, but the 95% confidence interval for the hazard ratio did not reach statistical significance (0.71 to 1.01; P = .06).

The most common prescription was for atorvastatin (49%), usually for 90 days (23%), 100 days (20%), or 30 days (15%), the researchers said. While the “possibility of the ‘healthy user’ or the ‘healthy adherer’ cannot be ignored,” they adjusted for other prescriptions, comorbidities, and income level, which should have helped eliminate this effect, they added. However, they lacked data on smoking and lung function assessments, both of which are “important confounders and contributors to mortality,” they acknowledged.

Canadian Institutes of Health Research supported the study. One coinvestigator disclosed consulting relationships with Teva, Pfizer, and Novartis. The others had no conflicts of interest.

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