From the Journals

Statins linked to lower death rates in COPD

Dr. Vera De Palo
Vera A. De Palo, MD, MBA, FCCP, comments: The interplay of multiple chronic diseases contributing to a patient’s medical history is a complex one. As the provider seeks to treat the whole patient, improvements in common endpoints may occur. The observations of the authors of this study are interesting. Further study could help better understand the effects of statins in COPD patients.



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.

The findings belie those of the recent Simvastatin in the Prevention of COPD Exacerbation (STATCOPE) trial, in which daily simvastatin (40 mg) did not affect exacerbation rates or time to first exacerbation in high-risk COPD patients, wrote Larry D. Lynd, PhD, a professor at the at the University of British Columbia, Vancouver, and his associates. Their study was observational, but the association between statin use and decreased mortality “persisted across several measures of statin exposure,” they wrote. “Our findings, in conjunction with previously reported evidence, suggest that there may be a specific subtype of COPD patients that may benefit from statin use.” The study appears in the September issue of CHEST (2017;152;486-93).

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. Inflammation-inhibiting therapy also reduced cardiovascular events and lung cancer in the recent CANTOS trial, which this issue covers on page 7.

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, 0.68-0.91; 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- 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.

Despite [its] limitations, the study results are intriguing and in line with findings from other retrospective cohorts, noted Or Kalchiem-Dekel, MD, and Robert M. Reed, MD, in an editorial published in CHEST (2017;152:456-7. doi: 10.1016/j.chest.2017.04.156).

How then can we reconcile the apparent benefits observed in retrospective studies with the lack of clinical effect seen in prospective trials, particularly the in the 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, said the editorialists, who are both at the pulmonary and critical care medicine division, University of Maryland, Baltimore.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 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, they said.

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. Neither editorialist had conflicts of interest.

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