Statins improve exercise capacity, lung function in certain COPD patients
Statins may have therapeutic potential in chronic obstructive pulmonary disease (COPD), improving exercise tolerance, lung function and health-related quality of life, especially in patients with comorbid cardiovascular disease (CVD), elevated systemic inflammation or hyperlipidaemia, according to a recent study.
“The findings support routine cardiovascular risk assessment in COPD population to identify patients who have a cardiovascular indication for statin treatment, since it might also bring direct benefits to pulmonary system,” according to a team of academic researchers from China and United Kingdom.
The team performed a systematic review and meta-analysis of 10 randomized controlled trials evaluating the effects of statins vs placebo in COPD populations. The primary outcomes investigated were exercise tolerance (assessed by 6-minute walk distance) and lung function (assessed by forced expiratory volume in 1 second [FEV1] % of predicted value, FEV1 predicted; and a ratio of FEV1 to forced vital capacity, FEV1/FVC).
Pooled data revealed that compared with placebo, statin treatment significantly improved 6-minute walk distance by 15.5 m (95 percent CI, 1.43 to 29.65; p=0.03) and FEV1/FVC by 2.7 percent (0.05 to –5.25; p=0.05). The lipid-lowering drug was associated with only a numerical increase in FEV1 predicted (mean difference [MD], 3.2 percent; –0.30 to 6.78; p=0.07). [Chest 2017;doi:10.1016/j.chest.2017.08.015]
Among other outcomes investigated, only quality of life (measured by St. George’s Respiratory Questionnaire score) significantly differed between statin and placebo, in favour of the former (MD, –8.9; –150 to –2.32; p=0.008). Results for inflammatory markers (C-reactive protein, median neutrophil percentage in induced sputum), all-cause mortality and safety outcomes were comparable between the two treatment arms.
A subgroup analysis demonstrated improvements in clinical outcomes with statin vs placebo among patients with overt cardiovascular disease (6-minute walk distance: MD, 19.1 m; p=0.01; FEV1 predicted: MD, 3.75 percent; p=0.06; FEV1/FVC: MD, 2.74 percent=0.08), elevated baseline C-reactive protein (FEV1 predicted: MD, 4.41 percent; p=0.08; FEV1/FVC: MD, 5 percent; p=0.01) or high cholesterol levels (FEV1 predicted: MD, 3.82 percent; p=0.08; FEV1/FVC: MD, 3.61 percent; p=0.01).
“There was no obvious evidence for publication bias, as detected by the Begg’s and the Egger’s tests,” researchers said, adding that the results were robust in a sensitivity analysis restricted to trials that only enrolled stable COPD patients or statin-naïve patients, or with longer observational period (>3 months).
The total study population consisted of 1,471 COPD patients, among whom 728 were randomized to the statin arm and 743 to the placebo arm. Mean age varied between 49 and 72 years, while the proportion of males and current smokers ranged from 52 to 100 percent and 0 to 81 percent, respectively. Study duration was between 1 and 12 months, with a mean follow-up of 4.4 months.
“Unexpectedly, we found that statins appear to possess an ability to improve lung function in patients with COPD, which implies a direct benefit on statins on the pulmonary system,” researchers noted.
“Our data suggest that since statins may downregulate inflammation only in patients with concomitant CVD or hyperlipidaemia, the inclusion of patients without these characteristics in studies may mask possible treatment effects,” leading to the hypothesis that the underlying mechanism of beneficial effects in COPD patients could be a result of inhibition of systemic inflammation by statins, researchers added.
Despite the potential benefits of statins on lung function, “a diagnosis of COPD is not, of itself, an indication for routine use of statins. Equally, COPD is not a contraindication to statin treatment, so patients with COPD should be evaluated comprehensively for CVD and cardiovascular risks, in order to identify those warranting statin therapy,” they said.