The stats are in: an update on statin use in COPD

Figures & data

Table 1 Summary of statins in COPD retrospective trials and epidemiologic surveys

Trial	Study design	Patient characteristics	Outcomes
Bando et al^Citation29	Cross-sectional study	All Japanese outpatients >40 years old who regularly visited a participating primary health care facility n=853	Airflow limitation prevalence 2.25% in statin users vs 10.5% in non-users (P=0.01) Adjusted OR 0.28 (95% CI 0.06–1.28; P=0.101)
Lawes et al^Citation30	Population-based cohort	Patients 50–80 years old with hospitalization for COPD in New Zealand n=1,687 patients; 596 in statin group and 1,091 in non-statin group	242 deaths (40.6%) in statin users vs 429 (39.3%) in non-users Adjusted HR 0.69, (95% CI 0.58–0.84)
Sheng et al^Citation31	Population-based cohort	Patients with a diagnosis of COPD in Scotland Primary cardiovascular prevention cohort =1,274 patients; 617 in statin group and 657 in statin-unexposed group. Secondary cardiovascular prevention cohort =443 patients; 292 in the statin group and 151 in the statin-unexposed group	39% reduction in all-cause mortality in primary prevention statin users HR 0.61 (95% CI 0.43–0.85) 42% reduction in all-cause mortality in secondary prevention statin users HR 0.58 (95% CI 0.43–0.85)
Wang et al^Citation32	Retrospective nested case-control	All patients aged >45 years with two or more COPD-related outpatient visits that involved at least two COPD medications 14,316 patients resulting in 1,584 cases of hospitalization for ECOPD and 5,950 matched controls	Any use of statins is associated with a 30% reduction in exacerbations OR 0.70 (95% CI 0.56–0.88; P<0.05)
Ho et al^Citation33	Retrospective, population-based cohort	All patients who had been hospitalized for COPD exacerbations based on ICD-9 codes for COPD or pneumonia with secondary diagnosis of COPD n=4,204; 288 taking statins at enrollment	1 year mortality with statin use HR 0.33 (95% CI 0.47–0.91; P=0.013)
Ingebrigtsen et al^Citation34	Nested case-control	5,794 patients >40 years old diagnosed with COPD per GOLD criteria and a CRP measurement 530 cases with exacerbations matched to 1,016 controls	Statin use associated with reduced OR of exacerbation on univariate screen OR 0.68 (95% CI 0.51–0.91; P=0.01); multivariate logistic regression demonstrated OR 0.67 (95% CI 0.48–0.92; P=0.01); in the subgroup with the most severe COPD and no cardiovascular comorbidity, there was no difference; statin use also was associated with decreased CRP OR 0.69 (95% CI 0.56–0.85; P<0.001) and CRP was associated with increased risk of ECOPD HR 1.62 (95% CI 1.35–1.94; P<0.001)

Abbreviations: ECOPD, exacerbations of COPD; GOLD, Global Initiative for Chronic Obstructive Lung Disease; OR, odds ratio; HR, hazard ratio; CI, confidence interval; ICD-9, International Classification of Diseases, Ninth Revision; CRP, C-reactive protein.

Table 2 Summary of statins in COPD prospective and randomized clinical trials

Trial	Study design	Patient characteristics	Comparison	Outcomes
Bartziokas et al^Citation35	Prospective observational	All consecutive patients admitted to either of two tertiary hospitals with diagnosis of COPD exacerbation according to GOLD definition. All current or former smokers with 20 pack year history and previous diagnosis of COPD	Statin use vs non-use	No difference in 30-day or 1-year mortality
Huang et al^Citation36	Prospective population-based cohort	6,252 newly diagnosed COPD patients receiving statins for HLD, matched to 12,469 newly diagnosed COPD patients not taking statins	Statin use vs non-use	508 (8.1%) statin users were hospitalized compared to 1,324 (10.6%) non-users HR 0.66 (95% CI 0.60–0.74, P<0.001)
Lahousse et al^Citation37	Prospective NCC	Patients >55 years, diagnosed with COPD, CRP at baseline, at least 3 months of medication history, at least 2 years of follow-up between incident COPD and death 7,983 patients resulting in 363 cases matched to 2,345 controls	Statin use vs non-use	Statin use >2 years was associated with a 39% reduced risk of all cause death (95% CI, 0.38–0.99, P=0.045). When stratified by CRP, risk reduction increased to 78% (95% CI, 0.06–0.74, P=0.015) in those with CRP >3 mg/L
Criner et al^Citation38 STATCOPE	R, PC, P	40–80 years old with moderate-severe COPD defined by GOLD guidelines; current or former smoker with 10 pack year history; one of the following within 1 year of enrollment: supplemental O2, systemic steroids, antibiotics, ED visit or hospitalization for exacerbation n=885 patients; 433 in simvastatin arm, 452 in placebo arm	Simvastatin 40 mg vs placebo	No difference in exacerbation rates or time to exacerbation; trial stopped early for futility
Neukamm et al^Citation39 (2014) RODEO	R, PC, DB, P	Patients with COPD without a clear indication for statin therapy referred to two pulmonary outpatient clinics in Norway N=99; 49 in rosuvastatin group and 50 in placebo group	Rosuvastatin 10 mg vs placebo	No significant difference in change in vascular function (RHI 2.54 vs 2.51, P=0.292) or change in pulmonary function (FEV1, 1.35 L vs 1.45 L, P=0.462; FEV1/FVC, 47.3% vs 47.9%, P=0.292); improvement in inflammatory markers was seen in rosuvastatin group (CRP −20% vs 11%, P=0.017; IL-6 8% vs 30%, P=0.028)

Abbreviations: DB, double blind; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HLD, hyperlipidemia; NCC, nested case-control; P, parallel; PC, placebo controlled; R, randomized; RHI, reactive hyperemia index; ED, emergency department; HR, hazard ratio; CI, confidence interval; CRP, C-reactive protein.

BandoMMiyazawaTShinoharaHOwadaTTerakadoMSugiyamaYAn epidemiological study of the effects of statin use on airflow limitation in patients with chronic obstructive pulmonary diseaseRespirology201217349349822142478

 PubMed Web of Science ®Google Scholar

LawesCThornleySYoungRStatin use in COPD patients is associated with a reduction in mortality: a national cohort studyPrim Care Respir J2012211354022218819

 PubMedGoogle Scholar

ShengXMurphyMMacDonaldTEffect of statins on total cholesterol concentrations, cardiovascular morbidity, and all-cause mortality in chronic obstructive pulmonary disease: a population-based cohort studyClin Ther201234237438422244052

 PubMed Web of Science ®Google Scholar

WangMLoYTsaiCStatin use and risk of COPD exacerbation requiring hospitalizationAm J Med2013126759860623684060

 PubMed Web of Science ®Google Scholar

HoTWTsaiYJRuanSYIn-hospital and one-year mortality and their predictors in patients hospitalized for first-ever chronic obstructive pulmonary disease exacerbations: a nationwide population-based studyPLoS One2014912e11486625490399

 PubMed Web of Science ®Google Scholar

IngebrigtsenTMarottJNordestgaardBLangePHallasJVestboJStatin use and exacerbations in individuals with chronic obstructive pulmonary diseaseThorax2015701334025349333

 PubMed Web of Science ®Google Scholar

BartziokasKPapaioannouAMinasMStatins and outcome after hospitalization for COPD exacerbation: a prospective studyPulm Pharmacol Ther201124562563121729761

 PubMed Web of Science ®Google Scholar

HuangCCChanWLChenYCStatin use and hospitalization in patients with chronic obstructive pulmonary disease: a nationwide population based cohort study in TaiwanClin Ther201133101365137021962452

 PubMed Web of Science ®Google Scholar

LahousseLLothDJoosGStatins, systemic inflammation and risk of death in COPD: The Rotterdam studyPulm Pharmacol Ther201326221221723142156

 PubMed Web of Science ®Google Scholar

CrinerGConnettJAaronSDSimvastatin for the prevention of exacerbations in moderate to severe COPDN Engl J Med2014370232201221024836125

 PubMed Web of Science ®Google Scholar

NeukammAHoisethAEinvikGRosuvastatin treatment in stable chronic obstructive pulmonary disease (RODEO): a randomized controlled trialJ Intern Med20152781596725495178

 PubMed Web of Science ®Google Scholar