Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD

Abstract

BACKGROUND Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial. METHODS We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second [FEV1] of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers. RESULTS A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (±SD) age of 62.2±8.4 years, an FEV1 that was 41.6±17.7% of the predicted value, and a smoking history of 50.6±27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36±1.61 exacerbations and 1.39±1.73 exacerbations, respectively (P = 0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval [CI], 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P = 0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P = 0.89). CONCLUSIONS Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.)

Interpretation of the evidence for the efficacy and safety of statin therapy

“…infections, [201][202][203] chronic obstructive lung disease, [204][205][206] and acute respiratory distress syndrome 207 ), but those claims have been reliably refuted by randomized trials of adequate size. [208][209][210][211][212] These findings reinforce concerns about basing inference about treatment effects on relatively small numbers of events in randomized trials or on observational studies irrespective of their size. 3,4,213,214 In summary, lowering LDL cholesterol with statin therapy has been shown to prevent both non-fatal and fatal major vascular events in a wide range of circumstances, and the absolute benefits depend chiefly on an individual's absolute risk of such events and on the magnitude of the LDL-reduction that is achieved (as well as the duration of treatment).…”

Comparison of Long Term Oxygen-Therapy (LTOT) and LTOT Combined with Sildenafil and Simvastatin in the Treatment of Severe Chronic Obstructive Pulmonary (COPD) with Hypoxia at Rest and Severe Pulmonary Arterial Hypertension

“…Sildenafil might decrease dyspnea by its effect on pulmonary arterial vasodilation via increasing cyclic guanosine monophosphate (cGMP) produced by nitric oxide (NO) [25,26]. Although the effect of simvastatin in severe COPD has been demonstrated previously [27], the combination of sildenafil and simvastatin in reducing dyspnea status in these patients has not been clarified. It might be due to the effect of this combined treatment on pulmonary arterial pressure (PAP).…”

Chronic Obstructive Pulmonary Disease: Lessons from the Important Treatment Trials

“…being the definition used in the Simvastatin Therapy for Moderate and Severe COPD (STATSCOPE) study 14 . Use of diary cards can, at least in part, ameliorate this effect but significantly increase the work involved for both subject and researcher.…”