Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study

Abstract

Several studies have shown that statins have beneficial effects in chronic obstructive pulmonary disease (COPD) regarding lung function decline, rates and severity of exacerbations, hospitalisation and need for mechanical ventilation.We performed a randomised double-blind placebo-controlled single-center trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for COPD criteria II-IV at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and main outcome parameter was time to first exacerbation.Overall 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days, log-rank test p<0.001. Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34–0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%), p=0.003. The annualised exacerbation rate was 1.45 per patient-year in the simvastatin group and 1.9 in the placebo group (IRR 0.77, 95% CI 0.60 to 0.99).We found no effect on quality of life, lung function, 6-minute walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29).In our single-center RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

The Influence of Prior Statin Use on the Prevalence and Exacerbation of Chronic Obstructive Pulmonary Disease in an Adult Population

“…This population-based case-control study showed that statin use decreased the probability of emergency room (ER) visits and hospitalizations due to COPD exacerbations among participants with COPD, which was consistent with the results of previous studies ( 10 – 12 , 28 – 31 ). The novelty of our study includes the demonstration of different anti-inflammatory effects of statins according to their tissue selectivity; lipophilic statins showed a more profound effect on the prevention of exacerbations than hydrophilic statins.…”

“…Population-based case-control studies demonstrated that statin use affects AEs in COPD patients requiring hospitalization (OR = 0.67∼0.70, and HR = 0.66) ( 29 – 31 , 34 ). A recent RCT by Schenk et al showed that the rate of exacerbations was 1.45 events (patient-years) in the simvastatin group and 1.9 events (patient-years) in the placebo group (incidence rate ratio = 0.77, 95% CI 0.60–0.99) ( 12 ). However, the STATCOPE trial showed that simvastatin did not influence exacerbation rates or the time to a first exacerbation in COPD patients (1.36 ± 1.61 AEs for simvastatin and 1.39 ± 1.73 AEs for controls, respectively, P = 0.54) ( 13 ).…”

“…Moreover, we analyzed the effect of statins on AEs according to the pharmacological class of the statin and found that lipophilic statins such as atorvastatin, simvastatin, fluvastatin, and pitavastatin have more potent preventive effects against AEs. Two RCTs chose simvastatin because it showed pleiotropic effects in in vitro studies and a maximal reduction in serum CRP levels at the usual dose (20–40 mg per day) without an increase in side effects ( 12 , 13 ). Network meta-analysis showed supporting evidence that fluvastatin and atorvastatin (lipophilic) had a higher cumulative probability of reducing CRP in COPD patients than rosuvastatin (hydrophilic) (97.7% for fluvastatin, 68.9% for atorvastatin, and 49.3% for rosuvastatin) ( 28 ).…”

“…Previous systematic reviews have reported that statins reduce the risk of mortality, hospitalization, and levels of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) in COPD patients ( 10 , 11 ). A recent randomized controlled trial (RCT) stated that one year of treatment with simvastatin at 40 mg per day decreased the risk of exacerbations ( 12 ). However, a well-known RCT, the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE), showed that simvastatin did not have any preventive effect on AEs in COPD ( 13 ).…”

Statin prescription in patients with chronic obstructive pulmonary disease and risk of exacerbations: a retrospective cohort study in the Clinical Practice Research Datalink

“…22 Recently published results from another small trial do however indicate some benefit of statin treatment on COPD exacerbation and mortality. 24 An explanation put forward by the authors for these results is that the study population was nearer 'real world' than in previous trials as it included patients with subclinical cardiovascular disease. CVD is strongly linked to COPD, 25 26 and so some hospital admissions for severe exacerbation may have been attributable to CVD.…”