Feb 062018

By Salynn Boyles, Contributing Writer, MedPage Today

Treatment with statins may be beneficial in terms of improving exercise tolerance, pulmonary function and quality-of-life among chronic obstructive pulmonary disease (COPD) patients with co-existing cardiovascular disease, increased systemic inflammation or hyperlipidemia.

That is the finding from meta-analysis of 10 randomized, controlled trials involving close to 1,500 patients, reported in the December issue of a society-published journal.

Use of statins was not associated with statistically significant differences in inflammatory markers, all-cause mortality and safety outcomes.

But subgroup analysis suggested improved clinical outcomes associated with statin use among patients enrolled in trials that included patients with cardiovascular disease (CVD), elevated baseline C-reactive protein, and high cholesterol levels.

"The current collective evidence suggests a role for statin therapy in several different aspects of COPD-specific outcomes," wrote researcher Wen Zhang of Xinqiao Hospital, Chongqing, China, and colleagues. "It also appears that patients with comorbid CVD and higher baseline lipids may have greater benefits including lung function benefits, whereas they had no effect in those with normal LDL-C levels."

Statins: Little Benefit for COPD in Pivotal Trial

The systematic review is one of several recent studies which examined the potential benefits of lipid-lowering drugs in COPD patients.

The randomized, controlled STATCOPE trial involving close to 900 patients, published in 2014, showed no benefits for daily simvastatin treatment for reducing exacerbation rates or time to first exacerbation in high-risk patients. But the trial excluded patients with CVD or strong risk factors for CVD.

STATCOPE investigator Robert M. Reed, MD, of the University of Maryland School of Medicine, Baltimore, told MedPage Today that the study findings did a lot to dampen enthusiasm about the use of statins in the COPD setting.

He added that the exclusion of patients with CVD or risk factors for CVD was seen as a significant limitation.

"The inflammation that exists in COPD also affects the blood vessels, and that is what statins treat," Reed said. "So one criticism at the time was that the patients included in the trial may have been those who were least likely to benefit from statins."

Reed said a strength of the newly published meta-analysis is that in addition to the STATCOPE cohort, the analysis included patients with CVD from other randomized trials.

The systematic review and meta-analysis included a total of 1,471 patients, including 728 randomized to the statin group and 743 randomized to the control group. Across the trials, the proportion of male patients and current smokers ranged from 52% to 100% and 0% to 81%,respectively.

Among the trials included in the meta-analysis, nine were either double- or triple-blind and the remaining trial was a single-blind design.

Among the main findings:

  • Five studies examined change in 6-minute walk distance, and the analysis found a significant benefit in this outcome associated with statin use: 6-minute walk distance was greater by 15.5 m (95% CI, 1.43 to 29.65; P=0.03).
  • Seven of the trials included FEV1 data. Statin use was associated with a slight, but not significantly greater, improvement in FEV1 % predicted (mean difference 3.2%; 95% CI -0.30% to 6.78%; P=0.07).
  • Six studies included data on inflammatory status as measured by CRP. A non-significant trend in CRP reduction was seen in patients receiving statins, with a moderate degree of statistical heterogeneity among the trials (I2=56.6%).
  • Three trials evaluated quality-of-life using St. George's Respiratory Questionnaire. Statin use was associated with a larger improvement in quality-of-life, compared to placebo (mean difference -8.9, 95% CI -15.0 to -2.32; P=0.008).
  • Subgroup analysis showed statin use to improve exercise tolerance in patients with COPD and CVD comorbidity, but this benefit was not seen in an analysis of studies excluding patients with CVD and those at high risk for developing CVD.
  • Four trials including a total of 1,054 patients reported all-cause mortality, with 29 deaths occurring among 518 patients in the treatment group and 31 deaths among 536 patients in the control groups. No statistically significant difference was seen between the treatment and control groups.

Statins for COPD? Important Questions Remain

"Unlike the results of observational studies, we showed no effects of statin therapy on mortality in COPD patients, but the patient cohorts in the RCTs were small and the study periods were short, so the long-term effects of statins on life expectancy of COPD population remained unclear," the researchers wrote.

In addition to the limited number of patients with CVD, study limitations cited by the researchers included the relatively small size of the pooled patient cohort, and inability to analyze important specific COPD outcomes, including acute exacerbations."

"The findings support routine cardiovascular risk assessment in the COPD population to identify patients who have a cardiovascular indication for statin treatment, since it might also bring direct benefits to the pulmonary system," the researchers wrote.

They added that the findings also justify a large randomized, clinical trial including patients with comorbid COPD, elevated systemic inflation and/or hyperlipidemia.

Reed said that while many questions remain about the use of statins in the COPD population, others have been answered.

"We have pretty good data telling us that statins are not going to make it less likely that a patient will have a COPD exacerbation," he said. "And there is no reason to believe that statins are harmful in COPD patients."

He added that there may be some off target benefits in patients who are not clear candidates for statin therapy.

Pulmonary specialist Byron Thomashow, MD, of Columbia University Medical Center, New York City, agreed that important questions remain about the use of statins in the COPD setting.

"The jury is still out," he told MedPage Today.

"Since COPD appears to be an independent risk factor for cardiovascular disease and since many with COPD die of cardiovascular disease, it would make sense that statins could have benefit, but that has yet to be clearly defined. The study adds further clues to possible roles, but too many questions still exist to have a clear answer."

This study was funded by the National Natural Science Foundation of the People's Republic of China.

The researchers declared no relevant relationships with industry related to this study.

Source Reference: Society journal

--From MedPage Today

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Meta-analysis: statins for COPD associated with better walk distance and quality of life