Beta-blocker therapy may reduce exacerbations in moderate-to-severe COPD

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Beta-blocker therapy was linked to a lower incidence rate ratio of total exacerbations and severe exacerbations.
Beta-blocker therapy was linked to a lower incidence rate ratio of total exacerbations and severe exacerbations.

In patients with moderate to severe chronic obstructive pulmonary disease (COPD), cardiac geometry demonstrated by non-contrast computerized tomography (CT) scan can predict which patients will respond to β-blocker therapy with a reduction in exacerbation frequency, according to a new study published in the American Journal of Respiratory and Critical Care Medicine.1

Matthew J. Budoff, MD, of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, California, one of the study investigators, spoke with Pulmonology Advisor about the importance of the research. “We found that in patients with moderate-severe COPD those who had a high [right ventricle (RV)/left ventricle (LV)] ratio on CT [computed tomography] had a more substantial reduction in exacerbations and may selectively benefit from β-blocker therapy.”

Acute exacerbations are responsible for most of the disability and costs associated with COPD.2 However, current COPD medications, which affect inflammation and airflow, only have a modest reduction in exacerbation risk.2

Two studies3,4 have raised concern that β-blockers may worsen lung function in patients with COPD. However, a Cochrane Systematic Review of randomized trials does not support this.5 Also, multiple retrospective studies6-8 have shown that β-blockers may be associated with a reduction in the frequency of acute exacerbations. More recently, a 2016 study by Bhatt, et al showed that β-blockers were associated with a significant reduction in total and severe exacerbations in patients with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 2 to 4 COPD.2

Because COPD is associated with cardiac abnormalities, investigators in the current study hypothesized that patients with heterogeneous ventricular abnormalities might respond differently to β-blockers.

The researchers enrolled 3436 patients with COPD (GOLD stage 2-4) from the multicenter COPDGene cohort. Upon enrollment, medication data were recorded; participants were contacted prospectively every 3 to 6 months to record exacerbation frequency. Cardiac segmentation and measurement of ventricular volume and sphericity were performed via non-contrast CT scans using a statistical model. Statistical analysis was performed comparing adjusted rates of total and severe exacerbations in patients who were and were not taking β-blockers.

Data were drawn from 2902 patients over median 2.1-year follow-up (interquartile range [IQR]: 1.4-2.8). The researchers found that β-blocker use associated with a lower incidence rate ratio (IRR) of total exacerbations (IRR: 0.70; 95% CI, 0.57-0.86; P <.0001) and severe exacerbations (IRR: 0.58; 95% CI, 0.41-0.82; P =.002).

The patients more likely to respond to β-blockers included patients with a low left ventricle (LV) epicardial volume index (IRR: 0.40; P <.0001 for total exacerbations and IRR; 0.37; P =.001 for severe exacerbations), a high right ventricle (RV) epicardial volume index (IRR: 0.74; P =.040 for total exacerbations and IRR: 0.49; P =.005 for severe exacerbations) and an RV/LV ratio >median (IRR: 0.43; P <.0001 for total exacerbations and IRR: 0.31; P <.0001 for severe exacerbations).

In patients with a main pulmonary artery (PA)/ascending aorta (A) diameter >1.0, there was no reduction in exacerbation frequency (IRR: 0.78; 95% CI, 0.49-1.22; P =.271 for total number; IRR: 0.85; 95% CI, 0.47-1.52; P =.572 for severe exacerbations).

“Our finding of a lack of association between β-blocker use and exacerbation reduction in patients with PA/A>1 but a positive response in those [patients] with RV/LV>median suggests that the main beneficial effects are driven by the effects of β-blockers on the LV,” the researchers concluded. “Recent studies of β-blockers in idiopathic pulmonary hypertension, without LV involvement, suggest that they might be harmful.”

Study Limitations

  • Researchers were unable to estimate ventricular mass and end-diastolic or end-systolic volumes separately due to the type of CT scans used in the study

References

  1. Bhatt SP, Vegas-Sánchez-Ferrero G, Rahaghi FN, et al. Cardiac morphometry on computed tomography and exacerbation reduction with β-blocker therapy in COPD [published online April 25, 2017]. Am J Respir Crit Care Med. doi:10.1164/rccm.201702-0399LE
  2. Bhatt SP, Wells JM, Kinney GL, et al. β-Blockers are associated with a reduction in COPD exacerbations. Thorax. 2016;71(1):8-14. doi:10.1136/thoraxjnl-2015-207251
  3. van der Woude HJ, Zaagsma J, Postma DS, et al. Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers. Chest. 2005; 127(3):818-824. doi:10.1378/chest.127.3.818
  4. Egred M, Shaw S, Mohammad B, Waitt P, Rodrigues E. Under-use of beta-blockers in patients with ischaemic heart disease and concomitant chronic obstructive pulmonary disease. QJM. 2005;98(7):493-497. doi:10.1093/qjmed/hci080
  5. Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Db Syst Rev. 2005;(4):CD003566. doi:10.1002/14651858.CD003566.pub2
  6. Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med. 2010;170(1):880-887. doi:10.1001/archinternmed.2010.112
  7. Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011;342:d2549. doi:10.1136/bmj.d2549
  8. Farland MZ, Peters CJ, Williams JD, Bielak KM, Heidel RE, Ray SM. Beta-blocker use and incidence of chronic obstructive pulmonary disease exacerbations. Ann Pharmacother. 2013;47(5):651-656. doi:10.1345/aph.1R600
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