This narrative review defines cardiopulmonary risk as the risk of serious respiratory and/or cardiovascular events in patients with chronic obstructive pulmonary disease (COPD). |
Many people with COPD are at elevated cardiopulmonary risk, which may lead to early death. |
Current evidence supports proactive therapeutic intervention to prevent exacerbations, reduce the risk of cardiopulmonary events and thereby reduce mortality in patients with COPD. |
Reframing the management of COPD towards proactive cardiopulmonary risk reduction could transform the standard of care and, therefore, improve clinical outcomes. |
Introduction
Definition of Cardiopulmonary Risk
‘The risk of serious respiratory and/or cardiovascular events in patients with COPD. These include, but are not limited to, COPD exacerbations, myocardial infarction, stroke, heart failure decompensation, arrhythmia and death due to any of these events.’ |
Factors Elevating COPD-Associated Cardiopulmonary Risk
Mechanisms
Reducing COPD-Associated Cardiopulmonary Risk
Exacerbation Risk Reduction
Cardiovascular Risk Reduction with Inhaled Therapy
Mortality Risk Reduction
Drug | Study (duration) | Moderate to severe exacerbation rate | Cardiovascular effects | All-cause mortality rate |
---|---|---|---|---|
ICS monotherapy | ||||
Budesonide | EUROSCOP [66] (3 years) | NR | ICS vs placeboa HR 0.58 (95% CI 0.35, 0.98; p = 0.043)b | NR |
LAMA monotherapy | ||||
Tiotropium | UPLIFT [50] (4 years) | LAMA vs placebo RR 0.86 (95% CI 0.81, 0.91; p < 0.001) | NR | LAMA vs placebo HR 0.89 (95% CI 0.79, 1.02; p = 0.09) |
POET-COPD [51] (1 year) | LAMA vs LABA RR 0.89 (95% CI 0.83, 0.96; p = 0.002) | NR | LAMA vs placebo HR 0.81 (95% CI 0.58, 1.13; p = 0.21) | |
ICS/LABA dual therapy | ||||
Fluticasone propionate / salmeterol | TORCH [81] (3 years) | ICS/LABA vs placebo RR 0.75 (95% CI 0.69, 0.81; p < 0.001) | ICS/LABA vs placeboc 4% vs 5%d | ICS/LABA vs placebo HR 0.825 (95% CI 0.681, 1.002; p = 0.052) |
Fluticasone furoate / vilanterol | SUMMIT [69] (3 years)e | ICS/LABA vs placebof RR 0.71 (95% CI 0.65, 0.78; p < 0.0001)g | ICS/LABA vs placeboh HR 0.93 (95% CI 0.75, 1.14)i | ICS/LABA vs placebo HR 0.88 (95% CI 0.74, 1.04; p = 0.137) |
LAMA/LABA dual therapy | ||||
Indacaterol / glycopyrronium | FLAME [52] (1 year) | LAMA/LABA vs ICS/LABA RR 0.83 (95% CI 0.75, 0.91; p < 0.001) | NR | NR |
CLAIM [67] (6 weeks) | NR | LAMA/LABA vs placeboj 61.76 mL/m2 vs 56.53 mL/m2; LS means treatment difference 5.23 mL/m2 (95% CI 3.22, 7.25; p < 0.0001) | NR | |
ICS/LAMA/LABA fixed-dose combination triple therapy | ||||
Fluticasone furoate / umeclidinium / vilanterol | (1 year) | ICS/LAMA/LABA vs LAMA/LABA RR 0.75 (95% CI 0.70, 0.81; p < 0.001) [53] vs ICS/LABA RR 0.85 (95% CI 0.80, 0.90; p < 0.001) [53] | ICS/LAMA/LABA vs LAMA/LABAc 0.6% vs 1.0% [71]d,k | ICS/LAMA/LABA vs LAMA/LABA HR 0.72 (95% CI 0.53, 0.99; p = 0.042) [71]l |
FULFIL [56] (24 weeks) | ICS/LAMA/LABA vs ICS/LABA RR 0.65 (95% CI 0.49, 0.86; p = 0.002) | NR | NR | |
Budesonide / glycopyrrolate / formoterol fumarate | (1 year) | ICS/LAMA/LABA vs LAMA/LABA RR 0.76 (95% CI 0.69, 0.83; p < 0.001) [54] vs ICS/LABA RR 0.87 (95% CI 0.79, 0.95; p = 0.003) [54] | ICS/LAMA/LABA vs LAMA/LABAn 0.5% vs 1.4%; 1.4% vs 2.1%; 0.4% vs 0.8% [70]d | ICS/LAMA/LABA vs LAMA/LABA HR 0.51 (95% CI 0.33, 0.80; unadjusted p = 0.0035) [70]o |
KRONOS [57] (24 weeks) | ICS/LAMA/LABA vs LAMA/LABA RR 0.48 (95% CI 0.37, 0.64; p < 0.0001) | NR | NR | |
Beclometasone dipropionate / glycopyrronium / formoterol fumarate | TRILOGY [59] (1 year) | ICS/LAMA/LABA vs ICS/LABA RR 0.77 (95% CI 0.65, 0.92; p = 0.005) | All extrafine ICS-containing treatments vs ICS-free therapiesp HR 0.65 (95% CI 0.43, 0.97; p = 0.037) [72]q | All extrafine ICS-containing treatments vs ICS-free therapies HR 0.71 (95% CI 0.50, 1.02; p = 0.066) [72]q |
TRINITY [58] (1 year) | ICS/LAMA/LABA vs LAMA RR 0.80 (95% CI 0.69, 0.92; p = 0.0025) | |||
TRIBUTE [60] (1 year) | ICS/LAMA/LABA vs LAMA/LABA RR 0.848 (95% CI 0.723, 0.995; p = 0.043) |