Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM‐HF

Abstract

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor Blocker–Neprilysin Inhibitor With Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non‐COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P <0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P <0.001) and Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (73 versus 81; P <0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta‐blockade (87% versus 94%; P <0.001) and diuretics (85% versus 80%; P <0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13–1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05–1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94–1.30), or all‐cause mortality (HR, 1.14; 95% CI, 0.99–1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05–1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29–1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM‐HF, COPD was associated with lower use of beta‐blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high‐risk subgroup. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01035255.

Impact of Chronic Obstructive Pulmonary Disease in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PARAGON‐HF

“…Patients with COPD were less likely to be treated with a beta blocker and had more severe functional limitation and impairment of quality of life than participants without COPD. While each of these findings are similar to those reported in patients with HFrEF with COPD, 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 there were also differences. Higher levels of NT‐proBNP have been reported in patients with HFrEF with COPD, 19 , 21 , 24 , 28 , 29 compared with patients with HFrEF without COPD.…”

“…While each of these findings are similar to those reported in patients with HFrEF with COPD, 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 there were also differences. Higher levels of NT‐proBNP have been reported in patients with HFrEF with COPD, 19 , 21 , 24 , 28 , 29 compared with patients with HFrEF without COPD. AF was more frequent in patients with HFrEF with COPD, compared with those without.…”

“…AF was more frequent in patients with HFrEF with COPD, compared with those without. 19 , 21 , 25 , 28 Although not reported in the HFrEF studies, in PARAGON‐HF use of oral nitrates was more common in patients with COPD than without COPD. The reason is not clear but may reflect treatment for angina (given the greater prevalence of coronary heart disease and lower use of beta blockers in patients with COPD) or in the belief that nitrates might be efficacious in heart failure (given the greater symptom severity and functional limitation in patients with COPD).…”

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

“…Nevertheless, the often-unjustified rejection of BB use is a common attitude in clinical practice. The results obtained in this study were in agreement with others that confirmed the underuse of BBs in patients affected by HF and concomitant COPD compared to patients without COPD ( 10 , 53 , 68 ); these data were also relevant at hospital discharge with an increased gap of up to 15% in disfavor of COPD vs. patients with HF alone ( 69 , 70 ). The limited prescription of BBs in this population is related to the onset of adverse respiratory effects mediated by β2-adrenoceptors blockade in the airways ( 71 , 72 ).…”

Optimal Management of Heart Failure and Chronic Obstructive Pulmonary Disease: Clinical Challenges

“…Using a non-standard definition (either self-reported by the patient or based on physician assessment, COPD treatment, or from review of the medical notes) the prevalence ranges between 10 and 25% ( Table 1 ). 20–28 Using spirometry to define the presence of COPD, the prevalence is higher and ranges between 25 and 50% ( Table 2 ). 29–33 The reasons for this discrepancy is unclear, but it may be due to undiagnosed COPD in patients with HF: the patient is breathless and the clinician has objective evidence of cardiac dysfunction (raised natriuretic peptide levels and/or reduced left ventricular ejection fraction (LVEF)), another potential cause of the symptoms may go overlooked.…”