CME Author: Zeena Nackerdien
Study Authors: Claire A. Lawson, Mamas A. Mamas, et al.
Target Audience and Goal Statement:
Cardiologists and pulmonologists
The goal was to understand a British retrospective database analysis designed to determine the associations between chronic obstructive pulmonary disease (COPD) medication intensity or stage of airflow limitation and the risk of hospitalization in patients with heart failure (HF).
COPD increases the risk of poor outcomes in patients with HF, but the effect of COPD severity is not known. The study authors posed the following questions:
- Can they identify the highest-risk HF patients with COPD?
- What lessons can be learned from record-based prognostic stratification to improve care for patients with HF?
Synopsis and Perspective:
Using the large Clinical Practice Research Datalink linked to Hospital Episode Statistics during 2002 and 2014, the researchers performed two nested case-control studies of HF patients, with and without COPD, to assess the associations between COPD medication intensity or stage of airflow limitation, and the risk of hospitalization or death in patients with HF.
The 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines defines COPD as “a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.”
Diseases affecting the structure and function of the heart, including HF, are collectively known as cardiovascular diseases (CVD). COPD and HF commonly coexist and share similar risk factors. COPD is an independent risk factor for death in patients with HF and, conversely, HF is among the leading causes of hospitalization and death for patients with COPD and worsens their prognosis.
While COPD increases the risk of poor outcomes in HF patients, the effect of COPD severity is not known. Both diseases in this study were diagnosed based on clinical assessment and routinely required further investigations, such as echocardiography in those diagnosed with HF. About 40% of patients that were also diagnosed with COPD received spirometry.
Using the U.K. Clinical Practice Research Datalink (CPRD), the researchers included all patients, ages ≥40, with a new HF diagnosis in their clinical record during 2002 and 2012. Eligible patients had at least 3 years of CPRD-approved clinical data prior to study entry.
Patients were followed up until the first of the following events: date of transfer out of practice; index outcome event; or Jan. 1, 2014 (end date of study). HF patients with COPD were compared to patients without COPD.
For the study, COPD was defined by a clinical code and at least one COPD-related medication based on GOLD guidelines. The median forced expiratory volume (FEV1) measurement time was 295 days prior to mortality matching and 247 days prior to admission matching. Patients with COPD with routinely recorded spirometry were stratified by four GOLD-recommended severity stages:
- Mild: FEV1 ≥80% predicted
- Moderate: ≥50% FEV1 but <80% predicted
- Severe: ≥30% FEV1 but <50% predicted
- Very severe: FEV1 <30% predicted
This nested case-control study of 50,114 patients with HF (median age 79; 46% women) showed that COPD (18,478 cases or 13.8%) was significantly associated with hospitalization (adjusted odds ratio 1.33, 95% CI, 1.26-1.39) and increased death (aOR 1.31, 95% CI 1.26-1.36). Results showing that these risks increased by more than a third in the presence of coexisting COPD was specific to patients receiving intense COPD medication regimens, such as triple inhaler therapy, prescribed oral corticosteroids, or oxygen therapy.
Spirometry is nearly ubiquitous in primary care and is used to diagnose airflow limitation indicative of COPD in the presence of post-bronchodilator FEV1/forced vital capacity (FVC) values <0.7 with "appropriate symptoms and significant exposure to noxious stimuli," according to the 2019 GOLD guidelines. Spirometry was restricted to more severe study participants with HF and COPD and, within this context, the risk of death increased alongside elevated airflow limitation:
- FEV1 ≥80%: AOR 1.63 (95% CI 1.42-1.87)
- FEV1 50%-79%: 1.69 (95% CI 1.56-1.83)
- FEV1 30%-49%: 2.21 (95% CI 2.01-2.42)
- FEV1 <30%: 2.93 (95% CI 2.49-3.43)
On the other hand, associations between hospitalization risk and FEV1 were similar among stages, ranging from FEV1 ≥80% (AOR 1.48, 95% CI 1.31-1.68) to FEV1 <30% (AOR 1.73, 95% CI 1.40-2.12).
Claire Lawson, PhD, of the University of Leicester in England, and colleagues, said the study was the largest to date to examine the impact of COPD severity on outcomes in patients with HF. They added that while there is some evidence that COPD severity is an independent risk factor for HF death and hospitalization, the research has been limited.
Study limitations include the possibility of HF misclassification, presence of undiagnosed COPD, measurement errors due to HF features that can mimic airflow obstruction characteristic of COPD, and possible misdiagnosis of COPD, especially in the absence of pulmonary function assessment (about half of the patients with HF and coexisting COPD did not have spirometry data during the study period).
Source Reference: JAMA Open Network, Dec. 14, 2018; DOI:10.1001/jamanetworkopen.2018.5489
Study Highlights: Explanation of Findings
In an accompanying editorial, Frans H. Rutten, MD, PhD and Berna Broekhuizen, MD, PhD, of the Netherlands’ Utrecht University Medical Center in the Netherlands, stated that prescribed COPD medication intensity and FEV1 levels provide the basis for targeting high-risk groups. The need for taking great care with short-acting inhaled β-mimetics was illustrated by the finding that short-acting inhaler only or monotherapy in patients with HF and without COPD was significantly linked to an approximately 30% higher risk of all-cause hospitalizations; however, one alternative explanation may be inadequate management of exacerbations of HF, they said.
“The finding that short-acting inhaled β-mimics may be deleterious in patients with HF is a crucial finding and in line with literature, and should urge clinicians to refrain from prescribing these drugs that are not obligatory in COPD, but instead use inhaled long-acting β-mimetics and muscarin antagonists,” Rutten and Broekhuizen wrote. “In addition, we need valid diagnoses of both COPD and HF, and notably the diagnosis in the presence of the other is a challenge, even when a patient receives noninvasive diagnostic tests available for such cases.”
Lawson’s group outlined the clinical implications of the findings. First, the results demonstrated a need to accurately identify and effectively manage comorbidities to improve the prognosis of patients with HF. They noted that one in seven patients with HF also had COPD, which carries a 30% elevated risk of hospitalization and death versus HF patients without COPD.
Second, differences in COPD-associated risk according to medication intensity could serve as a marker of disease progression in patients with HF. However, the investigators noted that newer GOLD guidelines focus on symptoms-based severity assessment and the net effect could be overtreatment with pulmonary inhaler therapies in patients with HF and COPD.
Third, the risk of mortality increased with more severe airflow limitation from GOLD stages 1 through 4, but no such association was observed for hospital studies. Further studies may be needed in a prevalent HF cohort to determine the prognostic value of FEV1 for hospital admissions.
Then, in keeping with higher mortality rates reported for women than men with comparable lung functions in a separate study, the investigators found that COPD in women with HF was associated with a 15% higher risk of death than in men. Possible reasons range from physiology to delayed diagnosis and suboptimal treatment responses. Taken together with other findings, an important group has been identified for treatment optimization, the investigators noted.
Finally, the authors commented that “some of the adverse outcomes in the HF population with COPD could be improved by targeting better diagnosis of both, optimizing drug treatment for both, and identifying patients with the greatest severity of HF and COPD for early aggressive treatment or close monitoring.”
Original story for MedPage Today by Salynn Boyles