A December 2018 study, a retrospective analysis, looked at the relationship between heart failure and chronic obstructive pulmonary disease (COPD). In addition to investigating whether the two combined diseases raised the risk of earlier death, the British study also examined whether there is an association for all patients diagnosed with COPD (regardless of severity) or only when COPD is advanced and occurs with heart disease. In England, which has centralized government-regulated healthcare, the data linked to hospitals admission statistics was easy to access and then analyze.
COPD, heart failure, and mortality
Both conditions individually have been associated with hospitalization risk, so it would not surprise anyone that having both conditions can increase risk of death incrementally. The focus of the study was to see if the findings were related to COPD severity. Additionally, the researchers wanted to evaluate the direct impact of COPD treatments on mortality since drugs used to treat each condition have their own risk profile.
Hospitalization records that covered 2002 to 2012 were analyzed, with inclusion criteria set by the researchers. The COPD patients were stratified according to severity as defined by the GOLD guidelines.
The sample of patients included over 50,000 patients with heart failure. Of those,18,000 cases also had a diagnosis of COPD. That group with both conditions showed an increased risk of both hospitalizations and death. There was a unique association of earlier death among those who were receiving the most intense therapies - either in the form of triple-inhaler therapy or systemic corticosteroids.
The researchers were left to further assess - Was it the association with the more severe forms of COPD that are responsible for the worst outcomes (more hospitalizations and earlier death), or is it the intensity of the therapy necessary to treat the severe forms of COPD that resulted in increased cardiovascular risk and premature mortality?
Risks of bronchodilators
The concern that long-acting bronchodilator inhalers carry the risk of worsening cardiovascular events is not new. The FDA issued a black box warning when the combination of inhaled corticosteroids and long-acting bronchodilators came out on the market. The study designed to get FDA approval for use of this combo drug in asthma showed that there was increased mortality in those who took the medication compared to those who took a placebo.
When new combinations of inhaled corticosteroids and bronchodilators (intensive therapy) were used in the treatment of COPD, studies showed that there was an increase in the risk of developing pneumonia.
To further understand “intensive therapy” it’s important to highlight the more recent treatments available, also known as triple therapy. What is triple therapy? There are three types of drugs that are delivered through newer inhalers used to treat respiratory diseases:
- Inhaled corticosteroids (ICS) are the recommended first line of treatment for asthma
- Long acting bronchodilators (LABA) are the long-acting forms of the presently available rescue inhalers. They usually work by stimulating the adrenergic system which may explain the increase rate of the fast heart rate and also have the potential to cause cardiovascular complications
- Long-acting muscarinic agents (LAMA) act on the cholinergic system. This system works opposite to the adrenergic system in the body, causing airway spasms in the respiratory tract. These agents work to inhibit the cholinergic system.
The conventional thought process is to use the combination of ICS/LABA for asthma (adhering to the warning about the use of LABA as required by the FDA) and to use the combination of LABA/LAMA to treat COPD to target the cholinergic system, while being wary of the increased risk of pneumonia.
Treating with triple therapy
Many physicians, facing the frustration of dealing with severe disease and poor response in the treatment of COPD, have recently been using all three forms of therapy – triple therapy - with a variety of combinations of different inhalers. Trelegy is a newer triple therapy inhaler that finalized the term “triple therapy.”
A November 2018 study published in the British Medical Journal looked at the safety of triple therapy in one device with a meta-analysis of 21 studies. This study showed that there was a significant decrease in the number of exacerbations of COPD which is a predictor of worsening of disease. There was improvement in the perception of quality of life (by the patients). No clear effect on mortality was noted with the triple therapy approach, however, rate of pneumonia was still higher with triple therapy
Other COPD features affect risk
Another study looked at a different angle in trying to explore elevated mortality risk when comparing COPD patients with and without heart disease. This study selected the outcome of individuals admitted with myocardial infarction (heart attack) as the variable. It seemed that individuals with COPD were less likely to receive early “intervention,” in the form of cardiac catheterization. Earlier intervention and treatment might have resulted in better coronary health, and limited heart damage. One explanation for this missed intervention may be fear of pulmonary complications resulting from the treatment. It has been suggested that among COPD patients, risk of death is often underestimated, and this may allow heart disease complications to occur.
Then there’s the issue of common behavior patterns that encourage “complications.” The main one is smoking, a direct cause of COPD. Smoking induces inflammation in more areas of the body than just the airways. Inflammatory lipoproteins can enter the vascular endothelium, making it more permeable. This allows clot formation and can lead to complete blockage of the coronaries and ultimately fatal events. This may be another special contribution in which COPD adds to the risk of death from cardiovascular disease.
Congestive heart failure and heart attacks are conditions with high mortality rates. If you then add COPD as another condition in these patients, the research suggests that for several reasons, earlier mortality risk is increased.
See more helpful articles:
Is It COPD or Another Diagnosis?
Why Do COPD Inhalers Cost So Much?
An Apple a Day May Keep COPD Away