Review ArticleBronchodilators in Heart Failure Patients With COPD: Is It Time for a Clinical Trial?
Section snippets
Factors Contributing to Worse Outcomes With Comorbid COPD and HF
Diagnostic difficulties and the overlapping signs and symptoms between HF and COPD contribute to worse outcomes in this patient population. Lung hyperinflation in COPD can hinder auscultation of rales or an S3, mask radiographic pulmonary edema, and impede acoustic windows on echocardiography, resulting in underestimation of the contribution of HF to the clinical presentation.2 Similarly, HF can reduce lung volumes and obscure the presence of airflow limitation on pulmonary function testing in
Bronchodilator Therapies
The guidelines for COPD management recommend medical therapy based on the degree of airflow obstruction (Fig. 1).32, 33 Treatment for mild obstruction (1-s forced expiratory volume [FEV1] ≥80% of predicted) includes short-acting bronchodilators, and moderate (FEV1 50%–80%) to severe (FEV1 <50%) obstruction warrants regular therapy with long-acting bronchodilators and consideration of inhaled corticosteroids and long-acting beta-agonists as combination therapy (Table 1).34, 35 Current guidelines
Bronchodilators in HF
The impact of inhaled bronchodilators on outcomes has never been prospectively evaluated in HF patients. Limited observational data exist regarding outcomes related to the use of bronchodilators in HF (Table 2). Because worse outcomes with bronchodilators in the studies may be attributed to confounding by indication or may reflect COPD severity rather than an adverse effect of therapy, the results should be viewed as exploratory. Two studies showed that in HF patients (including those with17
B2As
In this review we focus on the effects of B2As via the inhaled route, because data from a moderate-size randomized trial (n = 516) demonstrated increased mortality with an oral B2A in HF patients40 and current COPD clinical practice guidelines favor inhaled bronchodilators.32 The TORCH study investigated a large randomized sample of COPD patients treated with inhaled B2As with or without inhaled steroid compared with placebo.10 That study of 6,112 patients documented that the overall mortality,
Rationale for a Clinical Trial
Few of the observational studies and none of the RCTs of bronchodilators have adequately investigated their use in HF patients.36, 41 More recently, there has been a tendency to favor ACh over B2As in this population18; however, there are little data specifically in HF patients that demonstrate safety and efficacy of an ACh-based regimen. Recent studies excluded HF patients, were not designed to investigate CV events, lacked CV end point adjudication and strict intention-to-treat analysis, and
Proposed Trial
We propose a multicenter double-blind RCT of long-acting ACh therapy with or without long-acting B2A therapy in outpatients with stable HF and COPD. Given the significant heterogeneity of this population, there will be strict inclusion and exclusion criteria (Table 3) designed to focus the investigation on patients with significant systolic dysfunction (ie, beta-blocker requirement) and moderate-severe COPD (ie, bronchodilator requirement) as documented on pulmonary function tests (PFTs; FEV1
Conclusion
COPD is present in up to one-third of HF patients. These patients commonly receive bronchodilator therapies for which safety concerns have not been systematically evaluated. Overall, long-acting AChs have more reassuring cardiovascular safety profiles than B2As and may be the preferred first-line agents for COPD patients with comorbid HF, but these considerations need to be evaluated in a randomized trial before broad clinical application. We have provided the framework for a large-scale
Disclosures
None.
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2016, International Journal of CardiologyHypertensive heart disease and bronchodilators: Potential left ventricular outflow obstruction
2015, International Journal of CardiologyNoncardiac comorbidities in heart failure with reduced versus preserved ejection fraction
2014, Journal of the American College of CardiologyCitation Excerpt :Moreover, HF may result in pulmonary function changes and patient symptoms that mimic COPD. Because patients with preserved EF do not have the alternative diagnosis of low EF, they may be more likely to receive a COPD diagnosis as an explanation for dyspnea (33,34). Despite the potential for bias related to increased COPD diagnosis in HFpEF patients, the consistent observation of increased COPD prevalence in HFpEF patients suggests that concomitant pulmonary and cardiac dysfunction may be particularly important in the preserved EF group.
Multicentric study on the beta-blocker use and relation with exacerbations in COPD
2014, Respiratory MedicineCitation Excerpt :Interestingly enough, there is a decrease in the proportion of patients treated with “traditional” LABAs in the BB group, in part compensated by an increase in the use of ultra-LABA. This may show the fear to prescribe “traditional” LABA by those physicians more aware of cardiac disease management —those also more prone to use BB— since there is some evidence associating “traditional” LABA to increased mortality in both patients with CHF and with CAD [23–26]. The reduction in the use of “LABA” results in less inhaled corticosteroids use as well since “traditional” LABA were almost always prescribed in fixed-dose combinations in this cohort.
Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: An efficacy and safety analysis of SHIFT study
2013, International Journal of CardiologyCitation Excerpt :In addition, the frequent use of subguideline-recommended doses of beta-blockers in SHIFT, similar to the findings in all recent registries of HF patients [22,23], precluded a specific assessment of the importance of beta-blocker “underdosing” in COPD. As a corollary, the impact of bronchodilators in HF patients with COPD cannot be inferred from SHIFT data and will require specific well-designed studies [24]. Several studies, including a recent meta-analysis [13], indicate that the clinical effect of beta-blockade in HF is closely related to reduction in heart rate and not to drug dose, suggesting that the primary benefit-producing effect of these agents in HF derives from heart rate modulation.
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