Failing heart--medical aspects
Tolerability of carvedilol in patients with heart failure and concomitant chronic obstructive pulmonary disease or asthma

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Abstract

Background

A substantial proportion of the population with congestive heart failure (CHF) has concomitant airway disease. Little information exists on the tolerability of carvedilol in patients with chronic obstructive pulmonary disease (COPD). In this study, we assessed the tolerability and efficacy of carvedilol in patients with CHF and concomitant COPD or asthma.

Methods

Between 1996 and 2000, a total of 487 patients began receiving open-label carvedilol. Forty-three (9%) had COPD (n = 31) or asthma (n = 12). Spirometry supported clinical diagnosis in all, and full pulmonary function testing supported diagnosis in 71%. Sixty percent began carvedilol therapy in the hospital and underwent measurement of peak expiratory flow rates (PEFR) before and after dosing.

Results

In patients with COPD, mean forced expiratory volume in one second (FEV1) was 62% ± 13% predicted, reversibility was 4% ± 4% with bronchodilators, and FEV1/FVC was 62% ± 8%. Mean PEFR was 325 ± 115 liter/min before the dose and increased by 17% 2 hours after the carvedilol dose (p = 0.04). In patients with asthma, mean FEV1 was 80% ± 17% predicted, reversibility was 13% ± 7% , and FEV1/FVC was 74% ± 11%. Mean PEFR was 407 ± 161 liter/min before the dose with no significant change 2 hours after the dose. Carvedilol was introduced safely in 84% of patients with COPD, with only 1 patient withdrawn from therapy for wheezing. In contrast, only 50% of patients with asthma tolerated carvedilol. Survival at 2.5 years was 72%. In survivors, left ventricular end-diastolic diameter decreased from 76 ± 11 mm to 72 ± 14 mm (p = 0.01), left ventricular end-systolic diameter decreased from 65 ± 13 mm to 60 ± 15 mm (p = 0.01), and fractional shortening increased from 14% ± 7% to 17% ± 7% (p = 0.05) at 12 months.

Conclusions

Patients with CHF and COPD tolerated carvedilol well with no significant reversible airflow limitation, but patients with CHF and asthma tolerated carvedilol poorly. The effect of carvedilol on left ventricular dimensions and function in patients with concomitant airway diseases was similar to that seen in our general group of patients. Asthma remains a contraindication to β-blockade.

Section snippets

Patient population

From 1996 to 2000, a total of 487 patients began receiving open-label carvedilol for treatment of New York Heart Association (NYHA) functional Class I to Class IV systolic chronic heart failure. All patients attended a heart failure clinic at one institution and had received heart failure therapy for at least 3 months before beginning carvedilol therapy. The only exclusion criteria to attempting to introduce carvedilol were cardiogenic shock, intractable pulmonary and systemic edema, heart

Results

Of the 43 patients, 31 had COPD and 12 had asthma. The patients were predominantly men (88%) with moderately severe heart failure, as shown by the baseline demographics in Table I .

Lung function in heart failure

The interpretation of restrictive and obstructive defects observed with pulmonary function testing in patients with heart failure is difficult when concomitant airway disease is present.5, 6, 7 Reversible obstructive defects have been described in acute cardiac failure, whereas a restrictive defect with reduced DLCO is more typical of chronic congestive cardiac failure. The range of mechanisms proposed for the restrictive pattern includes respiratory muscle weakness, reduced lung volume caused

Conclusion

A large number of patients with heart failure and COPD can, in fact, tolerate carvedilol therapy and achieve substantial cardiac benefits from the treatment. The maximum dose of carvedilol achieved, tolerability, and improvements in cardiac function and survival were similar to those seen in our previously described patients who received open-label carvedilol for treatment of heart failure.8, 15 Despite the small number of patients in our study, asthma with significant reversibility (defined as

References (21)

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