Although downgraded to third line therapy in current guidelines, theophylline is still widely used for treating obstructive airway disease. The appreciation of its anti-inflammatory actions at low serum concentrations has revived interest in this drug but its cardiac side effects are still a concern. N-terminal pro-brain natriuretic peptide (NT-proBNP) provides prognostic information and is increasingly recognized as a quantitative indicator of myocardial stress. This prospective study aimed to determine the effect of theophylline on NT-proBNP in outpatients, who were referred from primary care for pulmonologist evaluation of chronic dyspnea. We hypothesized that theophylline would increase NT-proBNP.
A total of 85 out of 730 patients reported taking theophylline for ≥ 4 weeks and had detectable serum concentrations. All patients underwent a comprehensive diagnostic work-up for both heart and lung disease. The effect of theophylline on NT-proBNP was evaluated by multiple regression analysis after adjustment for the type of heart disease (impaired left ventricular systolic function, atrial fibrillation, pulmonary hypertension, significant valvular disease, exercise-induced myocardial ischemia, or left ventricular hypertrophy) and important non-cardiac covariates (age, sex, BMI, and arterial hypertension).
The median theophylline serum concentration was 7.8 mg/l [interquartile range 4.6–11.5 mg/l]. After adjustment for the above-mentioned covariates, NT-proBNP was lower in patients on theophylline than in those not taking theophylline in the whole study group (n = 730; p = 0.03) and in those having both heart and lung disease (n = 147, p = 0.02). By contrast, theophylline had no effect on NT-proBNP in patients with lung disease and without heart disease (n = 434, p = 0.68).
Theophylline tends to reduce serum levels of NT-proBNP in patients with lung disease and coexistent cardiac disorders.
A low-dose theophylline therapy does not put an excess burden on the heart. The mechanism by which theophylline reduces NT-proBNP levels remains speculative. A theophylline-mediated decrease in ventricular filling pressures may play a role.
Siegfried Wieshammer, No Financial Disclosure Information; No Product/Research Disclosure Information