Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study

Abstract

While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min(-1)·m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients.

GDMT for heart failure and the clinician's conundrum

“…Adverse effects of beta blockers have also been reported in patients of heart failure with certain co‐morbid conditions. Bisoprolol has been reported to reduce cardiac output and 6 minute walk distance in patients with right ventricular dysfunction due to pulmonary hypertension, while Metoprolol succinate decreased cardiac index and increased NT‐pro BNP in patients with mild to moderate aortic stenosis even when LVEF was normal . Effectiveness of beta blockers in patients of heart failure with these common co‐morbidities have not been discussed in the guidelines, and their use appears mere extrapolation of the data of the trials.…”

Isolated heart model demonstrates evidence of contractile and diastolic dysfunction in right ventricles from rats with sugen/hypoxia-induced pulmonary hypertension

“…; Van Campen et al. ). This emphasizes that paradigms in LV research cannot be extrapolated to the RV and that specific studies of the RV are necessary.…”

The adrenergic nervous system as a therapeutic target in pulmonary arterial hypertension: a cautionary tale

“…The study by VAN CAMPEN et al [6] suffers from a numbers of limitations. 1) The choice of bisoprolol, a selective β 1 antagonist and potent antihypertensive agent, is questionable, and the results do not preclude a therapeutic benefit using other β-adrenergic agents with more complex actions on other receptors.…”

“…Nebivolol, a β 1 antagonist and β 2-3 agonist, inhibits proliferation of pulmonary vascular cells and produces endothelial and nitric oxide-dependent relaxation of pulmonary artery rings [3]; both nebivolol and pulmonary artery sympathetic denervation (PADN) attenuate vascular remodelling in monocrotaline-treated rats [3,4], and single-centre preliminary results of PADN in PAH patients are of considerable interest [5]. In this issue of the European Respiratory Journal, VAN CAMPEN et al [6] report the results of their single-centre study of the effects of β-adrenergic blockade in patients with PAH. Their results reinforce the notion that the pulmonary and systemic circulations and their respective ventricles behave very differently both in the pathogenesis of disease states and in response to targeted therapies.…”

“…Their results reinforce the notion that the pulmonary and systemic circulations and their respective ventricles behave very differently both in the pathogenesis of disease states and in response to targeted therapies. Using a cross-over design, VAN CAMPEN et al [6] evaluated 17 PAH subjects treated with bisoprolol. Bisoprolol produced no improvement in right ventricular ejection fraction measured by magnetic resonance imaging, but did result in a statistically (and clinically) significant decrease in both heart rate and cardiac index, and a trend toward reducing exercise capacity.…”