Beta blocker for patients with pulmonary arterial hypertension: A single center experience

Moretti, Claudio; Marra, Walter Grosso; D’Ascenzo, Fabrizio; Omedè, Pierluigi; Cannillo, Margherita; Libertucci, Daniela; Fusaro, Enrico; Meynet, Ilaria; Giordana, Francesca; Salera, Davide; Annone, Umberto; Chen, S.L.; Marra, Sebastiano; Gaïta, Fiorenzo

doi:10.1016/j.ijcard.2015.02.033

Cited by 13 publications

(13 citation statements)

References 19 publications

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“…The authors are to be commended for providing unique long-term follow-up data. The overall findings are consistent with other retrospective reports [25][26][27], but are in contrast to earlier case series [5]. This may be explained by the difference in patient population ( portopulmonary hypertension versus idiopathic PAH or PAH secondary to connective tissue disease) and the more frequent use of third generation β-blockers ( propranolol versus metropolol/carvedilol).…”

supporting

confidence: 89%

β-blockers in pulmonary arterial hypertension: evolving concepts of right heart failure

Man

Handoko

2015

Eur Respir J

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@ERSpublications Beta-blockers can be used safely by some PAH patients with comorbidities such as arrhythmias or hypertension http://ow.ly/P2JHgCurrent guidelines advise against the use of β-blockers in pulmonary arterial hypertension (PAH) to avoid systemic hypotension [1]. In addition, PAH patients have a fixed stroke volume, and are therefore highly dependent on heart rate to increase their cardiac output [2][3][4]. Indeed, PROVENCHER et al. [5] showed that withdrawal of β-blockers significantly improved exercise capacity in portopulmonary hypertension. PEACOCK and ROSS [6] described another case of portopulmonary hypertension, in which the use of a β-blocker to treat a supraventricular tachycardia in an already haemodynamically unstable patient was nearly fatal.Interestingly, patients with left heart failure also have a relatively fixed stroke volume [3,7]. However, in this case, β-blocker therapy (together with angiotensin-converting enzyme (ACE) inhibition) is considered the cornerstone of treatment [8]. How can we explain this discrepancy? PACKER [9] elegantly described the change in perspective on heart failure over the past 50 years. Until the 1960s, heart failure was solely regarded as an oedematous disorder, and the use of diuretics was central in the treatment. In the 1980s this view was extended with the cardiocirculatory model, in which heart failure was also viewed as a haemodynamic disorder. This led to the use of peripheral vasodilators and the development of positive inotropic agents. Although these agents effectively reduced symptoms, later it was consistently demonstrated that they increased mortality. Therefore, the conceptual view was adjusted again in the 1990s, and nowadays heart failure is also considered a neurohormonal disorder. This is the basis for the treatment with β-blockers and ACE inhibitors.We see a similar pattern emerging when looking at PAH-induced right heart failure, where more and more evidence is accumulating that might shift our conceptual framework from a solely haemodynamic to also a neurohormonal perspective. We have previously summarised the pathophysiological relevance of the neurohormonal axis in PAH [10,11]. In short, in PAH patients, sympathetic nervous system activity is increased and correlates with prognosis [12][13][14][15][16][17]. In addition, local changes in β-adrenergic receptor signalling of the right ventricular myocardium of PAH patients have been demonstrated [18][19][20]. Furthermore, in experimental PAH-models, β-blocker therapy reversed cardiac remodelling and improved outcome [21][22][23].Whereas it is much too early to advocate β-blockers treatment to reverse right heart failure in patients, signals are emerging that the dangers of β-blockers in PAH patients are much smaller than previously thought. In this issue of the European Respiratory Journal, BANDYOPADHYAY et al. [24] describe the outcomes of β-blocker use in the largest PAH cohort thus far. Most patients received β-blockers for treatment of arrhythmias, presumed congestive cardiac failu...

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confidence: 89%

β-blockers in pulmonary arterial hypertension: evolving concepts of right heart failure

Man

Handoko

2015

Eur Respir J

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“…Similarly, a single center experience of 94 patients (10 treated with β‐blockers, 84 not treated with β‐blockers) demonstrated safety of β‐blocker use in PH, but not efficacy. However, it was noted that use of β‐blockers was not associated with a significant increase in hemodynamic impairment, heart‐failure, hospitalization, syncope or death . Although, these two studies have demonstrated safety of β‐blockers in PH, there is a lack of clear data to prove the effectiveness of β‐blockers in PH.…”

Section: β‐Blockers For Cardiac Indicationsmentioning

confidence: 99%

“…However, it was noted that use of bblockers was not associated with a significant increase in hemodynamic impairment, heart-failure, hospitalization, syncope or death. 46 Although, these two studies have demonstrated safety of b-blockers in PH, there is a lack of clear data to prove the effectiveness of b-blockers in PH. Thus, there is a need for clinical trials and comparative studies to have a clear understanding of the role of b-blockers in the management of PH.…”

Section: Pulmonary Hypertensionmentioning

confidence: 99%

Trends in the off‐label use of β‐blockers in pediatric patients

Kaley

Aregullin

Samuel

et al. 2019

Pediatrics International

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The use of US Food and Drug Administration (FDA)‐approved drugs for the treatment of an unapproved indication or in an unapproved age group, or at doses or route of administration not indicated on the label is known as off‐label use. Off‐label use may be beneficial in circumstances when the standard‐of‐care treatment has failed, and/or no other FDA‐approved medications are available for a particular condition. In pediatric patients, off‐label use may increase the risk of adverse events as pharmacokinetic and pharmacodynamic data are limited in children. Approximately 73% of off‐label drugs currently prescribed for various conditions do not have sufficient scientific evidence for safety and efficacy. For example, β‐blockers are a class of drugs with FDA‐approval for very few indications in pediatrics but are commonly used for various off‐label indications. Interestingly, the proportion of off‐label use of β‐blockers in adults is at about 52% (66.2 million) of the total number of β‐blockers prescribed. The frequency of off‐label use of β‐blockers in children is also high with limited data on the indications as well as safety and efficacy. We present trends in off‐label use of β‐blockers in children to discuss drug safety and efficacy and include recommendations for pediatric providers.

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“…We calculated that during the ARIES 1 and 2 studies [21], the sildenafil dose finding study [22] and the sildenafil registration study [23] 14%, 12% and 6%, respectively, of PAH patients were treated with beta-blockers (unpublished data; courtesy of GlaxoSmithKline and Pfizer), often for reasons related to palpitations. THENAPPAN et al [24] and MORETTI et al [25] showed that beta-blocker therapy is not associated with adverse outcomes in patients with PAH. The recently published pilot study of carvedilol treatment in six PAH patients showed a significant improvement in RVEF and no negative effects on exercise capacity [26].…”

Section: Comparison With Earlier Studiesmentioning

confidence: 99%

Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study

et al. 2016

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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.

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Beta blocker for patients with pulmonary arterial hypertension: A single center experience

Cited by 13 publications

References 19 publications

β-blockers in pulmonary arterial hypertension: evolving concepts of right heart failure

β-blockers in pulmonary arterial hypertension: evolving concepts of right heart failure

Trends in the off‐label use of β‐blockers in pediatric patients

Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study

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