Are beta blockers (beta-adrenergic blocking agents) used to treat pulmonary hypertension?

Beta-Blockers Are NOT Used to Treat Pulmonary Arterial Hypertension

Beta-blockers are not recommended for the treatment of pulmonary arterial hypertension (PAH) and remain controversial with insufficient evidence to support their routine use. 1

Current Evidence and Recommendations

Standard PAH Treatment Does Not Include Beta-Blockers

• Approved therapies for PAH target three specific biological pathways: the nitric oxide-cyclic guanosine monophosphate pathway (sildenafil, tadalafil, riociguat), prostacyclin pathway agonists (epoprostenol, treprostinil), and endothelin pathway antagonists (bosentan, ambrisentan). 2
• Current first-line treatment consists of combination drug therapy targeting multiple biological pathways simultaneously, which has improved 5-year survival from 34% in 1991 to more than 60% in 2015. 2
• Beta-blockers are not part of any established treatment algorithm for PAH. 1, 3

Why Beta-Blockers Are Avoided in PAH

• PAH patients are highly dependent on heart rate to maintain and increase cardiac output, making beta-blockade theoretically detrimental. 1
• The traditional concern is that reducing heart rate in PAH patients would compromise their ability to compensate for elevated pulmonary vascular resistance. 1
• Beta-blockers are considered relatively contraindicated in PAH because of possible negative effects on hemodynamics and exercise capacity. 4

The Ongoing Controversy

Preclinical Evidence Suggests Potential Benefit

• Animal studies in experimental rat models of PAH with right ventricular (RV) failure have shown beneficial effects of beta-blockers on RV function and morphology. 1
• The rationale is that chronic neurohormonal activation, while initially compensatory, may be detrimental long-term by causing down-regulation of β1-adrenergic receptors and impairing cardiac inotropic responsiveness. 1

Limited Clinical Data

• A retrospective study of 94 PAH patients with cardiac comorbidities found that beta-blocker use (28% of cohort) was not associated with worse outcomes (PAH-related hospitalization or all-cause mortality), but this cohort did not reflect typical PAH patients (older age, coronary artery disease). 1
• As of 2014, clinicians were not treating PAH patients with beta-blockers and were awaiting results from a phase II clinical trial (NCT01246037) testing bisoprolol in 30 IPAH patients. 1

Critical Care Considerations

When Beta-Blockers May Be Dangerous in PAH

• In hypertensive emergencies involving PAH patients who receive topical alpha-agonists (like phenylephrine), beta-blocker administration has been associated with pulmonary edema development. 1
• All patients who experienced cardiac arrests and death after phenylephrine administration were treated with beta-blocking agents. 1
• Beta-blockade impairs two critical compensatory mechanisms in PAH: the ability to increase heart rate and contractility to preserve cardiac output under increased afterload conditions. 1
• Labetalol use was specifically associated with death in these scenarios, while esmolol's brief duration of beta-blocking activity may have prevented progression from pulmonary edema to cardiac arrest. 1

Appropriate Vasopressor Management in PAH

• When managing critically ill PAH patients requiring vasopressors, vasopressin at replacement doses is recommended to offset potential drops in systemic vascular resistance when using inotropes like dobutamine. 5
• Preferred inotropes that have neutral or beneficial effects on pulmonary vascular resistance include dobutamine, milrinone, and epinephrine—not beta-blockers. 5

Important Distinction: Beta-Blockers in Hypertension vs. PAH

Beta-Blockers Remain Appropriate for Systemic Hypertension

• Beta-blockers are established first-line agents for systemic hypertension and provide documented cardiovascular prevention, particularly in combination with thiazide/thiazide-like diuretics. 1
• For hypertensive emergencies, esmolol and labetalol are recommended options in specific clinical contexts (acute aortic dissection, acute coronary syndrome). 1
• However, this recommendation applies to systemic hypertension, not pulmonary hypertension. 1

Bottom Line

Do not use beta-blockers to treat pulmonary arterial hypertension. 1 The evidence remains insufficient and controversial, with theoretical concerns about worsening hemodynamics outweighing any potential benefits from preclinical studies. Stick to guideline-directed PAH-specific therapies targeting the nitric oxide, prostacyclin, and endothelin pathways. 2 If a PAH patient has a separate indication for beta-blockers (such as coronary artery disease or systemic hypertension), this requires careful individualized assessment, but beta-blockers should never be initiated specifically to treat the PAH itself. 1