11.17.2025

Managing Pulmonary Hypertension in Hospice Care: A Revision

This month, we are pleased to present a renewed look at one of our popular Palliative Pearls cases, originally featured in March 2019. In this updated edition, we have integrated insights from the latest published literature to enhance your learning experience.

PATIENT CASE

JV is a 66-year-old woman with a primary diagnosis of pulmonary arterial hypertension (PAH) (WHO functional class III), and history of scleroderma and no known drug allergies. The patient has seen a significant decline over the past few months, where she is starting to become short of breath and fatigued even at rest. She lives at home with her husband where she is being seen for the first time by the home hospice nurse. JV is prescribed Letairis® (ambrisentan) 10mg by mouth daily and Adcirca® (tadalafil) 40mg by mouth daily to manage PAH. These medications are related to the patient’s primary diagnosis of PAH. The home hospice nurse is unsure if the medications should be continued on hospice care or if there are formulary or more cost-effective alternatives.

INTRODUCTION

Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) higher than 20 mmHg at rest. In PH, vascular remodeling occurs and is due to cardiovascular, pulmonary or thromboembolic complications.1,2 The World Health Organization (WHO) classifies PH into five groups, which are categorized according to similar pathophysiologic changes, clinical presentation, and available therapies.1 In addition, similar to patients with heart failure classified based on severity of symptoms using the New York Heart Association (NYHA) Functional Classification,16 patients with PH are further classified into one of 4 functional classes based on exercise capacity.5

Classification—Etiology Groupings6

  • Group 1–Pulmonary arterial hypertension (PAH): Commonly caused by idiopathic (IPAH) and heritable PAH, drugs and toxins, connective tissue diseases (e.g., scleroderma, rheumatoid arthritis, systemic lupus erythematosus, Raynaud disease), human immunodeficiency virus (HIV), portal hypertension, or congenital heart disease.
  • Group 2–PH due to left heart disease (LHD): Commonly caused by left ventricular systolic or diastolic dysfunction, and mitral and aortic valve disease.
  • Group 3–PH due to chronic lung disease and/or hypoxemia: Commonly caused by chronic obstructive pulmonary disease (COPD) or emphysema, interstitial lung disease, pulmonary fibrosis with emphysema.
  • Group 4–PH due to pulmonary artery obstruction: Commonly caused by chronic thromboembolic PH or other obstructions (e.g., sarcomas or tumors).
  • Group 5–PH due to unclear multifactorial mechanisms: Commonly caused by chronic hemolytic anemia (e.g., sickle cell disease), myeloproliferative disorders, systemic disorders (e.g., sarcoidosis), metabolic disorders (e.g., glycogen storage disease), chronic kidney disease, or miscellaneous causes.

Classification—Functional Classes (Exercise Capacity)5

  • Class I: Without resulting limitations of physical. Ordinary physical activity does not cause undue fatigue or dyspnea, chest pain, or heart syncope.
  • Class II: Slight limitation of physical. Comfortable at rest. Ordinary physical activity results in undue fatigue or dyspnea, chest pain, or heart syncope.
  • Class III: Marked limitation of physical. Comfortable at rest. Less than ordinary physical activity causes undue fatigue or dyspnea, chest pain, or heart syncope.
  • Class IV: Inability to carry on any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest. Discomfort is increased by physical activity.

Symptom Presentation

Patients with PH typically present with exertional dyspnea, lethargy, and fatigue. As PH progresses symptoms of right ventricle failure develop including exertional chest pain, exertional syncope, elevated jugular venous pressure, pleural effusion, weight gain from edema, anorexia and/or right-upper-quadrant pain and swelling (ascites) due to hepatic congestion. Less common symptoms include cough, hemoptysis, and hoarseness due to compression of the recurrent laryngeal nerve by the distended pulmonary artery.1

As discussed in the Management section below, knowing a patient’s PH classification (etiology group and functional class) will direct to the most appropriate therapy. Observation of a patient can inform a functional class designation; however, the group of PH may not always be known. Becoming familiar with the common underlying cause(s) (See Classification—Etiology Groupings) and recognizing them in patients can ultimately guide palliative management in the absence of an official diagnosis

MANAGEMENT

Primary Therapy

Management of all groups of PH begins with primary therapy (standard or supportive therapy). Primary therapy is directed at the underlying cause of the PH. Effective or common therapies include oxygen, diuretics, anticoagulants, and digoxin. Patients in all groups may benefit from primary therapy, however there are some primary therapy options that are particularly effective for each specific group type. Consider the risks and benefits of each of the following primary therapies:7

  • Oxygen is recommended in group 2 PH (LHD) and group 3 PH (chronic lung disease and/or hypoxemia).
  • Diuretics may be beneficial in patients with fluid retention from PH-related right ventricular failure. First line diuretic treatment includes loop diuretics (furosemide, bumetanide, or torsemide) with special attention to dosage ranges to prevent excessive diuresis. For patients with diuretic resistance, thiazide diuretics may be added as combination therapy (e.g., metolazone or hydrochlorothiazide).8
  • Anticoagulants (typically warfarin) are recommended in group 4 PH (chronic thromboembolic).9
  • Digoxin may be beneficial in patients with left ventricle systolic dysfunction.

Advanced Therapy

Assess response to primary therapy as well as disease severity to determine whether advanced therapy is indicated. Advanced therapy is directed at the pulmonary hypertension itself, producing pulmonary vasodilation, rather than the underlying cause.5 Advanced therapy is broadly accepted for group 1 PAH, however, must be considered on a case-by-case basis for patients with group 3, 4 or 5 PH, after weighing the risks versus the benefits.

Importantly, evidence supporting advanced therapy is resultant from study patients with group 1 PAH, and not with other groups, and should only be prescribed by experienced clinicians. Advanced therapy should be avoided in group 2 as it may be harmful.5 Medications and available dosage forms include:5,9,10

There is no best practice method for selecting an appropriate agent. The choice should be based on patient-specific factors, potential drug interactions with medications treating other comorbidities, as well as clinicians’ expertise and clinical experience.

For patients with group 1 PAH, it is recommended to review a patient’s history to determine if a vasoreactivity test has been previously performed to identify those who may respond to calcium channel blockers (CCBs), less expensive options with fewer adverse effects than other advanced therapies:

  • Initiate CCB therapy for patients with positive vasoreactivity.
  • For those with negative vasoreactivity, consider other advanced therapy based on functional class, as discussed below:5,11,12

Combination Therapy11,13

For patients with progressive or refractory disease, combination therapy with a second, and rarely third, agent of a different class is appropriate. Note that it is contraindicated to combine PDE type 5 inhibitors and guanylate cyclase stimulants due to an unfavorable safety profile.5

CONSIDERATIONS FOR HOSPICE CARE

There are several factors to consider as PH disease advances and when transplant and other surgical procedures, as well as correction or management of underlying causes, are no longer conducive to the goals of care. Few, if any, hospice formularies include PH medications with no direct formulary alternatives. Recognizing that hospice coverage of medications is formulary agnostic, decisions on PH medications need to be shared decisions that balance short-term symptom management benefits with the following:

  • Primary Therapy & Symptom-Based Care: Perform a medication history to identify current medications and unmanaged symptoms. Maximize current therapy, where feasible, and add palliative therapies such as oxygen, opioids, and benzodiazepines.
  • Quality of Life: While advanced therapies have proven to contribute to disease modification, such therapies can have a dramatic impact on quality of life due to side effects such as hypotension, nausea, flushing, headaches, and dizziness.2
  • Cost Factors: Advanced therapies can cost upward of $50,000 per year, creating difficulties for patients and caregivers, insurers, and hospice agencies.2
  • Discontinuation Process: Deprescribing advanced therapies can be complicated with limited published guidance on proper steps. In addition, discontinuation of such therapy can increase anxiety in patients due to concern of rapid development of distressing symptoms. Experts recommend the following approach:5,13,14,16
  1. Reduce PH medication doses in increments (e.g., 25% at a time), with close monitoring for symptoms as a new steady state is achieved.
    • Identify the medication’s elimination half-life (the time required for the concentration of a medication in the body’s plasma to decrease by half)
    • Calculate “steady state”—it takes approximately 5 half-lives for the body to reach this new steady state.
    • Wait until the “steady state” period has elapsed, then assess and manage symptoms before proceeding with another dose/rate reduction.
    • EXAMPLE: Oral ambrisentan has an elimination half-life (T ½) of ~ 9 hours so it will take about 45 hours (~2 days) before the body will reach its new steady state after decreasing the dose. Wait until 2 days have elapsed, then assess and manage symptoms before proceeding with another dose reduction.
      Elimination half-lives and estimates of new steady states for common PH medications are summarized below.5,16

  1. Anticipate withdrawal symptoms including anxiety, chest pain, and dyspnea.
  2. Consider titration of and ready access to medications that manage anticipated symptoms such as opioids, oxygen, and benzodiazepines.

PATIENT CASE ASSESSMENT

Applying the standard of care guidelines to this patient case, the following assessments were made:

  • Patient JV presented with Group 1 pulmonary arterial hypertension, functional class III with symptoms of worsening shortness of breath and fatigue even at rest. She is being managed with the preferred advanced therapy, identified above, for functional class III—dual combination therapy with ambrisentan and tadalafil.
  • The hospice nurse requests identification of formulary or cost-effective alternatives for ambrisentan and tadalafil. Few, if any, hospice formularies include PH medications nor direct formulary alternatives, so focus is shifted to identifying cost-effective alternatives and/or discontinuation of therapy.
    • JV has a negative vasoreactivity history documented in her chart, so calcium channel blockers are not a therapy option.
    • A review of alternative advanced therapies for functional class III does not leave many cost-effective options. Alternatives include other endothelin receptor antagonist-PDE type 5 inhibitor combinations or single agent oral therapy. Patients with rapid or progressive disease may also benefit from prostacyclin agonists and analogs.
      • The PDE type 5 inhibitor sildenafil may be considered a cost-effective alternative to tadalafil.
      • The endothelin receptor antagonist ambrisentan does not have a cost-effective alternative.
    • Consider discontinuing advanced therapy (ambrisentan and tadalafil)
      • Benefits of discontinuation: decreased adverse effects and drug interactions; cost savings.
      • Risks of discontinuation: increased frequency of symptom assessment and need to identify and administer appropriate therapy accordingly; necessity of incremental tapering to withdraw advanced therapy—do not abruptly discontinue.
      • Anticipate withdrawal symptoms including anxiety, chest pain, and dyspnea.
      • Ensure ready access to medications that manage anticipated symptoms such as opioids, oxygen, and benzodiazepines.
    • JV reports uncontrolled shortness of breath and fatigue. Review of her current primary therapy reveals she is already receiving oxygen 2 liters/min via nasal cannula as needed and furosemide 80mg by mouth twice daily.
      • Supplemental oxygen is indicated for group 3 PH with hypoxemia with a goal of maintaining an oxygen saturation of 90 to 96 percent.2 Recognizing that oxygen saturation is likely not being measured routinely, it is recommended to trial continuous administration with reassessment of shortness of breath to determine a path forward.
      • Diuretics reduce hepatic congestion, peripheral edema, and pleural effusions, thus improving shortness of breath. Furosemide therapy is not maximized and can be titrated to patient comfort up to 600mg/day, as tolerated.5 Monitor blood pressure with dose titrations—diuretic-induced volume depletion may lead to hypotension that can precipitate an acute PH crisis.2,3
      • Consider initiating a low-dose opioid, like morphine, for shortness of breath.
      • Achieving control of shortness of breath may also improve patient fatigue. Literature supporting pharmacotherapy for fatigue (corticosteroids and psychostimulants like methylphenidate and modafinil), are mainly in patients with cancer.17 Screening patients on hospice for depression is universal, however. Assess any other signs and symptoms of depression and the patient’s prognosis to determine if initiating an antidepressant may be appropriate.

The decision to continue advanced therapy with increasing symptoms on hospice care is multifactorial. There is often a combination of medications that reduce the risks of disease progression and hospitalization that also palliate symptoms.10 During hospice care, therapy that is curative or has long-term outcomes is typically discontinued while therapy that provides symptom management and comfort is continued. Other factors to consider are adverse effects and interactions associated with therapy, quality of life and most importantly, goals of care. Only when all these factors are balanced may an informed decision be made on how to manage advanced therapy.

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REFERENCES

  1. Boucekkine H, et al. Group 1 Pulmonary Hypertension (Pulmonary Arterial Hypertension). In: Medscape, Talavera F, Mosenifar Z (Eds). Jul 16, 2025. Article link  
  2. Mahesh Chandrasekhar MD1, Anirudh Rao MD2, George Ruiz MD3, Hunter Groninger MD2. Palliative Care Issues in Pulmonary Arterial Hypertension. Palliative Care Network of Wisconsin. [Online] June 17, 2025. [Cited: 7 11, 2025.] 
  3. Barot N, et al. Group 2 Pulmonary Hypertension. In: Medscape, Talavera F, Mosenifar Z (Eds). August 26, 2025. Article link  
  4. Klings ES. Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults. In: UpToDate, Mandel J, Lee JS, Finlay G (Eds), Wolters Kluwer. (Accessed October 14, 2025) 
  5. Hopkins W, Rubin LJ. Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy. In: UpToDate, Mandel J, Finlay G (Eds), Wolters Kluwer. (Accessed October 14, 2025) 
  6. Rubin LJ, Hopkins W. Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults. In: UpToDate, Mandel J, Finlay G (Eds), Wolters Kluwer. (Accessed October 13, 2025) 
  7. Frantz RP, DuBrock HM. Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Treatment and prognosis. In: UpToDate, Mandel J, Lee JS, Finlay G (Eds), Wolters Kluwer. (Accessed October 14, 2025) 
  8. Hansen, Lillian et al. “Volume Management in Pulmonary Arterial Hypertension Patients: An Expert Pulmonary Hypertension Clinician Perspective.” Pulmonary therapy vol. 4,1 (2018): 13-27. doi:10.1007/s41030-018-0052-z. 
  9. Clinical Resource, Meds for Pulmonary Arterial Hypertension. Pharmacist’s Letter/Prescriber’s Letter. March 2017. 
  10. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. c2025-[cited 2025 Oct]. Available from: http://www.clinicalkey.com.  
  11. Klinger JR. Therapy for Pulmonary Arterial Hypertension in Adults. Chest. 2019;155(3):565-586. https://doi.org/10.1016/j.chest.2018.11.030. 
  12. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol 2009;53:1573– 619. 
  13. Burks M, Stickel S, Galie N. Pulmonary Arterial Hypertension: Combination Therapy in Practice. Am J Cardiovasc Drugs. 2018;18(4):249-257. https://pmc.ncbi.nlm.nih.gov/articles/PMC6028878/    
  14. Chandrasekhar M, Rao A, Ruiz G, Groninger H. Palliative Care Issues in Pulmonary Arterial Hypertension. In: Palliative Care Network of Wisconsin Fast Facts. June 17, 2025. Article link​ 
  15. Bartlett C, Landzaat L, in cooperation with the COPE Collaborative*. Prostacyclin Withdrawal in Pulmonary Hypertension. In: Palliative Care Network of Wisconsin Fast Facts. April 4, 2025. Article link  
  16. American Heart Association. Classes and Stages of Heart Failure. May 21, 2025. Article link 
  17. Lexi-Drugs. UpToDate Lexidrug. UpToDate Inc. https://online.lexi.com. Accessed Nov 11, 2025. 
  18. Bruera E, Yennurajalingam S. Overview of fatigue in palliative care. In: UpToDate, Smith TJ, Givens J (Eds), Wolters Kluwer. (Accessed Nov 12, 2025) 

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