eMedicine Specialties > Pulmonology > Pulmonary Hypertension
Pulmonary Hypertension, Primary: Treatment & Medication
Updated: Aug 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Anticoagulation
- Several studies, using both univariate and multivariate analyses, show that survival is increased when the patient is treated with anticoagulant therapy, regardless of histopathologic subtype. However, these studies were retrospectively performed. No randomized, controlled clinical trials of anticoagulation in primary pulmonary hypertension (PPH) exist; thus, the data are mostly consensus-driven rather than based on prospective evidence-based medicine.
- Use warfarin to maintain an international normalized ratio of 1.5- to 2-times the control value, provided the patient has no contraindications to anticoagulation.
- Other oral agents
- Use digoxin therapy to improve right ventricular function in patients with right ventricular failure. However, no randomized controlled clinical study has been performed to validate this strategy for patients with PPH.
- Use diuretics to manage peripheral edema. The use of loop diuretics (eg, furosemide, bumetanide) requires potassium supplementation and close monitoring of serum potassium. Potassium-sparing diuretics may have a role in ameliorating the sometimes-intractable hypokalemia observed with daily diuretic use.
- Use oxygen supplementation in those patients with resting or exercise-induced hypoxemia. Use caution if patients have a left-to-right shunt via a patent foramen ovale (see Imaging Studies) because supplemental oxygen in these instances may provide little or no benefit.
- Conventional oral vasodilator therapy
- Until recently, CCBs had been the most widely used class of drugs for idiopathic pulmonary arterial hypertension (IPAH). These drugs are thought to act on the vascular smooth muscle to dilate the pulmonary resistance vessels and lower the pulmonary artery pressure. Several studies report clinical and hemodynamic benefits from the use of long-term calcium channel blockade. The use of these drugs produces a reduction in pulmonary vascular resistance by increasing the cardiac output and decreasing pulmonary artery pressure. It also improves the quality of life and survival rate, in patients who are proven "responders" to such therapy.
- Only use CCBs on patients without overt evidence of right-sided heart failure. A cardiac index of less than 2 L/min/m2 or elevated right atrial pressure above 15 mm Hg is evidence that CCBs may worsen right ventricular failure and, thus, are of no benefit. This is potentially harmful to patients with PPH.
- In general, high doses of CCBs are used in patients with PPH; however, only patients with an acute vasodilator response to an intravenous or inhaled pulmonary vasodilator challenge (eg, with adenosine, EPO, nitric oxide) derive any long-term benefit from CCBs (this corresponds to <20% of patients with PPH and probably <10% of patients with secondary, PPH-like pulmonary artery hypertension).
- Similarly, patients without an acute vasodilator response to a vasodilator challenge have a worse prognosis on long-term oral vasodilator therapy compared with those who have an initial response.
- Importantly, realize that the absence of an acute response to intravenous or inhaled vasodilators does not preclude the use of intravenous vasodilator therapy. In fact, continuous intravenous vasodilator therapy is strongly suggested for these patients because CCBs are contraindicated.
- This illustrates the importance of performing vasoreactivity testing in patients with PPH. Intravenous EPO or adenosine or inhaled nitric oxide are used most commonly for acute vasodilator testing. Oxygen, nitroprusside, and hydralazine should not be used as pulmonary vasodilator testing agents.
- Only up to 25% of patients with PPH demonstrate significant pulmonary vasoreactivity. If patients demonstrate vasoreactivity and are candidates for high-dose CCB therapy, administer a CCB challenge to stable patients to determine the vasodilator response. Perform this in the critical care unit with a balloon flotation catheter in the pulmonary artery. Administer oral nifedipine every hour (diltiazem can be used if resting tachycardia is present) until a 20% decrease in pulmonary artery pressure and pulmonary vascular resistance is observed or systemic hypotension or other adverse effects preclude further drug administration.
- Calculate the daily dosage requirement at half the total initial effective dose, and administer this every 6-8 hours. Typical doses of nifedipine and diltiazem can reach 240 mg/d and 900 mg/d, respectively. Use caution when withdrawing CCBs because rebound pulmonary hypertension has been reported with the cessation of vasodilator therapy.
- Approved pulmonary vasodilator medications currently available in the United States for PPH are as follows:
- Epoprostenol (Flolan) - Intravenous, parenteral (see Medication); prostacyclin analogue, sometimes referred to as a "prostanoid"8,9
- Treprostinil (Remodulin) - Intravenous or subcutaneous, parenteral (see Medication); prostacyclin analogue, sometimes referred to as a prostanoid10,11
- Iloprost (Ventavis) - Nebulized inhalation; prostacyclin analogue, sometimes referred to as a prostanoid12
- Bosentan (Tracleer) - Oral; endothelin antagonist, or ERA13,14
- Ambrisentan (Letairis) - Oral; endothelin antagonist, or ERA15
- Sildenafil (Revatio) - Oral PDE-5 inhibitor16
- Tadalafil (Adcirca) - Oral PDE-5 inhibitor17
- Note: While the above agents are often referred to as pulmonary vasodilator medications, their actions are likely pleiotropic, affecting endothelial function and intimal and smooth muscle proliferation. Their ability to dilate pulmonary arteries and thereby lower pulmonary arterial pressure is modest in most cases.
- Future therapies
- Clinical trials are under way to determine the safety and efficacy of several new therapies that include oral and inhaled prostanoids, phosphodiesterase inhibitors, and other novel agents.18
- Efforts are currently focused on prostacyclin analogues, newer endothelin antagonists, and phosphodiesterase-5 inhibitors (see below).
- Clinical guideline summaries
- (1) Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. (2) 2007 addendum19,20
- Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology21
Surgical Care
- A single- or double-lung transplant is indicated for patients who do not respond to medical therapy. Simultaneous cardiac transplantation may not be necessary even with severe right ventricular dysfunction; however, this is dependent on the transplant institution.
- Atrial septostomy is a palliative procedure that may afford some benefit to patients with deteriorating conditions. This procedure works by allowing interatrial right-to-left shunting to occur, thus delivering more overall oxygen content to the respiring tissues, albeit with a lower overall saturation.
Diet
- No specific diet is recommended; however, a low-sodium and low-fluid diet is recommended for those with significant volume overload due to right ventricular failure.
- Patients taking warfarin must limit their intake of vitamin K–containing foods, such as green leafy and coliform vegetables.
- L -arginine supplementation (a precursor to nitric oxide) may be helpful; however, more studies are needed to confirm its role in the management of IPAH.
Activity
- Limited data are available on cardiopulmonary rehabilitation. The generally accepted recommendation is that patients with pulmonary hypertension and heart failure perform mild symptom-limited aerobic activity and avoid complete bed rest. Isometric exercises (weight lifting) are contraindicated. A European study involving an intensive inpatient and outpatient exercise training and conditioning program demonstrated the safety and efficacy of exercise as a treatment modality for patients with PAH. While longer-term outcomes are needed, the PAH community considers exercise in moderation a safe and potentially efficacious adjunctive nonpharmacologic therapy.
Medication
Current pulmonary vascular therapies appear to exert their actions on the pulmonary circulation by mechanisms that remain poorly defined. Clearly, the magnitude of the pulmonary vasodilator actions of prostanoids and endothelin antagonists do not account for the degree of clinical benefit observed with these drugs. Rather, additional effects on the endothelial health of the pulmonary circulation and on the inhibition of pathologic intimal fibrosis and smooth muscle proliferation are likely to be the predominant mechanisms involved in the treatment responses.
Parenteral vasodilators
For patients in whom CCBs fail to respond or with an inability to tolerate CCBs with NYHA types III and IV right-sided heart failure.
CADD Legacy ambulatory infusion pump. Courtesy SIMS Deltec, St. Paul, Minn.
Epoprostenol (Flolan)
An analogue of PGI2 that was approved by the FDA in 1995 for use in patients with PPH. Has potent vasodilatory properties, an immediate onset of action, and a half-life of approximately 5 min. In addition to its vasodilator properties, also contributes to inhibition of platelet aggregation and plays a role in inhibition of smooth muscle proliferation. Latter effect may have implications for beneficial remodeling of pulmonary vascular bed. EPO is only FDA-approved medication for treatment of PPH.
Adult
Continuous IV infusion via permanent indwelling central venous catheter using a small, battery-powered infusion pump worn at the hip or carried in a backpack
Beginning dose: 2-4 ng/kg/min IV; depending on initial response; initiate under close observation in the ICU with right-sided heart flotation catheter in place
Subsequent dose: Titrate based on follow-up outpatient evaluation; currently, no upper limit has been defined; most patients derive optimal benefit with doses of 25-40 ng/kg/min; doses exceeding 40 ng/kg/min after 1 y of therapy are not uncommon
Pediatric
Administer as in adults
Coadministration with anticoagulants may increase bleeding risk because of shared effects on platelet aggregation
Documented hypersensitivity; hyaline membrane disease, dominant left-to-right shunt, respiratory distress syndrome
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Coadminister with anticoagulants whenever possible to reduce risk of thromboembolism; sudden discontinuation or reduction in therapy may result in rebound pulmonary hypertension
Treprostinil (Remodulin)
Used to treat PAH. Structurally very similar to EPO but stable at room temperature and has much longer half-life; therefore, can be given as an SC continuous infusion via a much smaller pump. Elicits direct vasodilation of pulmonary and systemic arterial vessels and inhibits platelet aggregation. Vasodilation reduces right and left ventricular afterload and increases cardiac output and stroke volume.
Recently FDA approved for IV use as a bioequivalent of subcutaneous treprostinil, using same delivery pump used for epoprostenol. Dosing is similar to SC delivery.
Adult
1.25 ng/kg/min SC via continuous infusion initially; may increase by 1.25 ng/kg/min qwk for 4 wk, then may increase by 2.5 ng/kg/min qwk; if initial dose not tolerated, decrease to 0.625 ng/kg/min, then slowly titrate upward; must slowly taper if discontinued (potential for severe rebound pulmonary hypertension and death)
Subsequent dose: Titrate based on follow-up outpatient evaluation; currently, no upper limit defined; most patients derive optimal benefit with 25-40 ng/kg/min; doses exceeding 40 ng/kg/min after 1 y of therapy are not uncommon; IV dosing is similar to that used in SC delivery
Pediatric
Not established; dosing is based on body weight
Additive hypotensive effect with antihypertensive agents or diuretics; may increase risk of bleeding with other antiplatelet drugs (eg, aspirin) or anticoagulants (eg, warfarin, heparin)
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause infusion site pain and irritation; common adverse effects include diarrhea, jaw pain, edema, vasodilatation, and nausea (typical effects of prostanoids); do not discontinue abruptly
Phosphodiesterase (type 5) Enzyme Inhibitor
The antiproliferative effects of the phosphodiesterase type 5 pathway, which regulates cyclic guanosine monophosphate hydrolysis, may be significant in the long-term treatment of pulmonary hypertension with PDE5 inhibitors such as sildenafil.
Sildenafil (Revatio)
Promotes selective smooth muscle relaxation in lung vasculature, possibly by inhibiting phosphodiesterase type 5 (PDE5). This results in subsequent reduction of blood pressure in pulmonary arteries and increase in cardiac output.
Adult
20 mg PO tid
Pediatric
Not established
Potentiates vasodilatory effect of NO, resulting in potentially fatal drop in blood pressure; coadministration with ketoconazole, erythromycin, or cimetidine increases plasma sildenafil concentrations; coadministration with rifampin decreases plasma levels of sildenafil
Documented hypersensitivity; concurrent or intermittent use of organic nitrates in any form
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects include headaches (16%), flushing (10%), upset stomach (7%), nasal congestion (4%), and a blue haze at the periphery of vision (3%); adverse effects occur more often in men taking the 100-mg dose; serious adverse effects occur in patients with severe heart disease and those who are taking nitrates; rates of MI were 1.7 and 1.4 per 100 man-years for sildenafil and placebo groups
Tadalafil (Adcirca)
Phosphodiesterase type-5 inhibitor indicated for improving and increasing exercise capacity in patients with WHO class I PAH. Increases cyclic guanosine monophosphate (cGMP), which is the final mediator in the nitric-oxide pathway.
Adult
40 mg PO qd (dividing dose to give more than once daily is not recommended)
CrCl 51-80 mL/min: 20 mg PO qd initially; may increase to 40 mg PO qd based on individual tolerability
CrCl <30 mL/min and on hemodialysis: Avoid use
Mild-to-moderate hepatic impairment (Child-Pugh class A or B): 20 mg PO qd initially
Severe hepatic impairment (Child-Pugh class C): Avoid use
Use with strong CYP3A4 inhibitors (eg, ritonavir): 20 mg PO qd initially; may increase to 40 mg PO qd based on individual tolerability
Pediatric
Not established
CYP450 3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, indinavir, ritonavir) may significantly increase levels of vardenafil; vardenafil potentiates hypotensive effect of nitrates or alpha-blockers; concurrent alcohol consumption may increase orthostatic hypotension risk
Documented hypersensitivity; concurrent or intermittent use of alpha-blockers (eg, doxazosin, terazosin, prazosin) or organic nitrates in any form
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Common adverse effects include headache, flushing, rhinitis, dyspepsia, or indigestion; assess cardiovascular status before use; caution with left ventricular outflow obstruction or conditions aggravated by hypotension; caution with hepatic or renal impairment (decrease dose); may cause prolonged or painful erection; may cause back pain or myalgias; sudden vision loss caused by nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with PDE-5 inhibitors following use for ED, analysis is ongoing to determine causality; sudden decreases or loss of hearing has been reported
Inhaled vasodilators
Inhaled PGI2 synthetic analogues are an alternative to parenteral administration and an attempt to limit systemic adverse effects.
Iloprost (Ventavis)
Synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. Indicated for pulmonary arterial hypertension (WHO class I) in patients with NYHA class III or IV symptoms to improve exercise tolerance and symptoms and to delay deterioration.
Adult
Initial: 2.5 mcg via nebulizer
Maintenance: If first dose tolerated, increase to 5 mcg/dose via nebulizer 6-9 times/d; do not administer more frequently than q2h
Note: Administration studied only with Prodose AAD system nebulizer
Pediatric
Not established
May increase hypotensive effect of vasodilators and antihypertensives; may increase bleeding risk when coadministered with anticoagulants
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor vital signs during initial treatment to decrease syncope risk; avoid eye and skin contact and oral ingestion; inhibits platelet function, but clinical relevance is unclear
Oral pulmonary hypertension agents
ERAs are alternative therapy to parenteral prostacyclin agents. Given PO. Competitively bind to ET-1 receptors endothelin-A and endothelin-B, causing reduction in PAP, PVR, and mean RAP. Indicated for treatment of PAH in patients with WHO class III or IV symptoms to improve exercise ability and decrease rate of clinical deterioration.
Bosentan (Tracleer)
First PO PPH therapy to be approved in United States. A mixed endothelin-A and endothelin-B receptor antagonist indicated for PAH, including PPH. In clinical trials, improved exercise capacity, decreased rate of clinical deterioration, improved functional class, and improved hemodynamics.
Improves pulmonary arterial hemodynamics by competitively binding to ET-1 receptors endothelin-A and endothelin-B in pulmonary vascular endothelium and pulmonary vascular smooth muscle. This leads to a significant increase in CI associated with a significant reduction in PAP, PVR, and mean RAP. These changes result in an improvement in exercise capacity (as measured by the 6-min walk test) and improved PPH symptoms.
Because drug has teratogenic potential and because of need for careful scrutiny in choosing appropriate candidates for ERA therapy, Tracleer can be prescribed only through the Tracleer Access Program. Call 1-866-228-3546.
Adult
62.5 mg PO bid for 4 wk, followed by 125 mg PO bid indefinitely
Pediatric
Not established; suggested doses include:
10-20 kg: 31.25 mg PO qd for 4 wk, followed by maintenance dose of 31.25 mg PO bid indefinitely
20-40 kg: 31.25 mg PO bid for 4 wk, followed by maintenance dose of 62.5 mg PO bid indefinitely
>40 kg: Administer as in adults
Toxicity may increase when administered concomitantly with inhibitors of isoenzymes CYP450 2C9 and CYP450 3A4 (eg, ketoconazole, erythromycin, fluoxetine, sertraline, amiodarone, cyclosporine A); induces isoenzymes CYP450 2C9 and CYP450 3A4, causing decrease in plasma concentrations of drugs metabolized by these enzymes (including glyburide and other hypoglycemics, cyclosporin A, hormonal contraceptives, simvastatin, and, possibly, other statins); hepatotoxicity increases with concomitant administration of glyburide
Regarding cyclosporin A, during first day of concomitant administration, trough concentrations of bosentan increase approximately 30-fold; steady-state bosentan plasma concentrations are 3- to 4-fold higher than in the absence of cyclosporine A
Regarding glyburide, an increased risk of elevated liver aminotransferase levels is observed in patients receiving concomitant therapy with glyburide
Documented hypersensitivity; coadministration with cyclosporin A or glyburide
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause a dose-related decrease in hemoglobin and hematocrit; hemoglobin levels should be monitored after 1 and 3 mo of treatment and then q3mo; overall mean decrease in hemoglobin concentration is 0.9 g/dL (change to end of treatment); most of this decrease of hemoglobin concentration is detected in first few weeks of treatment, and hemoglobin levels stabilize by 4-12 wk of treatment
In placebo-controlled studies of all uses of bosentan, marked decreases in hemoglobin (>15% decrease from baseline, resulting in values <11 g/dL) were observed in 6% of bosentan-treated subjects and 3% of placebo-treated subjects; in subjects with PAH treated with doses of 125 and 250 mg bid, marked decreases in hemoglobin occurred in 3% of bosentan-treated subjects compared with 1% in placebo-treated subjects
A decrease in hemoglobin concentration by at least 1 g/dL was observed in 57% of bosentan-treated subjects, compared with 29% of placebo-treated subjects; in 80% of subjects whose hemoglobin level decreased by at least 1 g/dL, the decrease occurred during the first 6 wk of treatment
During the course of treatment, hemoglobin concentration remained within normal limits in 68% of bosentan-treated subjects compared with 76% of placebo subjects (explanation for change in hemoglobin not determined, but hemorrhage or hemolysis did not appear to be the cause)
Check hemoglobin concentrations after 1 and 3 mo and every 3 mo thereafter; if a marked decrease in hemoglobin concentration occurs, further evaluation should be undertaken to determine cause and need for specific treatment
Causes at least 3-fold elevation of liver aminotransferase levels (ie, ALT, AST) in up to 11% of patients; may elevate bilirubin (serum aminotransferase levels must be measured prior to initiation of treatment and then qmo); caution in patients with mildly impaired liver function (avoid in patients with moderate or severe liver impairment)
Not recommended while breastfeeding; exclude pregnancy before initiating treatment and prevent thereafter by use of reliable contraception
Headache and nasopharyngitis may occur
Ambrisentan (Letairis)
Endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with WHO class II or III symptoms. Improves exercise ability and decreases progression of clinical symptoms. Inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to significant increase in cardiac index associated with significant reduction in pulmonary artery pressure, pulmonary vascular resistance, and mean right atrial pressure. Because of the risks of hepatic injury and teratogenic potential, only available through the Letairis Education and Access Program (LEAP). Prescribers and pharmacies must register with LEAP in order to prescribe and dispense. For more information, see http://www.letairis.com or call (866) 664-LEAP (5327).
Adult
5 mg PO qd initially; may increase to 10 mg PO qd if 5 mg/d tolerated; do not chew, crush, or split tab
Pediatric
Not established
Glycoprotein-P, OATP, UGTs (ie, 1A9S, 2B7S, 1A3S), CYP2C19, and CYP3A substrate; coadministration with CYP3A (eg, cyclosporine, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin) or 2C19 inhibitors (eg, omeprazole) may decrease elimination and therefore increase serum levels; CYP3A and 2C19 inducers (eg, rifampin) may increase metabolism and therefore decrease serum levels
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Common adverse effects include peripheral edema, nasal congestion, sinusitis, and facial flushing; caution with mild hepatic impairment or history of moderate-to-severe hepatic impairment; hepatic injury may occur (monitor bilirubin, ALT, and AST values at baseline and then monthly); may use in women of childbearing potential only after negative pregnancy test result and must use 2 reliable methods of contraception (unless tubal sterilization or Copper T 380A or LNg 20 IUD inserted); may decrease hemoglobin and hematocrit values (monitor at baseline, 1 mo, and then periodically)
More on Pulmonary Hypertension, Primary |
| Overview: Pulmonary Hypertension, Primary |
| Differential Diagnoses & Workup: Pulmonary Hypertension, Primary |
 Treatment & Medication: Pulmonary Hypertension, Primary |
| Follow-up: Pulmonary Hypertension, Primary |
| Multimedia: Pulmonary Hypertension, Primary |
| References |
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References
Dresdale DT, Schultz M, Michtom RJ. Primary pulmonary hypertension. I. Clinical and hemodynamic study. Am J Med. Dec 1951;11(6):686-705. [Medline].
Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med. Aug 29 1996;335(9):609-16. [Medline].
Tolle JJ, Waxman AB, Van Horn TL, Pappagianopoulos PP, Systrom DM. Exercise-induced pulmonary arterial hypertension. Circulation. Nov 18 2008;118(21):2183-9. [Medline].
[Guideline] McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. Jul 2004;126(1 Suppl):14S-34S. [Medline].
[Guideline] Rubin LJ. Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. Jul 2004;126(1 Suppl):4S-6S. [Medline].
[Guideline] 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 and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation. Apr 28 2009;119(16):2250-94. [Medline].
Torbicki A, Kurzyna M, Kuca P, et al. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation. Aug 19 2003;108(7):844-8. [Medline].
Oudiz RJ, Farber HW. Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J. Apr 2009;157(4):625-35. [Medline].
Shapiro SM, Oudiz RJ, Cao T, et al. Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J Am Coll Cardiol. Aug 1997;30(2):343-9. [Medline].
Oudiz RJ, Schilz RJ, Barst RJ, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest. Aug 2004;126(2):420-7. [Medline].
Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. Mar 15 2002;165(6):800-4. [Medline].
Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. Aug 1 2002;347(5):322-9. [Medline].
Galie N, Hinderliter AL, Torbicki A, et al. Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension. J Am Coll Cardiol. Apr 16 2003;41(8):1380-6. [Medline].
Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. Mar 21 2002;346(12):896-903. [Medline].
[Best Evidence] Galie N, Olschewski H, Oudiz RJ, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. Jun 10 2008;117(23):3010-9. [Medline].
[Best Evidence] Simonneau G, Rubin LJ, Galie N, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. Oct 21 2008;149(8):521-30. [Medline].
Galie N, Brundage BH, Ghofrani HA, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. Jun 9 2009;119(22):2894-903. [Medline].
Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med. Feb 15 2004;169(4):441-7. [Medline].
[Guideline] Badesch DB, Abman SH, Ahearn GS, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. Jul 2004;126(1 Suppl):35S-62S. [Medline].
[Guideline] Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. Jun 2007;131(6):1917-28. [Medline].
[Guideline] Galie N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. Dec 2004;25(24):2243-78. [Medline].
Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med. Feb 1 1996;334(5):296-302. [Medline].
Gaine S. Pulmonary hypertension. JAMA. Dec 27 2000;284(24):3160-8. [Medline].
Rich S, Dantzker DR, Ayres SM, Bergofsky EH, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. Aug 1987;107(2):216-23. [Medline].
Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation. Jul 24 2001;104(4):429-35. [Medline].
Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Gas exchange detection of exercise-induced right-to-left shunt in patients with primary pulmonary hypertension. Circulation. Jan 1 2002;105(1):54-60. [Medline].
Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Pulmonary function in primary pulmonary hypertension. J Am Coll Cardiol. Mar 19 2003;41(6):1028-35. [Medline].
Further Reading
Keywords
primary pulmonary hypertension, idiopathic pulmonary arterial hypertension, IPAH, idiopathic pulmonary hypertension, elevated pulmonary artery pressure, thrombotic pulmonary arteriopathy, TPA, plexogenic pulmonary arteriopathy, PPH, precapillary pulmonary hypertension, endothelin receptor antagonists, ERAs, endothelin-receptor antagonists, pulmonary hypertension, portal hypertension, pulmonary arteriopathy, pulmonary artery hypertension, PAH, pulmonary arterial hypertension, portopulmonary hypertension, CREST syndrome
