One of the difficulties for people diagnosed with pulmonary hypertension (PH) is their limited independence in many cases. Just performing routine physical activities can leave them breathless.1
Experts: Drug Helps Improve Symptoms
But an experimental medication not yet approved for PH may help people increase their level of activity without exacerbating symptoms. The drug, known as sitaxsentan, enabled patients in an ongoing clinical trial2 to walk an additional 20 meters (about 22 yards) in a special test. By comparison, those taking only placebo in the study walked 38 fewer meters (about 41 and a half fewer yards) in the test.
Vallerie McLaughlin, MD, and colleagues at the University of Michigan Hospital in Ann Arbor released interim findings of the study at a meeting of the American College of Rheumatology last month. "Sitaxsentan was shown to significantly improve six-minute walk distance, as well as hemodynamics [mechanisms involved in blood circulation], such as cardiac index and pulmonary vascular resistance for patients with pulmonary hypertension related to connective tissue disease," McLaughlin said.
The positive effect this medication had on these patients "means they can take care of themselves—do their own grocery shopping," she added.
IPF and Connective Tissue Disease
Most of the patients in the study had scleroderma, a connective tissue disease characterized by an excessive accumulation of tissue and inflammation.3 But some also had lupus, a chronic autoimmune disease that results in inflammation and other symptoms like achy or swollen joints, skin rashes, seizures, and hair loss.4
Scleroderma5 and lupus6 are diseases that cause PH. When the cause is known, doctors refer to secondary pulmonary hypertension. On the other hand, primary pulmonary hypertension, which is less common, involves cases in which PH occurs on its own and has no known cause.
McLaughlin says while epoprostenol (Flolan/GlaxoSmithKline) has been shown to be effective for these patients, it requires the placement of a central catheter and continuous IV, which patients might often not be able to tolerate. Sitaxsentan is an oral medication designed to be taken daily.
In the study, 178 people with pulmonary hypertension are taking either the drug or a placebo to determine safety and efficacy. All patients had NYHA class II or III pulmonary hypertension, classified as having limited physical ability that ranged from slight to marked. The findings released last month involved 42 patients diagnosed with PH related to a connective tissue disease. They were assigned at random to receive one of two doses of sitaxsentan—100 or 300 mg—or placebo, then were instructed to walk as far as they could for a total of 6 minutes.
In addition to the improvements in walking distance demonstrated by the patients taking either dose of the medication, 25 percent of those in the treatment group improved by one NYHA functional class, meaning if they had marked limited physical ability at the start of the study, they had slight to mild ability afterwards. That compares to 11 percent of the patients given placebo.
How it Works
The drug works, researchers say, by targeting endothelin, a protein that contributes to blood vessel constriction in the lungs. Endothelin is highly activated in people with pulmonary hypertension.7
Bosentan (Tracleer/Actelion), a currently approved PH drug, targets both endothelin receptors. "I think it's important we look at these agents that don't hit both receptors," said Fredrick Wigley, MD, a professor of Medicine in the division of Rheumatology at Johns Hopkins University who was not involved in this study. "… It's nice to have an option that may have a different mechanism that may potentially be safer."
Sitaxsentan is manufactured by Encysive Pharmaceuticals.
1. Pulmonary Hypertension Association. What is PH? Available at: http://www.phassociation.org/Learn/What-is-PH/. Accessed November 11, 2004.\
2. McLaughlin V, Hill N, Tapson VF et al. Sitaxsentan improves 6MW in patients with pulmonary arterial hypertension (PAH) related to connective-tissue disease (CTD). American College of Rheumatology/Association of Rheumatology Health Professionals 68th Annual Scientific Meeting. 2004 Oct 16-21. San Antonio, TX.
3. Scleroderma Research Foundation. What is Scleroderma? Available at: http://www.srfcure.org/srf/patients/whatis.htm. Accessed November 11, 2004.
4. Lupus Foundation of America. Frequently Asked Questions about Lupus. Available at: http://www.lupus.org/education/faq.html#1. Accessed November 11, 2004.
5. Merck Manual. Pulmonary Hypertension.
6. Mulherin D, Bresnihan B. Systemic lupus erythematosus. Baillieres Clin Rheumatol 1993 Feb;7(1):31-57.
7. Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 2004 Feb 1;61(2):227-37.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
