The past decade has seen remarkable improvements in therapy since the American College of Chest Physicians (ACCP) first formed a consensus panel to study the pathobiology, diagnosis, and treatment of primary pulmonary hypertension 10 years ago. Selection of the most appropriate therapy is still a complex matter, however.An interdisciplinary expert committee convened by the ACCP recently developed guidelines regarding medical therapy for PAH. The document was published in a supplement to the July issue of the journal Chest. The guidelines were developed with the support of Actelion Pharmaceuticals U.S., Encysive Pharmaceuticals, and GlaxoSmithKline.
The medical treatment of pulmonary arterial hypertension (PAH) has historically been difficult. Through the mid-1980s, idiopathic PAH (IPAH), formerly known as primary pulmonary hypertension (PPH), was associated with a median survival of approximately 2.8 years from the date of diagnosis.
The estimated prevalence of PAH in the United States is greater than 100,000, with several thousand new cases diagnosed each year. Although PAH could potentially affect anyone, the incidence is highest among women aged 20 to 40 years.
The American College of Chest Physicians (ACCP) first formed a consensus panel to study the pathophysiology, diagnosis, and treatment of PPH 10 years ago. Fortunately, the past decade has seen remarkable improvements in therapy. Selection of the most appropriate therapy is still a complex matter, however.
An interdisciplinary expert committee convened by the ACCP recently developed guidelines regarding medical therapy for PAH. The document was published in a supplement to the July issue of the journal Chest. The guidelines were developed with the support of Actelion Pharmaceuticals U.S., Encysive Pharmaceuticals, and GlaxoSmith-Kline.
The panel adopted the nomenclature developed at the 1998 World Health Organization International Conference and updated at the 2003 Third World International Conference, replacing the term primary pulmonary hypertension with the term idiopathic pulmonary arterial hypertension. Pulmonary arterial hypertension refers to IPAH and PAH associated with other conditions, such as scleroderma.
Those with PAH should undergo acute vasoreactivity testing using a short-acting vasodilator such as intravenous epoprostenol sodium (Flolan, GlaxoSmithKline), adenosine, or inhaled nitric oxide, said Richard Channick, M.D., an associate professor of medicine at the University of California at San Diego Medical Center, and codirector of the PAH program at UCSD. In the absence of right-heart failure, persons with PAH who demonstrate a favorable acute response to a vasodilator with a fall in pulmonary artery pressure to near-normal levels should be considered candidates for a trial of calcium-channel blockers (CCBs), he said. The ACCP committee said that nifedipine, diltiazem, and amlodipine (Norvasc, Pfizer) are the most commonly used CCBs, and verapamil should be avoided because of negative inotropic effects.
Patients with PAH in New York Heart Association (NYHA) functional class III who are not candidates for, or who have failed, therapy with CCBs are candidates for long-term therapy with bosentan (Tracleer, Actelion Pharmaceuticals), Channick continued. The authors of the guidelines said that these patients are also candidates for therapy with epoprostenol, subcutaneous treprostinil (Remodulin, United Therapeutics), inhaled iloprost (Berlex Laboratories), or beraprost (Toray Industries). The latter two agents are not currently FDA-approved, said Channick.
The treatment of choice for those in NYHA functional class IV who are not candidates for, or who have failed, CCB therapy is epoprostenol, said Channick. Treatment with sildenafil (Viagra, Pfizer) for persons with PAH who have failed or are not candidates for other available therapies should be considered, the ACCP panel said.
Community pharmacists can counsel PAH patients about their medicationsparticularly CCBs, which may be prescribed at higher doses than usual for the treatment of PAH, said Ronald DeBellis, Pharm.D., an associate professor of pharmacy practice at the Massachusetts College of Pharmacy and Health Science.
Pharmacists can also advise patients about PAH drugs' potential side effects, DeBellis added. For example, he said, bosentan therapy is associated with an elevation in liver enzymes. Patients who have not had their liver enzyme levels checked should be encouraged to do so.
DeBellis pointed out that patients with PAH for whom sildenafil is prescribed may feel uncomfortable. Community pharmacists can educate patients regarding sildenafil's role in dilating the pulmonary arteries versus its use as a therapy for erectile dysfunction, he said.
Hospital pharmacists, too, have a significant role in the management of PAH, said Channick. Depending on the size of the institution and the level of expertise of the nursing staff, hospital pharmacists may need to guide those with less experience in working with epoprostenol, he said.
PAH is an underdiagnosed condition, said DeBellis, and, until now, no in-depth review of the literature with a focus on disease class has been done. He explained that case reports and reviews by experts in the field previously served as the guiding force for the management of PAH. With the establishment of the new guidelines, health professionals now have at their disposal a peer-reviewed and evidence-based treatment algorithm that makes use of available pharmacotherapies, he concluded.
Charlotte LoBuono. Pulmonary hypertension guidelines include latest drugs. Drug Topics Aug. 23, 2004;148:29.