Chest
Volume 131, Issue 6, June 2007, Pages 1917-1928
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CLINICAL PRACTICE GUIDELINES
Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.06-2674Get rights and content

A consensus panel convened by the American College of Chest Physicians developed guidelines for the treatment of pulmonary arterial hypertension (PAH) that were published in 2004. Subsequently, several important clinical trials have been published, and new treatments have received regulatory approval. In addition, add-on and combination therapy are being explored, which promise to open new therapeutic avenues. This article, taking into consideration studies published prior to September 1, 2006, provides an update to the previously published guidelines. The original guidelines have been summarized, a discussion of new studies has been added, and the treatment algorithm has been revised to take into account recent developments in therapy. This update provides evidence-based treatment recommendations for physicians involved in the care of patients with PAH. Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended.

Section snippets

Update of Treatment Guidelines

A consensus panel convened by the ACCP developed guidelines for the diagnosis and treatment of PAH that were published in 2004.9 Subsequently, several important clinical trials have been published and new treatments have received regulatory approval. In addition, add-on and combination therapy are being explored, which promise to open new therapeutic avenues.

Therefore, the Health and Science Policy Committee of the ACCP authorized an update of the medical treatment guidelines.1 Lewis Rubin, MD,

Calcium-Channel Antagonists

A small number of patients with IPAH, who demonstrate a favorable response to acute vasodilator testing at the time of cardiac catheterization, will do well with calcium-channel blocker (CCB) therapy. Since publication of the original ACCP guidelines, an important article10 has further clarified the role of CCBs in the IPAH population. Sitbon and colleagues10 reported results of a retrospective analysis of 557 IPAH patients tested acutely with IV epoprostenol or inhaled nitric oxide. Using a

Epoprostenol

In a 12-week, prospective, multicenter, randomized, controlled, open-label trial,11 continuously IV infused epoprostenol plus conventional therapy (including oral vasodilators [CCBs], anticoagulation, diuretic, digoxin, and oxygen) was compared to conventional therapy alone in 81 patients with severe IPAH (NYHA class III or IV). Exercise capacity improved in the 41 patients treated with epoprostenol (median 6 min walk [6MW] distance, 362 m at 12 weeks, vs 315 m at baseline), and decreased in

Bosentan

The first randomized, double-blind, placebo-controlled, multicenter study22 of bosentan demonstrated an improvement in the 6MW distance of 70 m (from 360 ± 19 m at baseline to 430 ± 14 m at week 12; p < 0.05), whereas no improvement was seen with placebo (355 ± 25 m at baseline and 349 ± 44 m at week 12). Treatment with bosentan also improved cardiopulmonary hemodynamics and functional class. Asymptomatic increases in hepatic aminotransferases were observed in two bosentan-treated patients. In

Sildenafil

Sildenafil is a potent and highly specific phosphodiesterase 5 inhibitor that has been previously approved for erectile dysfunction. Several reports313233 of nonrandomized, single-center studies of PAH patients treated with long-term sildenafil suggested promise for sildenafil as a therapeutic agent. A double-blind, placebo-controlled study (the Sildenafil Use in Pulmonary Arterial Hypertension-1 study,34) randomly assigned 278 patients with symptomatic PAH (either idiopathic or associated with

Summary

The paradigm for treatment of PAH continues to advance rapidly. Multicenter randomized clinical trials (RCTs) have provided a basis for evidence-based practice. The treatment algorithm provided (Fig 1) attempts to summarize the current approach to therapy for PAH. The following brief overview, organized by functional class, is intended to facilitate clinical application of the algorithm. It should be noted that functional class is difficult to quantify, and may vary among patients and care

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      It causes a substantial clinical and economic burden, and PAH related hospital admissions decreased between 2001 and 2012, the mean charge and length of stay per PAH related admission have increased with no significant decline in inpatient mortality. However, significant improvements have been made in treatment recently [5–7]. Macitentan (CAS NO. 441798-33-0, Fig. 1) is a novel dual endothelin receptor antagonist, and inhibits contractile and proliferative responses to vascular smooth muscle and delays progression of PAH disease, including death, intravenous or subcutaneous injection of prostacyclin drug-like or PAH symptoms worsen [8–13].

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    Dr. Badesch has received grant monies from the National Institutes of Health. He has received grant monies from GlaxoSmithKline, United Therapeutics/LungRx, Actelion, Lilly/ICOS, Encysive, Pfizer, Myogen/Gilead, and CoTherix. He has received consultant fees from GlaxoSmithKline, Actelion, Myogen/Gilead, CoTherix, Pfizer, United Therapeutics, Mondo-Biotech, Biogen IDEC, PR Pharmaceuticals, Forrests Labs, Scios, Amgen, Biovale Pharmaceuticals/Clarus Health, and Johnson & Johnson. He has served on the speaker's bureau for GlaxoSmithKline, Actelion, Myogen/Gilead, Encysive, CoTherix, Pfizer, United Therapeutics, Mondo-Biotech, and Biogen IDEC. He has served on the board of directors for the Pulmonary Hypertension Association and the American Thoracic Society.

    Dr. Abman has served as a scientific advisor for INO Therapeutics.

    Dr. Simonneau has received grant monies from, served on the speaker's bureau for, and served on the advisory committees for Actelion, Pfizer, Schering, United Therapeutics, and GlaxoSmithKline.

    Dr. Rubin has received university grant monies from the National Heart, Lung, and Blood Institute. He has received grant monies from Actelion, Pfizer, United Therapeutics, Mondo-Biotech, MD Primer, and Gilead. He is a shareholder in LungRx. He has received consultant fees from the National Heart, Lung, and Blood Institute; Actelion; Pfizer; United Therapeutics; ProQuest; Bayer Schering; and Mondo-Biotech. He is on the advisory committees for Actelion, Pfizer, LungRx, MD Primer, and Encysive.

    Dr. McLaughlin has received grant monies from Actelion, Encysive, LungRx, Pfizer, and United Technologies. She has served on the speaker's bureau and advisory committees for Actelion, Gildead, and Pfizer.

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