Keeping Pace With Evidence-Based Medicine: Pulmonary Hypertension Guideline Updates and Beyond

According to experts at the 2014 American College of Chest Physicians (ACCP) meeting, evidence-based guidelines are increasingly becoming “living” documents that are continuously updated. Darren Taichman, MD, PhD, executive deputy editor of the Annals of Internal Medicine and adjunct associate professor of medicine, Perelman School of Medicine, University of Pennsylvania, presented updates to the ACCP guideline for diagnosis and treatment of pulmonary hypertension (PH) during a panel discussion.

PH is a disease in which it is critically important to ensure that an accurate diagnosis is established, noted Dr Taichman. Appropriate diagnosis ultimately informs the appropriate therapy. Treatments for one type of PH, such as pulmonary arterial hypertension, may not work for another type of PH, such as chronic hypoxemic lung disease.

Functional classification of PH severity is somewhat subjective, and has some limitations, but in general is clinically useful. This classification, which is known as the World Health Organization Functional Classification (FC), is separated into 4 categories:

• In group I, patients have ordinary activity, no limitation or symptoms; in these patients no pharmacotherapy is indicated, only monitoring.
• In group II, patients may have ordinary activity, with slight limitations due to undue symptoms like shortness of breath, chest pain, fatigue and near-syncope.
• In group III, patients have less than ordinary activity, more symptoms, and perhaps even presyncope with marked limitation.
• In group IV, any activity is limited, and patients may even have symptoms at rest.

In general, treatment PH must begin with vasoreactivity testing. Patients who experience lung vasodilation in response to nitrous oxide inhalation should be considered as candidates for calcium channel blocker therapy. However, in an important caveat, Dr Teichmann stated, “Empirical therapy without vasoreactivity testing is dangerous and potentially even fatal in some patients.”

Several classes of medications are available for treatment of PH. These include endothelin receptor antagonists, soluble guanylate cyclase stimulators, and phosphodiesterase-5 inhibitors. Intranveous agents are also available.

Some fundamentals of treatment, as outlined by Dr Taichmann, include the following:

• For FC III patients who are treatment-naïve, the guideline authors advise monotherapy with ambrisentan, bosentan, macitentan, riociguat, sildenafil, or tadalafil. Sicker, and rapidly progressing patients, however, may be better candidates for an intravenous or subcutaneous parenteral prostanoid.
• In FC IV, initial monotherapy is recommended, unless a patient is unable to or does not want to use a parenteral prostanoid. In these cases, an inhaled prostanoid plus an endothelin receptor antagonist may be a more appropriate option. In some situations, based on emerging data, combination therapy may be warranted.

Also important are influenza vaccinations, and pneumococcal vaccinations in patients with PH. Pregnancy and nonessential surgery should be avoided, and supplemental oxygen may be necessary during air travel.

The new treatment guideline in PH is subject to some limitations. For example, supportive therapy with diuretics, digoxin, oxygen, and anticoagulants is not covered by the guideline. Dr Taichmann recommended referring to the 2007 guidelines for information on use of these supplemental treatments.

With evolving guidelines in many different treatment areas, the ACCP is moving toward living guidelines that keep pace with a rapidly changing evidence landscape, according to Daniel Oulette, MD, FCCP, leader of ACCP’s guideline oversight committee.

When developing any guideline, investigators look at 4 important questions:

• What is the population of interest?
• What interventions should we consider?
• What is the comparison group?
• What is the specific outcome we are looking at?

Establishing the strength of evidence behind each recommendation is an important priority for the ACCP. However, more recently, guidelines are becoming “a mix between consensus statements and guidelines.” This is important, because not all clinical practices can be rigorously supported by evidence.

Consensus statements are arrived at through an iterative voting process known as the Delphi model. For a consensus statement to be included in any CHEST guideline, a level of 80% consensus is necessary, stated Dr Oulette. Guideline statements are also phrased in such a way that compliance with recommendations can be monitored. The ability to monitor is critical to implementing quality improvement programs.

Literature is monitored continuously by the ACCP, and future ACCP guidelines will not be published in journals, but will be available at websites and updated continuously. According to Dr Oulette, “There will be a Web page for each of the guidelines with links to supportive text and supportive evidence tables....These are living guidelines.”