Medical groups released the nation’s first treatment guidelines for pulmonary hypertension. The guidelines reflected experts’ repeated requests to update details for pulmonary arterial hypertension (PAH).

Doctors have pointed out that PAH therapies have not been used well even though drug companies have developed them sufficiently. The three-year survival rate of Korean patients with PAH is 54.3 percent, much lower than that of Japan at 96 percent.

Medical professionals spoke in one voice that doctors needed an aggressive combination treatment to raise the PAH survival rate. The Korea Academy of Tuberculosis and Respiratory Diseases (KATRD) and the Korean Society of Cardiology (KSC) reflected their opinions in the latest treatment guidelines.

The key to treating PAH based on the newest guidelines is to use sequential combination therapy or to use two or more drugs in different classes in the initial stage, experts said.

Sequential combination therapy, widely used in both research and clinical settings, is a method of consecutively adding drugs in different mechanisms of action when the clinical outcome is inappropriate or worsens with a monotherapy.

The treatment guidelines recommended four sequential combination therapies first.

For PAH patients in the WHO Functional Class 2 and 3, doctors are recommended to add macitentan to sildenafil, add riociguat to bosentan, or add selexipag to endothelin receptor antagonist or phosphodiesterase-5 inhibitor, according to the guidelines. For those in the WHO Functional Class 3, physicians should use epoprostenol with sildenafil.

However, the guidelines alerted caution when adding riociguat to sildenafil or another phosphodiesterase-5 inhibitor. There is Level 3 evidence or general consent that such therapy or procedure is not useful or effective, and it may be even harmful in some cases, the guidelines said.

For rapid combination therapy in the early stage, the guidelines set the ambrisentan-tadalafil combo as the Level 1 recommendation with evidence Level B for PAH patients in the WHO Functional Class 2 and 3.

Early rapid combination therapy aims to improve a severely ill patient’s prognosis through aggressive combination treatment instead of a step-by-step approach.

The ambrisentan-tadalafil combo recommendation was based on the results of a randomized controlled study that met the primary endpoint (reduction of time to clinical failure or mortality from all causes).

In PAH patients in the WHO Functional Class 2 and 3, the study compared ambrisentan alone, tadalafil alone, and their combo. The results showed that patients treated with combo therapy had a 50 percent reduction in clinical failures, including death, hospitalization, PAH progression, and unsatisfactory clinical status.

Professor Lee Jae-seung of pulmonology and critical care medicine at Asan Medical Center, who was one of the writers of the treatment guidelines, said the recommendation for early combination therapy was the essence of the latest guidelines.

“Major international guidelines recommend early combination treatment. But in Korea, early combination therapy is not covered by health insurance. So, many patients fail to get the treatment sufficiently,” Lee said.

Although local physicians referenced foreign guidelines, the latest guidelines are the nation’s first that added domestic data and reflected international standards, he noted. It is also meaningful that many related societies, including KATRD and KSC, approved the guidelines, Lee added.