Goal-oriented Sequential Combo Therapy Benefits PAH Patients, Study Says

José Lopes, PhD avatar

by José Lopes, PhD |

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Opsumit and PAH

Use of sequential combination therapy focused on changes in exercise capacity improves health-related quality of life (HRQoL) in patients with newly diagnosed pulmonary arterial hypertension (PAH), according to a new study.

The research, “Medium-term health-related quality of life in patients with pulmonary arterial hypertension treated with goal-oriented sequential combination therapy based on exercise capacity,” was published in the journal Health and Quality of Life Outcomes.

Combination treatments in PAH patients have led to greater benefits in exercise capacity and risk of clinical worsening than standalone therapies. Still, the optimal combination approach for these patients remains unclear.

Addressing the impact of PAH treatment on HRQoL has been drawing increasing attention, with HRQoL scores being associated with disease prognosis. However, information on changes in quality of life in newly diagnosed patients undergoing goal-oriented sequential combination therapy remains scarce.

A research team from Japan addressed this knowledge gap by focusing on exercise capacity. They conducted a study at Nagoya University Hospital, from October 2012 through March 2015, which included 30 patients (22 of whom were women), mean age of 57 years, with newly diagnosed PAH and mild to severe physical limitation (World Health Organization (WHO) functional classes 2 to 4).

Two patients died during the study, one due to right heart failure at four months and the other to cardiac sudden death at seven months.

During the study period, all patients received tailored treatment designed to achieve a main goal of a peak VO2 — pulmonary oxygen uptake — greater than 15.0 mL/min/kg. This value has been associated with better prognosis, and a peak systolic blood pressure during exercise above 120 mmHg.

As first-line treatment, the patients received an endothelin receptor antagonist (ERA), either bosentan (sold under the brand name Tracleer) or ambrisentan (with the brand name Letairis). If with this approach the patient was sill able to achieved that targeted goal, they would switch to a second line of treatment, which included the addition of a phosphodiesterase-5 inhibitor (PDE-5I), either sildenafil (brand name Revatio) or tadalafil (marketed as Adcirca and ALYQ). If needed, epoprostenol (with brand names Flolan and Veletri) could also be added to the treatment regimen.

All patients underwent cardiac catheterization when they were first diagnosed and 12 months afterward, as well as cardiopulmonary exercise testing, laboratory measurements, and echocardiograms. They also completed the Japanese version of the Short Form (SF)-8 survey of HRQoL at the beginning of the study and at three, six, and 12 months.

At six months, 79% of the patients were taking both ERA and PDE-5 inhibitor, while at 12 months 82% were receiving the combo treatment. Compared with baseline, brain natriuretic peptide (BNP) — a biomarker of cardiovascular diseases — and the tricuspid regurgitation pressure gradient — used to determine pulmonary artery pressure — gradually dropped throughout the 12-month follow-up period.

In contrast, exercise capacity, assessed through the 6-minute walk distance (6MWD) test, significantly increased at three months, with no further improvements at six and 12 months. Peak VO2 was significantly higher at six months, while mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) — an indicator of PAH severity — were lower at 12 months.

Sequential combination therapy gradually improved seven of the eight SF-8 domains, including general health perception, physical functioning, bodily pain, vitality, and mental health.

In general, the participants showed better physical health scores at three months, which remained stable during 12 months. In turn, mental health scores were found to be improved at six months.

Poorer physical health scores were found to be significantly correlated with higher PVR, plasma BNP level, and peak VO2, while mental health scores were significantly associated with only peak VO2. In turn, better social functioning was significantly linked with lower plasma BNP and higher peak VO2.

Although cautioning that the study had a limited number of participants and a short follow-up period, the team believes that “goal-oriented sequential combination therapy based on exercise capacity improves HRQoL in patients with PAH.”