Monotherapy or Combo Therapy for Older Patients With PAH and Multiple Comorbidities?

Patients with pulmonary arterial hypertension (PAH) who have comorbidities or advanced age who are treated with a monotherapy have comparable outcomes to patients on combination therapies.

For patients with pulmonary arterial hypertension (PAH), combination therapy is the gold standard for treatment. A German study found that patients with PAH who have comorbidities or advanced age who are treated with a monotherapy have comparable outcomes to patients on combination therapies.

The findings were published in BMC Pulmonary Medicine.

The researchers noted that patients in studies that support the use of combination therapy “do not necessarily represent the entire spectrum of patients” who are treated at pulmonary hypertension (PH) centers or in PAH registries. Patients in trials tend to be younger with fewer comorbidities and cardiovascular risk factors.

“Comparative studies of these different patient groups indicate that PAH combination therapy in elderly patients with multiple cardiovascular risk factors (so-called ‘atypical’ PAH patients) may be associated with a higher rate of side effects and reduced efficacy,” they noted. “Hence, these ‘atypical’ patients, when assigned to the low- or intermediate-risk group, might be treated with monotherapy.”

The authors sought to understand the proportion of patients with PAH treated with monotherapy, which patients with PAH are receiving monotherapy, and what the outcomes looked like for these patients on monotherapy.

The study evaluated 131 patients with PAH treated at 4 German PH centers between 2026 and 2018. The patients were categorized as “typical” or “atypical.” Patients who were considered “atypical” were older than 65 years and had at least 3 of the following: arterial hypertension, coronary heart disease, diabetes, obesity (body mass index > 30 kg/m2), diastolic dysfunction (by echocardiography), or atrial fibrillation.

The majority (65.6%) of patients were considered typical (n = 86) and 34.4% were classified as atypical (n = 45). There were significant differences between the 2 groups for age, sex, diastolic dysfunction, arterial hypertension, coronary heart disease, atrial fibrillation, diabetes, chronic kidney disease, and peak oxygen uptake.

At baseline, 117 patients were being treated with PAH therapy, of whom 70.9% were receiving monotherapy and 29.1% received dual or triple therapy. At the first follow-up, the number of patients receiving therapy had increased to 125; the proportion of patients continuing to receive monotherapy dropped to 57.6%, while patients on dual or triple therapy increased to 42.4%. At the second follow-up, 111 patients were on therapy, with 45.0% on monotherapy and 55.0% on dual or triple therapy.

Over time, the proportion of atypical patients on combination therapy increased. As age increased, the proportion of patients treated with combination therapy decreased.

The researchers found no significant difference (P = .411) in survival among patients prescribed monotherapy vs combination therapy. At 12 months, the survival rate was 89% among atypical patients and 85% among typical patients (P = .700). Survival at 12 months did not differ among atypical patients on combination vs monotherapy.

“Considering these results, upfront combination therapy for ‘atypical’ PAH patients may not be needed when PAH is complicated by advanced age and multiple comorbidities, since the outcome of monotherapy in these patients appears to be comparable to that of dual or triple therapy in ‘typical’ PAH patients,” the authors concluded.


Stubbe B, Seyfarth H-J, Kleymann J, et al. Monotherapy in patients with pulmonary arterial hypertension at four German PH centres. BMC Pulm Med. 2021;21(1):130. doi:10.1186/s12890-021-01499-2

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